Your SlideShare is downloading. ×
Cuidadomdicoendiabetes 2009-091110224108-phpapp01
Upcoming SlideShare
Loading in...5

Thanks for flagging this SlideShare!

Oops! An error has occurred.

Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

Cuidadomdicoendiabetes 2009-091110224108-phpapp01


Published on

Published in: Health & Medicine

  • Be the first to comment

  • Be the first to like this

No Downloads
Total Views
On Slideshare
From Embeds
Number of Embeds
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

No notes for slide


  • 1. Standards of Medical Care in Diabetes—2009AMERICAN DIABETES ASSOCIATIONDiabetes is a chronic illness that re-quires continuing medical careand patient self-management ed-ucation to prevent acute complicationsand to reduce the risk of long-termcomplications. Diabetes care is complexand requires that many issues, beyondglycemic control, be addressed. A largebody of evidence exists that supports arange of interventions to improve dia-betes outcomes.These standards of care are in-tended to provide clinicians, patients,researchers, payors, and other inter-ested individuals with the componentsof diabetes care, treatment goals, andtools to evaluate the quality of care.While individual preferences, comor-bidities, and other patient factors mayrequire modification of goals, targetsthat are desirable for most patients withdiabetes are provided. These standardsare not intended to preclude more ex-tensive evaluation and management ofthe patient by other specialists asneeded. For more detailed information,refer to references 1–3.The recommendations included arescreening, diagnostic, and therapeuticactions that are known or believed tofavorably affect health outcomes of pa-tients with diabetes. A grading system(Table 1), developed by the AmericanDiabetes Association (ADA) and mod-eled after existing methods, was utilizedto clarify and codify the evidence thatforms the basis for the recommenda-tions. The level of evidence that sup-ports each recommendation is listedafter each recommendation using theletters A, B, C, or E.I. CLASSIFICATION ANDDIAGNOSISA. ClassificationIn 1997, ADA issued new diagnostic andclassification criteria (4); in 2003, modi-fications were made regarding the diagno-sis of impaired fasting glucose (5). Theclassification of diabetes includes fourclinical classes:● type 1 diabetes (results from ␤-cell de-struction, usually leading to absoluteinsulin deficiency)● type 2 diabetes (results from a progres-sive insulin secretory defect on thebackground of insulin resistance)● other specific types of diabetes due toother causes, e.g., genetic defects in␤-cell function, genetic defects in insu-lin action, diseases of the exocrine pan-creas (such as cystic fibrosis), and drug-or chemical-induced (such as in thetreatment of AIDS or after organ trans-plantation)● gestational diabetes mellitus (GDM)(diabetes diagnosed during pregnancy)Some patients cannot be clearly classified astype 1 or type 2 diabetes. Clinical presenta-tion and disease progression vary consider-ably in both types of diabetes. Occasionally,patientswhootherwisehavetype2diabetesmay present with ketoacidosis. Similarly,patients with type 1 may have a late onsetand slow (but relentless) progression of dis-ease despite having features of autoimmunedisease. Such difficulties in diagnosis mayoccur in children, adolescents, and adults.The true diagnosis may become more obvi-ous over time.B. Diagnosis of diabetesCurrent criteria for the diagnosis of diabetesinnonpregnantadultsareshowninTable2.Three ways to diagnose diabetes are recom-mended at the time of this statement, andeach must be confirmed on a subsequentday unless unequivocal symptoms of hy-perglycemia are present. Although the 75-goral glucose tolerance test (OGTT) is moresensitive and modestly more specific thanthe fasting plasma glucose (FPG) to diag-nose diabetes, it is poorly reproducible anddifficult to perform in practice. Because ofease of use, acceptability to patients, andlower cost, the FPG has been the preferreddiagnostic test. Though FPG is less sensitivethan the OGTT, the vast majority of peoplewho do not meet diagnostic criteria for dia-betes by FPG but would by OGTT will havean A1C value well under 7.0% (6).Though the OGTT is not recom-mended for routine clinical use, it may beuseful for further evaluation of patients inwhom diabetes is still strongly suspectedbut who have normal FPG or IFG (seeSection I.C).The use of the A1C for the diagnosisof diabetes has previously not been rec-ommended due to lack of global stan-dardization and uncertainty aboutdiagnostic thresholds. However, with aworld-wide move toward a standardizedassay and with increasing observationalevidence about the prognostic signifi-cance of A1C, an Expert Committee onthe Diagnosis of Diabetes was convenedin 2008. This joint committee of ADA, theEuropean Association for the Study of Di-abetes, and the International DiabetesFederation will likely recommend that theA1C become the preferred diagnostic testfor diabetes. Diagnostic cut-points are be-ing discussed at the time of publication ofthis statement. Updated recommenda-tions will be published in Diabetes Careand will be available at Diagnosis of pre-diabetesHyperglycemia not sufficient to meet thediagnostic criteria for diabetes is catego-● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●The recommendations in this article are based on the evidence reviewed in the following publication:Standards of Care for Diabetes (Technical Review). Diabetes Care 17:1514–1522, 1994.Originally approved 1988. Most recent review/revision October 2008.DOI: 10.2337/dc09-S013© 2009 by the American Diabetes Association. Readers may use this article as long as the work is properlycited, the use is educational and not for profit, and the work is not altered. See for details.P O S I T I O N S T A T E M E N TDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S13
  • 2. rized as either impaired fasting glucose(IFG) or impaired glucose tolerance(IGT), depending on whether it is identi-fied through the FPG or the OGTT:● IFG ϭ FPG 100 mg/dl (5.6 mmol/l) to125 mg/dl (6.9 mmol/l)● IGT ϭ 2-h plasma glucose 140 mg/dl(7.8 mmol/l) to 199 mg/dl (11.0mmol/l)IFG and IGT have been officially termed“pre-diabetes.” Both categories of pre-diabetes are risk factors for future diabetesand for cardiovascular disease (CVD) (7).II. TESTING FOR PRE-DIABETES AND DIABETESIN ASYMPTOMATICPATIENTSRecommendations● Testing to detect pre-diabetes and type2 diabetes in asymptomatic peopleshould be considered in adults of anyage who are overweight or obese (BMIՆ25 kg/m2) and who have one or moreadditional risk factors for diabetes (Ta-ble 3). In those without these risk fac-tors, testing should begin at age 45years. (B)● If tests are normal, repeat testing shouldbe carried out at least at 3-year inter-vals. (E)● To test for pre-diabetes or diabetes, anFPG test or 2-h OGTT (75-g glucoseload) or both are appropriate. (B)● An OGTT may be considered in pa-tients with IFG to better define the riskof diabetes. (E)● In those identified with pre-diabetes,identify and, if appropriate, treat otherCVD risk factors. (B)For many illnesses, there is a major dis-tinction between screening and diagnos-tic testing. However, for diabetes, thesame tests would be used for “screening”as for diagnosis. Type 2 diabetes has along asymptomatic phase and significantclinical risk markers. Diabetes may beidentified anywhere along a spectrum ofclinical scenarios ranging from a seem-ingly low-risk individual who happens tohave glucose testing, to a higher-risk in-dividual whom the provider tests becauseof high suspicion of diabetes, to the symp-tomatic patient. The discussion herein isprimarily framed as testing for diabetes inthose without symptoms. Testing for dia-betes will also detect individuals with pre-diabetes.A. Testing for pre-diabetes and type2 diabetes in adultsType 2 diabetes is frequently not diag-nosed until complications appear, andapproximately one-third of all peoplewith diabetes may be undiagnosed. Al-though the effectiveness of early identifi-cation of pre-diabetes and diabetesthrough mass testing of asymptomatic in-dividuals has not been definitively proven(and rigorous trials to provide such proofare unlikely to occur), pre-diabetes anddiabetes meet established criteria for con-ditions in which early detection is appro-priate. Both conditions are common,increasing in prevalence, and impose sig-nificant public health burdens. There is along presymptomatic phase before the di-agnosis of type 2 diabetes is usually made.Relatively simple tests are available to de-tect preclinical disease (8). Additionally,the duration of glycemic burden is astrong predictor of adverse outcomes,and effective interventions exist to pre-vent progression of pre-diabetes to diabe-tes (see Section IV) and to reduce risk ofcomplications of diabetes (see SectionVI).Recommendations for testing for pre-Table 1—ADA evidence grading system for clinical practice recommendationsLevel ofevidence DescriptionA Clear evidence from well-conducted, generalizable, randomized controlledtrials that are adequately powered, including:● Evidence from a well-conducted multicenter trial● Evidence from a meta-analysis that incorporated quality ratings in theanalysisCompelling nonexperimental evidence, i.e., “all or none” rule developedby the Centre for Evidence-Based Medicine at OxfordSupportive evidence from well-conducted randomized controlled trialsthat are adequately powered, including:● Evidence from a well-conducted trial at one or more institutions● Evidence from a meta-analysis that incorporated quality ratings in theanalysisB Supportive evidence from well-conducted cohort studies, including:● Evidence from a well-conducted prospective cohort study or registry● Evidence from a well-conducted meta-analysis of cohort studiesSupportive evidence from a well-conducted case-control studyC Supportive evidence from poorly controlled or uncontrolled studies● Evidence from randomized clinical trials with one or more major orthree or more minor methodological flaws that could invalidate theresults● Evidence from observational studies with high potential for bias (suchas case series with comparison to historical controls)● Evidence from case series or case reportsConflicting evidence with the weight of evidence supporting therecommendationE Expert consensus or clinical experienceTable 2—Criteria for the diagnosis of diabetes1. FPG Ն126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for atleast 8 h.*OR2. Symptoms of hyperglycemia and a casual (random) plasma glucose Ն200mg/dl (11.1 mmol/l). Casual (random) is defined as any time of day withoutregard to time since last meal. The classic symptoms of hyperglycemiainclude polyuria, polydipsia, and unexplained weight loss.OR3. 2-h plasma glucose Ն200 mg/dl (11.1 mmol/l) during an OGTT. The testshould be performed as described by the World Health Organization usinga glucose load containing the equivalent of 75-g anhydrous glucosedissolved in water.**In the absence of unequivocal hyperglycemia, these criteria should be confirmed by repeat testing on adifferent day (5).Standards of Medical CareS14 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 3. diabetes and diabetes in asymptomatic,undiagnosed adults are listed in Table 3.Testing should be considered in adults ofany age with BMI Ն25 kg/m2and one ormore risk factors for diabetes. Because ageis a major risk factor for diabetes, testingof those without other risk factors shouldbegin no later than age 45 years.Either FPG testing or the 2-h OGTT isappropriate for testing. The 2-h OGTTidentifies people with either IFG or IGT,and thus, more pre-diabetic people at in-creased risk for the development of dia-betes and CVD. It should be noted thatthe two tests do not necessarily detect thesame pre-diabetic individuals (9). The ef-ficacy of interventions for primary pre-vention of type 2 diabetes (10–16) hasprimarily been demonstrated among in-dividuals with IGT, not individuals withIFG (who do not also have IGT). As notedin the diagnosis section (Section I.B), theFPG test is more convenient, more repro-ducible, less costly, and easier to admin-ister than the 2-h OGTT (4,5). An OGTTmay be useful in patients with IFG to bet-ter define the risk of diabetes.The appropriate interval betweentests is not known (17). The rationale forthe 3-year interval is that false-negativeswill be repeated before substantial timeelapses, and there is little likelihood thatan individual will develop significantcomplications of diabetes within 3 yearsof a negative test result.Because of the need for follow-up anddiscussion of abnormal results, testingshould be carried out within the healthcare setting. Community screening out-side a health care setting is not recom-mended because people with positivetests may not seek, or have access to, ap-propriate follow-up testing and care.Conversely, there may be failure to ensureappropriate repeat testing for individualswho test negative. Community screeningmay also be poorly targeted, i.e., it mayfail to reach the groups most at risk andinappropriately test those at low risk (theworried well) or even those already diag-nosed (18,19).B. Testing for type 2 diabetes inchildrenThe incidence of type 2 diabetes in ado-lescents has increased dramatically in thelast decade, especially in minority popu-lations (20), although the disease remainsrare in the general adolescent population(21). Consistent with recommendationsfor adults, children and youth at in-creased risk for the presence or the devel-opment of type 2 diabetes should betested within the health care setting (22).The recommendations of the ADA con-sensus statement on type 2 diabetes inchildren and youth, with some modifica-tions, are summarized in Table 4.C. Screening for type 1 diabetesGenerally, people with type 1 diabetespresent with acute symptoms of diabetesand markedly elevated blood glucose lev-els, and most cases are diagnosed soonafter the onset of hyperglycemia. How-ever, evidence from type 1 preventionstudies suggests that measurement of isletautoantibodies identifies individuals whoare at risk for developing type 1 diabetes.Such testing may be appropriate in high-risk individuals, such as those with priortransient hyperglycemia or those who haverelatives with type 1 diabetes, in the contextof clinical research studies (see, for exam-ple, clinical testing of asymptom-atic low-risk individuals cannot currentlybe recommended, as it would identify veryfew individuals in the general populationwhoareatrisk.Individualswhoscreenpos-itive should be counseled about their risk ofdeveloping diabetes. Clinical studies are be-ing conducted to test various methods ofpreventing type 1 diabetes, or reversingearly type 1 diabetes, in those with evidenceof autoimmunity.III. DETECTION ANDDIAGNOSIS OF GDMRecommendations● Screen for GDM using risk factor anal-ysis and, if appropriate, use of anOGTT. (C)● Women with GDM should be screenedfor diabetes 6–12 weeks postpartumand should be followed up with subse-quent screening for the development ofdiabetes or pre-diabetes. (E)GDM is defined as any degree of glucoseintolerance with onset or first recognitionduring pregnancy (4). Although mostcases resolve with delivery, the definitionapplies whether or not the condition per-sists after pregnancy and does not excludethe possibility that unrecognized glucoseintolerance may have antedated or begunconcomitantly with the pregnancy. Ap-Table 3—Criteria for testing for pre-diabetes and diabetes in asymptomatic adult individuals1. Testing should be considered in all adults who are overweight (BMI Ն25 kg/m2*) andhave additional risk factors:● physical inactivity● first-degree relative with diabetes● members of a high-risk ethnic population (e.g., African American, Latino, NativeAmerican, Asian American, Pacific Islander)● women who delivered a baby weighing Ͼ9 lb or were diagnosed with GDM● hypertension (Ն140/90 mmHg or on therapy for hypertension)● HDL cholesterol level Ͻ35 mg/dl (0.90 mmol/l) and/or a triglyceride level Ͼ250mg/dl (2.82 mmol/l)● women with polycystic ovarian syndrome (PCOS)● IGT or IFG on previous testing● other clinical conditions associated with insulin resistance (e.g., severe obesity,acanthosis nigricans)● history of CVD2. In the absence of the above criteria, testing for pre-diabetes and diabetes should beginat age 45 years3. If results are normal, testing should be repeated at least at 3-year intervals, withconsideration of more frequent testing depending on initial results and risk status.*At-risk BMI may be lower in some ethnic groups.Table 4—Testing for type 2 diabetes inasymptomatic childrenCriteria:● Overweight (BMI Ͼ85th percentile forage and sex, weight for height Ͼ85thpercentile, or weight Ͼ120% of ideal forheight)Plus any two of the following risk factors:● Family history of type 2 diabetes in first-or second-degree relative● Race/ethnicity (Native American, AfricanAmerican, Latino, Asian American, PacificIslander)● Signs of insulin resistance or conditionsassociated with insulin resistance(acanthosis nigricans, hypertension,dyslipidemia, PCOS, or small-for-gestational-age birthweight)● Maternal history of diabetes or GDMduring the child’s gestationAge of initiation: age 10 years or at onset ofpuberty, if puberty occurs at a youngerageFrequency: every 3 yearsTest: FPG preferredPosition StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S15
  • 4. proximately 7% of all pregnancies (rang-ing from 1 to 14% depending on thepopulation studied and the diagnostictests employed) are complicated by GDM,resulting in more than 200,000 casesannually.Because of the risks of GDM to themother and neonate, screening and di-agnosis are warranted. The screeningand diagnostic strategies, based on the2004 ADA position statement on gesta-tional diabetes mellitus (23), are outlined inTable 5.Results of the Hyperglycemia and Ad-verse Pregnancy Outcomes study (24), alarge-scale (including ϳ25,000 pregnantwomen) multinational epidemiologicstudy, demonstrated that risk of adversematernal, fetal, and neonatal outcomescontinuously increased as a function ofmaternal glycemia at 24–28 weeks, evenwithin ranges previously considered nor-mal for pregnancy. For most complica-tions, there was no threshold for risk.These results have led to careful reconsid-eration of the diagnostic criteria for GDM.An international group representing mul-tiple obstetrical and diabetes organiza-tions, including ADA, is currentlyworking on consensus toward 1) a world-wide standard for which diagnostic test touse for GDM and 2) rational diagnosticcut points.Because women with a history ofGDM have a greatly increased subse-quent risk for diabetes (25), they shouldbe screened for diabetes 6–12 weekspostpartum, using nonpregnant OGTTcriteria, and should be followed up withsubsequent screening for the develop-ment of diabetes or pre-diabetes, as out-lined in Section II. For information onthe National Diabetes Education Pro-gram (NDEP) campaign to prevent type2 diabetes in women with GDM, go PREVENTION/DELAYOF TYPE 2 DIABETESRecommendations● Patients with IGT (A) or IFG (E) shouldbe referred to an effective ongoing sup-port program for weight loss of 5–10%of body weight and for increasing phys-ical activity to at least 150 min per weekof moderate activity such as walking.● Follow-up counseling appears to be im-portant for success. (B)● Based on potential cost savings of dia-betes prevention, such counselingshould be covered by third-party pay-ors. (E)● In addition to lifestyle counseling, met-formin may be considered in those whoare at very high risk for developing di-abetes (combined IFG and IGT plusother risk factors such as A1C Ͼ6%,hypertension, low HDL cholesterol, el-evated triglycerides, or family history ofdiabetes in a first-degree relative) andwho are obese and under 60 years ofage. (E)● Monitoring for the development of di-abetes in those with pre-diabetesshould be performed every year. (E)Randomized controlled trials have shownthat individuals at high risk for develop-ing diabetes (those with IFG, IGT, orboth) can be given interventions that sig-nificantly decrease the rate of onset of di-abetes (10 –16). These interventionsinclude intensive lifestyle modificationprograms that have been shown to be veryeffective (Ն58% reduction after 3 years)and use of the pharmacologic agents met-formin, acarbose, orlistat, and thiazo-lidinediones (TZDs), each of which hasbeen shown to decrease incident diabetesto various degrees. A summary of majordiabetes prevention trials is shown in Ta-ble 6.Two studies of lifestyle interventionhave shown persistent reduction in therate of conversion to type 2 diabetes with3 (26) to 14 years (27) of postinterventionfollow-up.Based on the results of clinical trialsand the known risks of progression ofpre-diabetes to diabetes, an ADA Consen-sus Development Panel (7) concludedthat persons with pre-diabetes (IGTand/or IFG) should be counseled on life-style changes with goals similar to those ofthe Diabetes Prevention Program (DPP)(5–10% weight loss and moderate physi-cal activity of ϳ30 min per day). Regard-ing the more difficult issue of drugTable 5—Screening for and diagnosis of GDMCarry out GDM risk assessment at the first prenatal visit.Women at very high risk for GDM should be screened for diabetes as soon as possible afterthe confirmation of pregnancy. Criteria for very high risk are:● severe obesity● prior history of GDM or delivery of large-for-gestational-age infant● presence of glycosuria● diagnosis of PCOS● strong family history of type 2 diabetesScreening/diagnosis at this stage of pregnancy should use standard diagnostic testing (Table 2).All women of greater than low risk of GDM, including those above not found to havediabetes early in pregnancy, should undergo GDM testing at 24–28 weeks of gestation.Low risk status, which does not require GDM screening, is defined as women with ALL ofthe following characteristics:● age Ͻ25 years● weight normal before pregnancy● member of an ethnic group with a low prevalence of diabetes● no known diabetes in first-degree relatives● no history of abnormal glucose tolerance● no history of poor obstetrical outcomeTwo approaches may be followed for GDM screening at 24–28 weeks:1. Two-step approach:A. Perform initial screening by measuring plasma or serum glucose 1 h after a 50-g oralglucose load. A glucose threshold after 50-g load of Ն140 mg/dl identifies ϳ80% ofwomen with GDM, while the sensitivity is further increased to ϳ90% by a threshold ofՆ130 mg/dl.B. Perform a diagnostic 100-g OGTT on a separate day in women who exceed thechosen threshold on 50-g screening.2. One-step approach (may be preferred in clinics with high prevalence of GDM): Performa diagnostic 100-g OGTT in all women to be tested at 24–28 weeks.The 100-g OGTT should be performed in the morning after an overnight fast of at least 8 h.To make a diagnosis of GDM, at least two of the following plasma glucose values must be found:Fasting: Ն95 mg/dl1 h: Ն180 mg/dl2 h: Ն155 mg/dl3 h: Ն140 mg/dlStandards of Medical CareS16 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 5. therapy for diabetes prevention, the con-sensus panel felt that metformin shouldbe the only drug considered for use indiabetes prevention. For other drugs, theissues of cost, side effects, and lack of per-sistence of effect in some studies led thepanel to not recommend their use for di-abetes prevention. Metformin use wasrecommended only for very-high-risk in-dividuals (those with combined IGT andIFG who are obese and under 60 years ofage with at least one other risk factor fordiabetes). In addition, the panel high-lighted the evidence that in the DPP, met-formin was most effective compared tolifestyle in those with BMI of at least 35kg/m2and those under age 60 years.V. DIABETES CAREA. Initial evaluationA complete medical evaluation should beperformed to classify the diabetes, detectthe presence of diabetes complications,review previous treatment and glycemiccontrol in patients with established diabe-tes, assist in formulating a managementplan, and provide a basis for continuingcare. Laboratory tests appropriate to theevaluation of each patient’s medical con-dition should be performed. A focus onthe components of comprehensive care(Table 7) will assist the health care team toensure optimal management of the pa-tient with diabetes.B. ManagementPeople with diabetes should receive med-ical care from a physician-coordinatedteam. Such teams may include, but arenot limited to, physicians, nurse practitio-ners, physician’s assistants, nurses, dieti-tians, pharmacists, and mental healthprofessionals with expertise and a specialinterest in diabetes. It is essential in thiscollaborative and integrated team ap-proach that individuals with diabetes as-sume an active role in their care.The management plan should be for-mulated as an individualized therapeuticalliance among the patient and family, thephysician, and other members of thehealth care team. A variety of strategiesand techniques should be used to provideadequate education and development ofproblem-solving skills in the various as-pects of diabetes management. Imple-mentation of the management planrequires that each aspect is understoodand agreed on by the patient and the careproviders and that the goals and treat-ment plan are reasonable. Any planshould recognize diabetes self-manage-ment education (DSME) as an integralcomponent of care. In developing theplan, consideration should be given to thepatient’s age, school or work scheduleand conditions, physical activity, eatingpatterns, social situation and personality,cultural factors, and presence of compli-cations of diabetes or other medical con-ditions.C. Glycemic control1. Assessment of glycemic controlTwo primary techniques are available forhealth providers and patients to assess theeffectiveness of the management plan onglycemic control: patient self-monitoringof blood glucose (SMBG) or of interstitialglucose and measurement of A1C.a. Glucose monitoringRecommendations● SMBG should be carried out three ormore times daily for patients using mul-tiple insulin injections or insulin pumptherapy. (A)● For patients using less frequent insulininjections, noninsulin therapies, ormedical nutrition therapy (MNT) andphysical activity alone, SMBG may beuseful as a guide to the success of ther-apy. (E)● To achieve postprandial glucose tar-gets, postprandial SMBG may be appro-priate. (E)Table 6—Therapies proven effective in diabetes prevention trialsStudy (ref.) n PopulationMeanage(years)Duration(years)Intervention(daily dose)Conversion incontrol subjects(%/year) Relative riskLifestyleFinnish DPS (11) 522 IGT, BMI Ն25 kg/m255 3.2 Individualdiet/exercise6 0.42 (0.30–0.70)DPP (10) 2,161* IGT, BMI Ն24 kg/m2,FPG Ͼ5.3 mmol/l51 3 Individualdiet/exercise10 0.42 (0.34–0.52)Da Qing (12) 259* IGT (randomizedgroups)45 6 Group diet/exercise 16 0.62 (0.44–0.86)Toranomon study (28) 458 IGT (men), BMI ϭ 24kg/m255 4 Individualdiet/exercise2 0.33 (0.10–1.0)†Indian DPP (16) 269* IGT 46 2.5 Individualdiet/exercise22 0.71 (0.63–0.79)MedicationsDPP (10) 2,155* IGT, BMI Ͼ24 kg/m2,FPG Ͼ5.3 mmol/l51 2.8 Metformin (1,700 mg) 10 0.69 (0.57–0.83)Indian DPP (16) 269* IGT 46 2.5 Metformin (500 mg) 22 0.74 (0.65–0.81)STOP NIDDM (14) 1,419 IGT, FPG Ͼ5.6 mmol/l 54 3.2 Acarbose (300 mg) 13 0.75 (0.63–0.90)XENDOS (29) 3,277 BMI Ͼ30 kg/m243 4 Orlistat (360 mg) 2 0.63 (0.46–0.86)DREAM (15) 5,269 IGT or IFG 55 3.0 Rosiglitazone (8 mg) 9 0.40 (0.35–0.46)*Number of participants in the indicated comparisons, not necessarily in the entire study. †Calculated from information in the article. DPP, Diabetes PreventionProgram; DREAM, Diabetes REduction Assessment with ramipril and rosiglitazone Medication; DPS, Diabetes Prevention Study; STOP NIDDM, Study to PreventNon-Insulin Dependent Diabetes; XENDOS, Xenical in the prevention of Diabetes in Obese Subjects. This table has been reprinted with permission (30) with somemodification.Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S17
  • 6. ● When prescribing SMBG, ensure thatpatients receive initial instruction in,and routine follow-up evaluation of,SMBG technique and their ability to usedata to adjust therapy. (E)● Continuous glucose monitoring (CGM)in conjunction with intensive insulinregimens can be a useful tool to lowerA1C in selected adults (age Ն25 years)with type 1 diabetes (A).● Although the evidence for A1C loweringis less strong in children, teens, andyounger adults, CGM may be helpful inthese groups. Success correlates with ad-herence to ongoing use of the device. (C)● CGM may be a supplemental tool toSMBG in those with hypoglycemia un-awareness and/or frequent hypoglyce-mic episodes. (E)The ADA’s consensus and position state-ments on SMBG provide a comprehensivereview of the subject (31,32). Major clin-ical trials of insulin-treated patients thatdemonstrated the benefits of intensiveglycemic control on diabetes complica-tions have included SMBG as part of mul-tifactorial interventions, suggesting thatSMBG is a component of effective ther-apy. SMBG allows patients to evaluatetheir individual response to therapy andassess whether glycemic targets are beingachieved. Results of SMBG can be usefulin preventing hypoglycemia and adjust-ing medications (particularly prandial in-sulin doses), MNT, and physical activity.The frequency and timing of SMBGshould be dictated by the particular needsand goals of the patients. SMBG is espe-cially important for patients treated withinsulin to monitor for and prevent asymp-tomatic hypoglycemia and hyperglyce-mia. For most patients with type 1diabetes and pregnant women taking in-sulin, SMBG is recommended three ormore times daily. For this population, sig-nificantly more frequent testing may berequired to reach A1C targets safely with-out hypoglycemia. The optimal frequencyand timing of SMBG for patients with type2 diabetes on noninsulin therapy is un-clear. A meta-analysis of SMBG in non–insulin-treated patients with type 2diabetes concluded that some regimen ofSMBG was associated with a reduction inA1C of Ն0.4%. However, many of thestudies in this analysis also included pa-tient education with diet and exercisecounseling and, in some cases, pharma-cologic intervention, making it difficult toassess the contribution of SMBG alone toimproved control (33). Several recent tri-als have called into question the clinicalutility and cost-effectiveness of routineSMBG in non–insulin-treated patients(34–36).BecausetheaccuracyofSMBGisinstru-ment and user dependent (37), it is impor-tant to evaluate each patient’s monitoringtechnique, both initially and at regular in-tervals thereafter. In addition, optimal useof SMBG requires proper interpretation ofthe data. Patients should be taught how touse the data to adjust food intake, exercise,or pharmacological therapy to achieve spe-cific glycemic goals, and these skills shouldbe reevaluated periodically.CGM through the measurement of in-terstitial glucose (which correlates wellwith plasma glucose) is available. Thesesensors require calibration with SMBG,and the latter are still recommended formaking acute treatment decisions. CGMdevices also have alarms for hypo- andhyperglycemic excursions. Small studiesin selected patients with type 1 diabeteshave suggested that CGM use reduces thetime spent in hypo- and hyperglycemicranges and may modestly improve glyce-mic control. A larger 26-week random-ized trial of 322 type 1 patients showedthat adults age 25 years and older usingTable 7—Components of the comprehensive diabetes evaluationMedical history● age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding)● eating patterns, physical activity habits, nutritional status, and weight history; growthand development in children and adolescents● diabetes education history● review of previous treatment regimens and response to therapy (A1C records)● current treatment of diabetes, including medications, meal plan, physical activitypatterns, and results of glucose monitoring and patient’s use of data● DKA frequency, severity, and cause● hypoglycemic episodes● hypoglycemia awareness● any severe hypoglycemia: frequency and cause● history of diabetes-related complications● microvascular: retinopathy, nephropathy, neuropathy (sensory, including history offoot lesions; autonomic, including sexual dysfunction and gastroparesis)● macrovascular: CHD, cerebrovascular disease, PAD● other: psychosocial problems,* dental disease*Physical examination● height, weight, BMI● blood pressure determination, including orthostatic measurements when indicated● fundoscopic examination*● thyroid palpation● skin examination (for acanthosis nigricans and insulin injection sites)● comprehensive foot examination:● inspection● palpation of dorsalis pedis and posterior tibial pulses● presence/absence of patellar and Achilles reflexes● determination of proprioception, vibration, and monofilament sensationLaboratory evaluation● A1C, if results not available within past 2–3 monthsIf not performed/available within past year:● fasting lipid profile, including total, LDL- and HDL-cholesterol and triglycerides● liver function tests● test for urine albumin excretion with spot urine albumin/creatinine ratio● serum creatinine and calculated GFR● thyroid-stimulating hormone in type 1 diabetes, dyslipidemia or women over age 50Referrals● annual dilated eye exam● family planning for women of reproductive age● registered dietitian for MNT● diabetes self-management education● dental examination● mental Health professional, if needed*See appropriate referrals for these categories.Standards of Medical CareS18 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 7. intensive insulin therapy and CGM expe-rienced a 0.5% reduction in A1C (fromϳ7.6 to 7.1%) compared with usual in-tensive insulin therapy with SMBG (38).Sensor use in children, teens, and adultsto age 24 years did not result in significantA1C lowering, and there was no signifi-cant difference in hypoglycemia in anygroup. Importantly, the greatest predictorof A1C lowering in this study for all age-groups was frequency of sensor use,which was lower in younger age-groups.Although CGM is an evolving technology,emerging data suggest that, in appropri-ately selected patients who are motivatedto wear it most of the time, it may offerbenefit. CGM may be particularly usefulin those with hypoglycemia unawarenessand/or frequent episodes of hypoglyce-mia, and studies in this area are ongoing.b. A1CRecommendations● Perform the A1C test at least two timesa year in patients who are meeting treat-ment goals (and who have stable glyce-mic control). (E)● Perform the A1C test quarterly in pa-tients whose therapy has changed orwho are not meeting glycemic goals. (E)● Use of point-of-care testing for A1C al-lows for timely decisions on therapychanges, when needed. (E)Because A1C is thought to reflect averageglycemia over several months (37), andhas strong predictive value for diabetescomplications (10,39), A1C testingshould be performed routinely in all pa-tients with diabetes at initial assessmentand then as part of continuing care. Mea-surement approximately every 3 monthsdetermines whether a patient’s glycemictargets have been reached and main-tained. For any individual patient, the fre-quency of A1C testing should bedependent on the clinical situation, thetreatment regimen used, and the judg-ment of the clinician. Some patients withstable glycemia well within target may dowell with testing only twice per year,while unstable or highly intensively man-aged patients (e.g., pregnant type 1women) may be tested more frequentlythan every 3 months. The availability ofthe A1C result at the time that the patientis seen (point-of-care testing) has been re-ported to result in increased intensifica-tion of therapy and improvement inglycemic control (40,41).The A1C test is subject to certain lim-itations. Conditions that affect erythro-cyte turnover (hemolysis, blood loss) andhemoglobin variants must be considered,particularly when the A1C result does notcorrelate with the patient’s clinical situa-tion (37). In addition, A1C does not pro-vide a measure of glycemic variability orhypoglycemia. For patients prone to gly-cemic variability (especially type 1 pa-tients, or type 2 patients with severeinsulin deficiency), glycemic control isbest judged by the combination of resultsof SMBG testing and the A1C. The A1Cmay also serve as a check on the accuracyof the patient’s meter (or the patient’s re-ported SMBG results) and the adequacy ofthe SMBG testing schedule.Table 8 contains the correlation be-tween A1C levels and mean plasma glu-cose levels based on data from theinternational A1C-Derived Average Glu-cose (ADAG) trial utilizing frequentSMBG and continuous glucose monitor-ing in 507 adults (83% Caucasian) withtype 1, type 2, and no diabetes (49) TheADA and American Association of Clini-cal Chemists have determined that thecorrelation (r ϭ 0.92) is strong enough tojustify reporting both an A1C result andan estimated average glucose (eAG) resultwhen a clinician orders the A1C test. Thetable in previous versions of the Stan-dards of Medical Care in Diabetes describ-ing the correlation between A1C andmean glucose was derived from relativelysparse data (one seven-point profile over1 day per A1C reading) in the primarilyCaucasian type 1 participants in the Dia-betes Control and Complications Trial(DCCT) trial (43). Clinicians should notethat the numbers in the table are now dif-ferent, as they are based on ϳ2,800 read-ings per A1C in the ADAG trial.In the ADAG study, there were no sig-nificant differences among racial and eth-nic groups in the regression lines betweenA1C and mean glucose, although therewas a trend toward a difference betweenAfrican/African-American and Caucasianparticipants’ regression lines that mighthave been significant had more African/African-American participants been stud-ied. A recent study comparing A1C toCGM data in 48 type 1 children found ahighly statistically significant correlationbetween A1C and mean blood glucose,although the correlation (r ϭ 0.7) was sig-nificantly lower than in the ADAG trial(44). Whether there are significant differ-ences in how A1C relates to average glu-cose in children or in African-Americanpatients is an area for further study. Forthe time being, the question has not led todifferent recommendations about testingA1C or to different interpretations of theclinical meaning of given levels of A1C inthose populations.For patients in whom A1C/eAG andmeasured blood glucose appear discrep-ant, clinicians should consider the possi-bilities of hemoglobinopathy or alteredred cell turnover and the options of morefrequent and/or different timing of SMBGor use of CGM. Other measures of chronicglycemia such as fructosamine are avail-able, but their linkage to average glucoseand their prognostic significance are notas clear as is the case for A1C.2. Glycemic goals in adults● Lowering A1C to below or around 7%has been shown to reduce microvascu-lar and neuropathic complications oftype 1 and type 2 diabetes. Therefore,for microvascular disease prevention,the A1C goal for nonpregnant adults ingeneral is Ͻ7%. (A)● In type 1 and type 2 diabetes, random-ized controlled trials of intensive versusstandard glycemic control have notshown a significant reduction in CVDoutcomes during the randomized por-tion of the trials. Long-term follow-upof the DCCT and UK Prospective Dia-betes Study (UKPDS) cohorts suggeststhat treatment to A1C targets below oraround 7% in the years soon after thediagnosis of diabetes is associated withlong-term reduction in risk of macro-vascular disease. Until more evidencebecomes available, the general goal ofϽ7% appears reasonable for manyTable 8—Correlation of A1C with averageglucoseA1C (%)Mean plasma glucosemg/dl mmol/l6 126 7.07 154 8.68 183 10.29 212 11.810 240 13.411 269 14.912 298 16.5Estimates based on ADAG data of ϳ2,700 glucosemeasurements over 3 months per A1C measure-ment in 507 adults with type 1, type 2, and no dia-betes. Correlation between A1C and averageglucose: 0.92 (42). A calculator for converting A1Cresults into eAG, in either mg/dl or mmol/l, is avail-able at StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S19
  • 8. adults for macrovascular risk reduc-tion. (B)● Subgroup analyses of clinical trials suchas the DCCT and UKPDS and the mi-crovascular evidence from the Action inDiabetes and Vascular Disease: Preteraxand Diamicron MR Controlled Evalua-tion (ADVANCE) trial suggest a smallbut incremental benefit in microvascu-lar outcomes with A1C values closer tonormal. Therefore, for selected individ-ual patients, providers might reason-ably suggest even lower A1C goals thanthe general goal of Ͻ7%, if this can beachieved without significant hypogly-cemia or other adverse effects of treat-ment. Such patients might includethose with short duration of diabetes,long life expectancy, and no significantCVD. (B)● Conversely, less stringent A1C goalsthan the general goal of Ͻ7% may beappropriate for patients with a historyof severe hypoglycemia, limited life ex-pectancy, advanced microvascular ormacrovascular complications, exten-sive comorbid conditions, and thosewith longstanding diabetes in whomthe general goal is difficult to attain de-spite DSME, appropriate glucose mon-itoring, and effective doses of multipleglucose-lowering agents including in-sulin. (C)Glycemic control is fundamental to themanagement of diabetes. The DCCT, aprospective, randomized, controlled trialof intensive versus standard glycemiccontrol in patients with relatively recentlydiagnosed type 1 diabetes, showed defin-itively that improved glycemic control isassociated with significantly decreasedrates of microvascular (retinopathy andnephropathy) as well as neuropathiccomplications (45). Follow-up of theDCCT cohorts in the Epidemiology of Di-abetes Interventions and Complications(EDIC) study has shown persistence ofthis effect in previously intensivelytreated subjects, even though their glyce-mic control has been equivalent to that ofprevious standard arm subjects duringfollow-up (46,47).In type 2 diabetes, the Kumamotostudy (48) and the UKPDS (49,50) dem-onstrated significant reductions in micro-vascular and neuropathic complicationswith intensive therapy. Similar to theDCCT-EDIC findings, long-term fol-low-up of the UKPDS cohort has recentlydemonstrated a “legacy effect” of early in-tensive glycemic control on long-termrates of microvascular complications,even with loss of glycemic separation be-tween the intensive and standard cohortsafter the end of the randomized con-trolled (51).In each of these large randomizedprospective clinical trials, treatment regi-mens that reduced average A1C to Ն7%(Ն1% above the upper limits of normal)were associated with fewer long-term mi-crovascular complications; however, in-tensive control was found to increase therisk of severe hypoglycemia, most notablyin the DCCT, and led to weight gain(39,52).Epidemiological analyses of theDCCT and UKPDS (39,45) demonstrate acurvilinear relationship between A1C andmicrovascular complications. Such anal-yses suggest that, on a population level,the greatest number of complications willbe averted by taking patients from verypoor control to fair or good control. Theseanalyses also suggest that further loweringof A1C from 7 to 6% is associated withfurther reduction in the risk of microvas-cular complications, albeit the absoluterisk reductions become much smaller.Given the substantially increased risk ofhypoglycemia (particularly in those withtype 1 diabetes) and the relatively muchgreater effort required to achieve near-normoglycemia, the risks of lower targetsmay outweigh the potential benefits onmicrovascular complications on a popu-lation level. However, selected individualpatients, especially those with little co-morbidity and long life expectancy (whomay reap the benefits of further loweringof glycemia below 7%) may, at patientand provider judgment, adopt glycemictargets as close to normal as possible aslong as significant hypoglycemia does notbecome a barrier.Whereas many epidemiologic studiesand meta-analyses (53,54) have clearlyshown a direct relationship between A1Cand CVD, the potential of intensive glyce-mic control to reduce CVD has been lessclearly defined. In the DCCT, there was atrend toward lower risk of CVD eventswith intensive control (risk reduction41%, 95% CI 10–68%), but the numberof events was small. However, 9-yearpost-DCCT follow-up of the cohort hasshown that participants previously ran-domized to the intensive arm had a 42%reduction (P ϭ 0.02) in CVD outcomesand a 57% reduction (P ϭ 0.02) in therisk of nonfatal myocardial infarction(MI), stroke, or CVD death comparedwith those previously in the standard arm(55).The UKPDS trial of type 2 diabetesobserved a 16% reduction in cardiovascu-lar complications (combined fatal or non-fatal MI and sudden death) in theintensive glycemic control arm, althoughthis difference was not statistically signif-icant (P ϭ 0.052), and there was no sug-gestion of benefit on other CVD outcomessuch as stroke. In an epidemiologic anal-ysis of the study cohort, a continuous as-sociation was observed, such that forevery percentage point lower median on-study A1C (e.g., 8 to 7%) there was a sta-tistically significant 18% reduction inCVD events, again with no glycemicthreshold. A recent report of 10 years offollow-up of the UKPDS cohort describes,for the participants originally randomizedto intensive glycemic control comparedwith those randomized to conventionalglycemic control, long-term reductions inMI (15% with sulfonylurea or insulin asinitial pharmacotherapy, 33% with met-formin as initial pharmacotherapy, bothstatistically significant) and in all-causemortality (13 and 27%, respectively, bothstatistically significant) (51).Because of ongoing uncertainty re-garding whether intensive glycemic con-trol can reduce the increased risk of CVDevents in people with type 2 diabetes, sev-eral large long-term trials were launchedin the past decade to compare the effectsof intensive versus standard glycemiccontrol on CVD outcomes in relativelyhigh-risk participants with establishedtype 2 diabetes.The Action to Control CardiovascularRisk in Diabetes (ACCORD) study ran-domized 10,251 participants with eitherhistory of a CVD event (ages 40–79 years)or significant CVD risk (ages 55–79) to astrategy of intensive glycemic control (tar-get A1C Ͻ6.0%) or standard glycemiccontrol (A1C target 7.0–7.9%). Investiga-tors used multiple glycemic medicationsin both arms. ACCORD participants wereon average 62 years old and had a meanduration of diabetes of 10 years, with 35%already treated with insulin at baseline.From a baseline median A1C of 8.1%, theintensive arm reached a median A1C of6.4% within 12 months of randomiza-tion, while the standard group reached amedian A1C of 7.5%. Other risk factorswere treated aggressively and equally inboth groups. The intensive glycemic con-trol group had more use of insulin in com-bination with multiple oral agents,significantly more weight gain, and moreStandards of Medical CareS20 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 9. episodes of severe hypoglycemia than thestandard group.In February 2008, the glycemic con-trol study of ACCORD was halted on therecommendation of the study’s data safetymonitoring board due to the finding of anincreased rate of mortality in the intensivearm compared with the standard arm(1.41%/year vs. 1.14%/year; HR 1.22[95% CI 1.01–1.46]), with a similar in-crease in cardiovascular deaths. The pri-mary outcome of ACCORD (MI, stroke,or cardiovascular death) was lower in theintensive glycemic control group due to areduction in nonfatal MI, although thisfinding was not statistically significantwhen the study was terminated (HR 0.90[95% CI 0.78–1.04]; P ϭ 0.16) (56).Exploratory analyses of the mortalityfindings of ACCORD (evaluating vari-ables including weight gain, use of anyspecific drug or drug combination, andhypoglycemia) were reportedly unable toidentify an explanation for the excessmortality in the intensive arm. Prespeci-fied subset analyses showed that partici-pants with no previous CVD event andthose who had a baseline A1C Ͻ8% had astatistically significant reduction in theprimary CVD outcome.The ADVANCE study randomized11,140 participants to a strategy of inten-sive glycemic control (with primary ther-apy being the sulfonylurea gliclizide andadditional medications as needed toachieve a target A1C of Յ6.5%) or to stan-dard therapy (in which any medicationbut gliclizide could be used and the gly-cemic target was according to “localguidelines”). ADVANCE participants(who had to be at least 55 years of agewith either known vascular disease or atleast one other vascular risk factor) wereslightly older and of similar high CVD riskas those in ACCORD. However, they hadan average duration of diabetes 2 yearsshorter, lower baseline A1C (median7.2%), and almost no use of insulin atenrollment. The median A1C levelsachieved in the intensive and standardarms were 6.3 and 7.0%, respectively,and maximal separation between thearms took several years to achieve. Use ofother drugs that favorably impact CVDrisk (aspirin, statins, ACE inhibitors) waslower in ADVANCE than in the ACCORDor Veterans Affairs Diabetes Trial (VADT).The primary outcome of ADVANCEwas a combination of microvascularevents (nephropathy and retinopathy)and major adverse cardiovascular events(MI, stroke, and cardiovascular death).Intensive glycemic control significantlyreduced the primary endpoint (HR 0.90[95% CI 0.82–0.98]; P ϭ 0.01), althoughthis was due to a significant reduction inthe microvascular outcome (0.86 [0.77–0.97], P ϭ 0.01), primarily developmentof macroalbuminuria, with no significantreduction in the macrovascular outcome(0.94 [0.84–1.06]; P ϭ 0.32). There wasno difference in overall or cardiovascularmortality between the intensive and thestandard glycemic control arms (57).The VADT randomized 1,791 partic-ipants with type 2 diabetes uncontrolledon insulin or maximal dose oral agents(median entry A1C 9.4%) to a strategy ofintensive glycemic control (goal A1CϽ6.0%) or standard glycemic control,with a planned A1C separation of at least1.5%. Medication treatment algorithmswere used to achieve the specified glyce-mic goals, with a goal of using similarmedications in both groups. Median A1Clevels of 6.9 and 8.4% were achieved inthe intensive and standard arms, respec-tively, within the first year of the study.Other CVD risk factors were treated ag-gressively and equally in both groups.The primary outcome of the VADTwas a composite of CVD events (MI,stroke, cardiovascular death, revascular-ization, hospitalization for heart failure,and amputation for ischemia). During amean 6-year follow-up period, the cumu-lative primary outcome was nonsignifi-cantly lower in the intensive arm (HR0.87 [95% CI 0.73–1.04]; P ϭ 0.12).There were more CVD deaths in the in-tensive arm than in the standard arm (40vs. 33; sudden deaths 11 vs. 4), but thedifference was not statistically significant.Post hoc subgroup analyses suggestedthat duration of diabetes interacted withrandomization such that participantswith duration of diabetes less than about12 years appeared to have a CVD benefitof intensive glycemic control while thosewith longer duration of disease beforestudy entry had a neutral or even adverseeffect of intensive glycemic control. Otherexploratory analyses suggested that se-vere hypoglycemia within the past 90days was a strong predictor of the primaryoutcome and of CVD mortality (58).The cause of the excess deaths in theintensive glycemic control arm of AC-CORD compared with the standard armhas been difficult to pinpoint. By design ofthe trial, randomization to the intensivearm was associated with or led to manydownstream effects, such as higher ratesof severe hypoglycemia; more frequentuse of insulin, TZDs, other drugs, anddrug combinations; and greater weightgain. Such factors may be associated sta-tistically with the higher mortality rate inthe intensive arm but may not be caus-ative. It is biologically plausible that se-vere hypoglycemia could increase the riskof cardiovascular death in participantswith high underlying CVD risk. Otherplausible mechanisms for the increase inmortality in ACCORD include weightgain, unmeasured drug effects or interac-tions, or the overall “intensity” of the AC-CORD intervention (use of multiple oralglucose-lowering drugs along with multi-ple doses of insulin, frequent therapy ad-justments to push A1C and self-monitored blood glucose to very lowtargets, and an intense effort to aggres-sively reduce A1C by ϳ2% in participantsentering the trial with advanced diabetesand multiple comorbidities).Since the ADVANCE trial did notshow any increase in mortality in the in-tensive glycemic control arm, examiningthe differences between ADVANCE andACCORD supports additional hypothe-ses. ADVANCE participants on averageappeared to have earlier or less advanceddiabetes, with shorter duration by 2–3years and lower A1C at entry despite verylittle use of insulin at baseline. A1C wasalso lowered less and more gradually inthe ADVANCE trial, and there was no sig-nificant weight gain with intensiveglycemic therapy. Although severe hypo-glycemia was defined somewhat differ-ently in the three trials, it appears that thisoccurred in fewer than 3% of intensivelytreated ADVANCE participants for theentire study duration (median 5 years)compared with ϳ16% of intensivelytreated subjects in ACCORD and 21% inVADT.It is likely that the increase in mortal-ity in ACCORD was related to the overalltreatment strategies for intensifying glyce-mic control in the study population, notthe achieved A1C per se. The ADVANCEstudy achieved a median A1C in its inten-sive arm similar to that in the ACCORDstudy, with no increased mortality haz-ard. Thus, the ACCORD mortality find-ings do not imply that patients with type 2diabetes who can easily achieve or main-tain low A1C levels with lifestyle modifi-cations with or without pharmacotherapyare at risk and need to “raise” their A1C.The three trials compared treatmentsto A1C levels in the “flatter” part of theobservational glycemia-CVD risk curves(median A1C of 6.4–6.9% in the inten-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S21
  • 10. sive arms compared with 7.0–8.4% inthe standard arms). Importantly, their re-sults should not be extrapolated to implythat there would be no cardiovascularbenefit of glucose lowering from verypoor control (e.g., A1C Ͼ9%) to goodcontrol (e.g., A1C Ͻ7%).All three trials were carried out in par-ticipants with established diabetes (meanduration 8–11 years) and either knownCVD or multiple risk factors suggestingthe presence of established atherosclero-sis. Subset analyses of the three trials sug-gested a significant benefit of intensiveglycemic control on CVD in participantswith shorter duration of diabetes, lowerA1C at entry, and/or or absence of knownCVD. The DCCT-EDIC study and thelong-term follow-up of the UKPDS cohortboth suggest that intensive glycemic con-trol initiated soon after diagnosis of dia-betes in patients with a lower level of CVDrisk may impart long-term protectionfrom CVD events. As is the case with mi-crovascular complications, it may be thatglycemic control plays a greater role be-fore macrovascular disease is well devel-oped and minimal or no role when it isadvanced.The benefits of intensive glycemiccontrol on microvascular and neuro-pathic complications are well establishedfor both type 1 and type 2 diabetes. TheADVANCE trial has added to that evi-dence base by demonstrating a significantreduction in the risk of new or worseningalbuminuria when A1C was lowered to6.3% compared with standard glycemiccontrol achieving an A1C of 7.0%. Thelack of significant reduction in CVDevents with intensive glycemic control inACCORD, ADVANCE, and VADT shouldnot lead clinicians to abandon the generaltarget of an A1C Ͻ7.0% and thereby dis-count the benefit of good control on whatare serious and debilitating microvascularcomplications.The evidence for a cardiovascularbenefit of intensive glycemic control pri-marily rests on long-term follow-up ofstudy cohorts treated early in the courseof type 1 and type 2 diabetes and subsetanalyses of ACCORD, ADVANCE, andVADT. Conversely, the mortality findingsin ACCORD suggest that the potentialrisks of very intensive glycemic controlmay outweigh its benefits in some pa-tients, such as those with very long dura-tion of diabetes, known history of severehypoglycemia, advanced atherosclerosis,and advanced age/frailty. Certainly, pro-viders should be vigilant in preventing se-vere hypoglycemia in patients withadvanced disease and should not aggres-sively attempt to achieve near-normalA1C levels in patients in whom such atarget cannot be reasonably easily andsafely achieved.Recommended glycemic goals fornonpregnant adults are shown in Table 9.The recommendations are based on thosefor A1C, with listed blood glucose levelsthat appear to correlate with achievementof an A1C of Ͻ7%. The issue of pre- ver-sus postprandial SMBG targets is complex(59). Elevated postchallenge (2-h OGTT)glucose values have been associated withincreased cardiovascular risk indepen-dent of FPG in some epidemiologicalstudies. In diabetic subjects, some surro-gate measures of vascular pathology, suchas endothelial dysfunction, are negativelyaffected by postprandial hyperglycemia(60). It is clear that postprandial hyper-glycemia, like preprandial hyperglyce-mia, contributes to elevated A1C levels,with its relative contribution being higherat A1C levels that are closer to 7%. How-ever, outcome studies have clearly shownA1C to be the primary predictor of com-plications, and landmark glycemic con-trol trials such as the DCCT and UKPDSrelied overwhelmingly on preprandialSMBG. Additionally, a randomized con-trolled trial presented at the 68th Scien-tific Sessions of the American DiabetesAssociation in June 2008 found no CVDbenefit of insulin regimens targeting post-prandial glucose compared with thosetargeting preprandial glucose. A reason-able recommendation for postprandialtesting and targets is that for individualswho have premeal glucose values withintarget but have A1C values above target,monitoring postprandial plasma glucose(PPG) 1–2 h after the start of the meal andtreatment aimed at reducing PPG valuesto Ͻ180 mg/dl may help lower A1C.As noted above, less stringent treat-ment goals may be appropriate for adultswith limited life expectancies or advancedvascular disease. Glycemic goals for chil-dren are provided in Section VII.A.1.a.Severe or frequent hypoglycemia is an ab-solute indication for the modification oftreatment regimens, including settinghigher glycemic goals.Regarding goals for glycemic controlfor women with GDM, recommendationsfrom the Fifth International Workshop-Conference on Gestational Diabetes Mel-litus (61) were to target the followingmaternal capillary glucose concentra-tions:● preprandial: Յ95 mg/dl (5.3 mmol/l)and either● 1-h postmeal: Յ140 mg/dl (7.8 mmol/l)or● 2-h postmeal: Յ120 mg/dl (6.7 mmol/l)For women with preexisting type 1 ortype 2 diabetes who become pregnant, arecent consensus statement (62) recom-mended the following as optimal glyce-mic goals, if they can be achieved withoutexcessive hypoglycemia:● premeal, bedtime, and overnight glu-cose 60–99 mg/dlTable 9—Summary of glycemic recommendations for non-pregnant adults with diabetesA1C Ͻ7.0%*Preprandial capillary plasma glucose 70–130 mg/dl (3.9–7.2 mmol/l)Peak postprandial capillary plasma glucose Ͻ180 mg/dl (Ͻ10.0 mmol/l)Key concepts in setting glycemic goals:● A1C is the primary target for glycemic control.● Goals should be individualized based on:● duration of diabetes● age/life expectancy● comorbid conditions● known CVD or advanced microvascularcomplications● hypoglycemia unawareness● individual patient considerations● More or less stringent glycemic goals may beappropriate for individual patients.● Postprandial glucose may be targeted if A1C goals arenot met despite reaching preprandial glucose goals.*Referenced to a nondiabetic range of 4.0–6.0% using a DCCT-based assay. Postprandial glucose measure-ments should be made 1–2 h after the beginning of the meal, generally peak levels in patients with diabetes.Standards of Medical CareS22 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 11. ● peak postprandial glucose 100–129mg/dl● A1C Ͻ6.0%3. Approach to treatmenta. Therapy for type 1 diabetes. TheDCCT clearly showed that intensive insu-lin therapy (three or more injections perday of insulin or continuous subcutane-ous insulin infusion (CSII, or insulinpump therapy) was a key part of im-proved glycemia and better outcomes(45). At the time of the study, therapy wascarried out with short- and intermediate-acting human insulins. Despite better mi-crovascular outcomes, intensive insulintherapy was associated with a marked in-crease in severe hypoglycemia (62 epi-sodes per 100 patient-years of therapy).Since the time of the DCCT, a number ofrapid-acting and long-acting insulin ana-logs have been developed. These analogswere designed to be more “physiological”in their pharmacokinetics and pharmaco-dynamics and are associated with less hy-poglycemia with equal A1C lowering intype 1 diabetes (63,64).Therefore, recommended therapy fortype 1 diabetes consists of the followingcomponents: 1) use of multiple dose in-sulin injections (3–4 injections per day ofbasal and prandial insulin) or CSII ther-apy; 2) matching of prandial insulin tocarbohydrate intake, premeal blood glu-cose, and anticipated activity; and 3) formany patients (especially if hypoglycemiais a problem), use of insulin analogs.There are excellent reviews available thatguide the initiation and management ofinsulin therapy to achieve desired glyce-mic goals (3,63,65).b. Therapy for type 2 diabetes. The ADAand the European Association for theStudy of Diabetes published a consensusstatement on the approach to manage-ment of hyperglycemia in individualswith type 2 diabetes (66) and recentlypublished an update (67). Highlights ofthis approach are: intervention at the timeof diagnosis with metformin in combina-tion with lifestyle changes (MNT andexercise) and continuing timely augmen-tation of therapy with additional agents(including early initiation of insulin ther-apy) as a means of achieving and main-taining recommended levels of glycemiccontrol (i.e., A1C Ͻ7% for most patients).The overall objective is to achieve andmaintain glycemic control and to changeinterventions when therapeutic goals arenot being met.The algorithm took into account theevidence for A1C-lowering of the individ-ual interventions, their additive effects,and their expense. The precise drugs usedand their exact sequence may not be asimportant as achieving and maintainingglycemic targets safely. Medications notincluded in the consensus algorithm, ow-ing to less glucose-lowering effectiveness,limited clinical data, and/or relative ex-pense, still may be appropriate choices inindividual patients to achieve glycemicgoals. Initiation of insulin at time of diagno-sis is recommended for individuals present-ing with weight loss or other severehyperglycemic symptoms or signs. For a listof currently approved diabetes medica-tions, see MNTGeneral recommendations● Individuals who have pre-diabetes ordiabetes should receive individualizedMNT as needed to achieve treatmentgoals, preferably provided by a regis-tered dietitian familiar with the compo-nents of diabetes MNT. (B)● MNT should be covered by insuranceand other payors. (E)Energy balance, overweight, andobesity● In overweight and obese insulin-resistant individuals, modest weightloss has been shown to reduce insulinresistance. Thus, weight loss is recom-mended for all overweight or obese in-dividuals who have or are at risk fordiabetes. (A)● For weight loss, either low-carbohy-drate or low-fat calorie restricted dietsmay be effective in the short-term (upto 1 year). (A)● For patients on low-carbohydrate diets,monitor lipid profiles, renal function,and protein intake (in those with ne-phropathy) and adjust hypoglycemictherapy as needed. (E)● Physical activity and behavior modifica-tion are important components of weightloss programs and are most helpful inmaintenance of weight loss. (B)Primary prevention of diabetes● Among individuals at high risk for de-veloping type 2 diabetes, structuredprograms that emphasize lifestylechanges that include moderate weightloss (7% body weight) and regularphysical activity (150 min/week), withdietary strategies including reducedcalories and reduced intake of dietaryfat, can reduce the risk for developingdiabetes and are therefore recom-mended. (A)● Individualsathighriskfortype2diabetesshould be encouraged to achieve the U.S.Department of Agriculture recommenda-tion for dietary fiber (14 g fiber/1,000kcal) and foods containing whole grains(one-half of grain intake). (B)Dietary fat intake in diabetesmanagement● Saturated fat intake should be Ͻ7% oftotal calories. (A)● Intakeoftransfatshouldbeminimized.(B)Carbohydrate intake in diabetesmanagement● Monitoring carbohydrate, whether bycarbohydrate counting, exchanges, orexperience-based estimation, remains akey strategy in achieving glycemic con-trol. (A)● For individuals with diabetes, the use ofthe glycemic index and glycemic loadmay provide a modest additional bene-fit for glycemic control over that ob-served when total carbohydrate isconsidered alone. (B)Other nutrition recommendations● Sugar alcohols and nonnutritive sweet-eners are safe when consumed withinthe acceptable daily intake levels estab-lished by the Food and Drug Adminis-tration (FDA). (A)● If adults with diabetes choose to use alco-hol, daily intake should be limited to amoderate amount (one drink per day orless for adult women and two drinks perday or less for adult men). (E)● Routine supplementation with antioxi-dants, such as vitamins E and C andcarotene, is not advised because of lackof evidence of efficacy and concern re-lated to long-term safety. (A)● Benefit from chromium supplementa-tion in people with diabetes or obesityhas not been conclusively demon-strated and, therefore, cannot be rec-ommended. (E)MNT is an integral component of diabetesprevention, management, and self-management education. In addition to itsrole in preventing and controlling diabe-tes, ADA recognizes the importance ofnutrition as an essential component of anoverall healthy lifestyle. A full review ofthe evidence regarding nutrition in pre-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S23
  • 12. venting and controlling diabetes and itscomplications and additional nutrition-related recommendations can be found inthe ADA position statement “NutritionRecommendations and Interventions forDiabetes,” published in 2007 and up-dated for 2008 (68). Achieving nutrition-related goals requires a coordinated teameffort that includes the active involvementof the person with pre-diabetes or diabe-tes. Because of the complexity of nutritionissues, it is recommended that a registereddietitian who is knowledgeable andskilled in implementing nutrition therapyinto diabetes management and educationbe the team member who provides MNT.Clinical trials/outcome studies ofMNT have reported decreases in A1C at3–6 months ranging from 0.25 to 2.9%with higher reductions seen in type 2diabetes of shorter duration. Multiplestudies have demonstrated sustained im-provements in A1C at 12 months andlonger when a registered dietician pro-vided follow-up visits ranging frommonthly to three sessions per year (69–76). Meta-analyses of studies in nondia-betic, free-living subjects report that MNTreduces LDL cholesterol by 15–25 mg/dl(77) or can lower LDL cholesterol by upto 16% (78), while clinical trials support arole for lifestyle modification in treatinghypertension (78,79).Because of the effects of obesity oninsulin resistance, weight loss is an im-portant therapeutic objective for over-weight or obese individuals with pre-diabetes or diabetes (80). Short-termstudies have demonstrated that moderateweight loss (5% of body weight) in sub-jects with type 2 diabetes is associatedwith decreased insulin resistance, im-proved measures of glycemia and lipemia,and reduced blood pressure (81); longer-term studies (52 weeks) showed mixedeffects on A1C in adults with type 2 dia-betes (82–85), and results were con-founded by pharmacologic weight losstherapy. A systematic review of 80 weightloss studies of Ն1 year duration demon-strated that moderate weight lossachieved through diet alone, diet and ex-ercise, and meal replacements can beachieved and maintained over the longterm (4.8–8% weight loss at 12 months)(86). The multifactorial intensive lifestyleintervention employed in the DPP, whichincluded reduced intake of fat and calo-ries, led to weight loss averaging 7% at 6months and maintenance of 5% weightloss at 3 years, associated with a 58% re-duction in incidence of type 2 diabetes(10). Look AHEAD (Action for Health inDiabetes) is a large clinical trial designedto determine whether long-term weightloss will improve glycemia and preventcardiovascular events in subjects withtype 2 diabetes. One-year results of theintensive lifestyle intervention in this trialshow an average of 8.6% weight loss, sig-nificant reduction of A1C, and reductionin several CVD risk factors (87). Whencompleted, the Look AHEAD trial shouldprovide insight into the effects of long-term weight loss on important clinicaloutcomes.The optimal macronutrient distribu-tion of weight loss diets has not been es-tablished. Although low-fat diets havetraditionally been promoted for weightloss, several randomized controlled trialsfound that subjects on low-carbohydratediets (Ͻ130 g/day of carbohydrate) lostmore weight at 6 months than subjects onlow-fat diets (88,89); however, at 1 year,the difference in weight loss between thelow-carbohydrate and low-fat diets wasnot significant, and weight loss was mod-est with both diets. Another study of over-weight women randomized to one of fourdiets showed significantly more weightloss at 12 months with the Atkins low-carbohydrate diet than with higher-carbohydrate diets (90). Changes inserum triglyceride and HDL cholesterolwere more favorable with the low-carbohydrate diets. In one study, thosesubjects with type 2 diabetes demon-strated a greater decrease in A1C with alow-carbohydrate diet than with a low-fatdiet (89). A recent meta-analysis showedthat at 6 months, low-carbohydrate dietswere associated with greater improve-ments in triglyceride and HDL cholesterolconcentrations than low-fat diets; how-ever, LDL cholesterol was significantlyhigher on the low-carbohydrate diets(91). In a 2-year dietary interventionstudy, Mediterranean and low-carbohy-drate diets were found to be effective andsafe alternatives to a low-fat diet forweight reduction in moderately obeseparticipants (85).The recommended dietary allowancefor digestible carbohydrate is 130 g/dayand is based on providing adequate glu-cose as the required fuel for the centralnervous system without reliance on glu-cose production from ingested protein orfat. Although brain fuel needs can be meton lower carbohydrate diets, long-termmetabolic effects of very-low-carbohy-drate diets are unclear, and such dietseliminate many foods that are importantsources of energy, fiber, vitamins, andminerals that are important in dietary pal-atability (92).Although numerous studies have at-tempted to identify the optimal mix ofmacronutrients for meal plans of peoplewith diabetes, it is unlikely that one suchcombination of macronutrients exists.The best mix of carbohydrate, protein,and fat appears to vary depending onindividual circumstances. For those indi-viduals seeking guidance as to macronu-trient distribution in healthy adults, theDietary Reference Intake (DRI) systemmay be helpful (92). It must be clearlyrecognized that regardless of the macro-nutrient mix, total caloric intake must beappropriate for the weight managementgoal. Further, individualization of the ma-cronutrient composition will depend onthe metabolic status of the patient (e.g.,lipid profile, renal function) and/or foodpreferences. Individuals who choose toconsume plant-based diets that are wellplanned and nutritionally adequate (i.e.,vegetarian) may continue, as this can bedone without being deleterious to meta-bolic control (93,94).The primary goal with respect to di-etary fat in individuals with diabetes is tolimit saturated fatty acids, trans fatty ac-ids, and cholesterol intake so as to reducerisk for CVD. Saturated and trans fatty ac-ids are the principal dietary determinantsof plasma LDL cholesterol. There is a lackof evidence on the effects of specific fattyacids on people with diabetes, so the rec-ommended goals are consistent withthose for individuals with CVD (78,95).The FDA has approved five nonnutri-tive sweeteners for use in the U.S.: acesul-fame potassium, aspartame, neotame,saccharin, and sucralose. Before being al-lowed on the market, all underwent rig-orous scrutiny and were shown to be safewhen consumed by the public, includingpeople with diabetes and women duringpregnancy. Reduced calorie sweetenersapproved by the FDA include sugar alco-hols (polyols) such as erythritol, isomalt,lactitol, maltitol, mannitol, sorbitol, xyli-tol, tagatose, and hydrogenated starch hy-drolysates. The use of sugar alcoholsappears to be safe; however, they maycause diarrhea, especially in children.Reimbursement for MNTMNT, when delivered by a registered di-etitian according to nutrition practiceguidelines, is reimbursed as part of theMedicare program as overseen by theCenters for Medicare and Medicaid Ser-Standards of Medical CareS24 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 13. vices (CMS) ( Bariatric surgeryRecommendations● Bariatric surgery should be consideredfor adults with BMI Ն35 kg/m2andtype 2 diabetes, especially if the diabe-tes is difficult to control with lifestyleand pharmacologic therapy. (B)● Patients with type 2 diabetes who haveundergone bariatric surgery need life-long lifestyle support and medicalmonitoring. (E)● Although small trials have shown glyce-micbenefitofbariatricsurgeryinpatientswith type 2 diabetes and BMI of 30–35kg/m2, there is currently insufficient evi-dencetogenerallyrecommendsurgeryinpatientswithBMIϽ35kg/m2outsideofaresearch protocol. (E)● The long-term benefits, cost-effectiveness, and risks of bariatric sur-gery in individuals with type 2 diabetesshould be studied in well-designed ran-domized controlled trials with optimalmedical and lifestyle therapy as thecomparator. (E)Gastric reduction surgery, either gastricbanding or procedures that involve by-passing or transposing sections of thesmall intestine, when part of a compre-hensive team approach, can be an effec-tive weight loss treatment for severeobesity, and national guidelines supportits consideration for people with type 2diabetes who have BMI at or exceeding 35kg/m2. Bariatric surgery has been shownto lead to near or complete normalizationof glycemia in ϳ55–95% of patients withtype 2 diabetes, depending on the surgicalprocedure. A meta-analysis of studies ofbariatric surgery reported that 78% ofindividuals with type 2 diabetes had com-plete “resolution” of diabetes (normaliza-tion of blood glucose levels in the absenceof medications), and that the resolutionrates were sustained in studies that hadfollow-up exceeding 2 years (96). Resolu-tion rates are lowest with procedures thatonly constrict the stomach and higherwith those that bypass portions of thesmall intestine. Additionally, there is in-creasing evidence that intestinal bypassprocedures may have glycemic effects thatare independent of, and additive to, theireffects on weight.A recent randomized controlled trialcompared adjustable gastric banding to“best available” medical and lifestyletherapy in subjects with type 2 diabetesdiagnosed less than 2 years before ran-domization and BMI 30–40 kg/m2(97).In this trial, 73% of surgically treated pa-tients achieved “remission” of their diabe-tes, compared with 13% of those treatedmedically. The latter group lost only 1.7%of body weight, suggesting that their ther-apy was not optimal. Overall, the trial had60 subjects, and only 13 had a BMI under35 kg/m2, making it difficult to generalizethese results widely to diabetic patientswho are less severely obese or with longerduration of diabetes.Bariatric surgery is costly in the shortterm and has some risks. Rates of morbid-ity and mortality directly related to thesurgery have been reduced considerablyin recent years, with 30-day mortalityrates now 0.28%, similar to those of lapa-roscopic cholecystectomy (98). Longer-term concerns include vitamin andmineral deficiencies, osteoporosis, andrare but often severe hypoglycemia frominsulin hypersecretion. Cohort studies at-tempting to match subjects suggest thatthe procedure may reduce longer-termmortality rates (99), and it is reasonable topostulate that there may be recouping ofcosts over the long run. However, studiesof the mechanisms of glycemic improve-ment, long-term benefits and risks, andcost-effectiveness of bariatric surgery inindividuals with type 2 diabetes will re-quire well-designed randomized clinicaltrials, with optimal medical and lifestyletherapy of diabetes and cardiovascularrisk factors as the comparitor.F. DSMERecommendations● People with diabetes should receiveDSME according to national standardswhen their diabetes is diagnosed and asneeded thereafter. (B)● Self-management behavior change isthe key outcome of DSME and shouldbe measured and monitored as part ofcare. (E)● DSME should address psychosocial is-sues, since emotional well-being isstrongly associated with positive diabe-tes outcomes. (C)● DSME should be reimbursed by third-party payors. (E)DSME is an essential element of diabetescare (100–106), and National Standardsfor DSME (107) are based on evidence forits benefits. Education helps people withdiabetes initiate effective self-care whenthey are first diagnosed. Ongoing DSMEalso helps people with diabetes maintaineffective self-management as their diabe-tes presents new challenges and treatmentadvances become available. DSME helpspatients optimize metabolic control, pre-vent and manage complications, andmaximize quality of life in a cost-effectivemanner (108).Since the 1990s, there has been a shiftfrom a didactic approach, with DSME fo-cusing on providing information, to askill-based approach that focuses onhelping those with diabetes make in-formed self-management choices. Care ofdiabetes has shifted to an approach that ismore patient centered and that places theperson with diabetes, and joint decision-making with heath care professionals, atthe center of the care model. Patient-centered care is respectful of and respon-sive to individual patient preferences,needs, and values and ensures that patientvalues guide all decision making (109).Evidence for the benefits of DSMESeveral studies have found that DSME isassociated with improved diabetesknowledge and improved self-care behav-ior (101), improved clinical outcomessuch as lower A1C (102,103,105,106,110), lower self-reported weight (101),and improved quality of life (104). Betteroutcomes were reported for DSME inter-ventions that were longer and includedfollow-up support (101), that were tai-lored to individual needs and preferences(100), and that addressed psychosocial is-sues (100,101,105). Both individual andgroup approaches have been found effec-tive ((111,112). There is increasing evi-dence for the role of a community healthworker in delivering diabetes educationin addition to the core team (113).National standards for DSMEADA-recognized DSME programs havestaff that must be certified diabetes edu-cators or have recent experience in diabe-tes education and management. Thecurriculum of ADA-recognized DSMEprograms must cover all nine areas of di-abetes management, with the assessedneeds of the individual determiningwhich areas are addressed. The ADA Ed-ucation Recognition Program (ERP) is amechanism to ensure diabetes educationprograms meet the national standards andprovide quality diabetes care.Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S25
  • 14. Reimbursement for DSMEDSME, when provided by a program thatmeets ADA ERP standards, is reimbursedas part of the Medicare program as over-seen by the Centers for Medicare andMedicaid Services (CMS) ( Physical activityRecommendations● People with diabetes should be advisedto perform at least 150 min/week ofmoderate-intensity aerobic physical ac-tivity (50 –70% of maximum heartrate). (A)● In the absence of contraindications,people with type 2 diabetes should beencouraged to perform resistance train-ing three times per week. (A)ADA technical reviews on exercise in pa-tients with diabetes have summarized thevalue of exercise in the diabetes manage-ment plan (114,115). Regular exercisehas been shown to improve blood glucosecontrol, reduce cardiovascular risk fac-tors, contribute to weight loss, and im-prove well being. Furthermore, regularexercise may prevent type 2 diabetes inhigh-risk individuals (10–12). Struc-tured exercise interventions of at least 8weeks’ duration have been shown tolower A1C by an average of 0.66% in peo-ple with type 2 diabetes, even with nosignificant change in BMI (116). Higherlevels of exercise intensity are associatedwith greater improvements in A1C and infitness (117).Frequency and type of exerciseThe U.S. Surgeon General’s report (118)recommended that most adults accumu-late at least 30 min of moderate-intensityactivity on most, ideally all, days of theweek. The studies included in the meta-analysis of effects of exercise interventionson glycemic control (116) had a meannumber of sessions per week of 3.4, witha mean of 49 min per session. The DPPlifestyle intervention, which included 150min per week of moderate intensity exer-cise, had a beneficial effect on glycemia inthose with pre-diabetes. Therefore, itseems reasonable to recommend ϳ150min of exercise per week for people withdiabetes.Resistance exercise improves insulinsensitivity to about the same extent as aer-obic exercise (119). Clinical trials haveprovided strong evidence for the A1C-lowering value of resistance training inolder adults with type 2 diabetes(120,121) and for an additive benefit ofcombined aerobic and resistance exercisein adults with type 2 diabetes (122).Evaluation of the diabetic patientbefore recommending an exerciseprogramPrior guidelines suggested that before rec-ommending a program of physical activ-ity, the provider should assess patientswith multiple cardiovascular risk factorsfor coronary artery disease (CAD). As dis-cussed more fully in Section VI.A.5, thearea of screening asymptomatic diabeticpatients for CAD remains unclear, and arecent ADA consensus statement on thisissue concluded that routine screening isnot recommended (123). Providersshould use clinical judgment in this area.Certainly, high-risk patients should beencouraged to start with short periods oflow-intensity exercise and increase the in-tensity and duration slowly.Providers should assess patients forconditions that might contraindicate cer-tain types of exercise or predispose to in-jury, such as uncontrolled hypertension,severe autonomic neuropathy, severe pe-ripheral neuropathy or history of foot le-sions, and advanced retinopathy. Thepatient’s age and previous physical activ-ity level should be considered.Exercise in the presence ofnonoptimal glycemic controlHyperglycemia. When people with type1 diabetes are deprived of insulin for12–48 h and are ketotic, exercise canworsen hyperglycemia and ketosis (124);therefore, vigorous activity should beavoided in the presence of ketosis. How-ever, it is not necessary to postpone exer-cise based simply on hyperglycemia,provided the patient feels well and urineand/or blood ketones are negative.Hypoglycemia. In individuals taking in-sulin and/or insulin secretagogues, phys-ical activity can cause hypoglycemia ifmedication dose or carbohydrate con-sumption is not altered. For individualson these therapies, added carbohydrateshould be ingested if pre-exercise glucoselevels are Ͻ100 mg/dl (5.6 mmol/l)(125,126). Hypoglycemia is rare in dia-betic individuals who are not treated withinsulin or insulin secretagogues, and nopreventive measures for hypoglycemiaare usually advised in these cases.Exercise in the presence of specificlong-term complications of diabetesRetinopathy. In the presence of prolifer-ative diabetic retinopathy (PDR) or severenonproliferative diabetic retinopathy(NPDR), vigorous aerobic or resistanceexercise may be contraindicated becauseof the risk of triggering vitreous hemor-rhage or retinal detachment (127).Peripheral neuropathy. Decreased painsensation in the extremities results in in-creased risk of skin breakdown and infec-tion and of Charcot joint destruction.Therefore, in the presence of severe pe-ripheral neuropathy, it may be best to en-courage non–weight-bearing activitiessuch as swimming, bicycling, or arm ex-ercises (128,129).Autonomic neuropathy. Autonomicneuropathy can increase the risk of exer-cise-induced injury or adverse eventsthrough decreased cardiac responsivenessto exercise, postural hypotension, impairedthermoregulation, impaired night visiondue to impaired papillary reaction, and un-predictable carbohydrate delivery from gas-troparesis predisposing to hypoglycemia(128). Autonomic neuropathy is alsostrongly associated with CVD in peoplewith diabetes (130,131). People with dia-betic autonomic neuropathy should un-dergo cardiac investigation beforebeginning physical activity more intensethan that to which they are accustomed.Albuminuria and nephropathy. Physicalactivity can acutely increase urinary pro-tein excretion. However, there is no evi-dence that vigorous exercise increases therate of progression of diabetic kidney dis-ease and likely no need for any specificexercise restrictions for people with dia-betic kidney disease (132).H. Psychosocial assessment and careRecommendations● Assessment of psychological and socialsituation should be included as an on-going part of the medical managementof diabetes. (E)● Psychosocial screening and follow-upshould include, but is not limited to,attitudes about the illness, expectationsfor medical management and out-comes, affect/mood, general and diabe-tes-related quality of life, resources(financial, social, and emotional), andpsychiatric history. (E)● Screen for psychosocial problems suchas depression, anxiety, eating disor-ders, and cognitive impairment whenStandards of Medical CareS26 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 15. adherence to the medical regimen ispoor. (E)Psychological and social problems can im-pair the individual’s (133–138) or family’s(139) ability to carry out diabetes care tasksand therefore compromise health status.There are opportunities for the clinician toassess psychosocial status in a timely andefficient manner so that referral for appro-priate services can be accomplished.Key opportunities for screening ofpsychosocial status occur at diagnosis,during regularly scheduled managementvisits, during hospitalizations, at discov-ery of complications, or when problemswith glucose control, quality of life, or ad-herence are identified (140). Patients arelikely to exhibit psychological vulnerabil-ity at diagnosis and when their medicalstatus changes, i.e., the end of the honey-moon period, when the need for intensi-fied treatment is evident, and whencomplications are discovered (135,137).Issues known to impact self-management and health outcomes in-clude but are not limited to attitudesabout the illness, expectations for medicalmanagement and outcomes, affect/mood,general and diabetes-related quality oflife, resources (financial, social, and emo-tional) (136), and psychiatric history(137,140,141). Screening tools are avail-able for a number of these areas (142).Indications for referral to a mental healthspecialist familiar with diabetes manage-ment may include gross noncompliancewith medical regimen (by self or others)(141), depression with the possibility ofself-harm (134,143), debilitating anxiety(alone or with depression), indications ofan eating disorder (144), or cognitivefunctioning that significantly impairsjudgment (143). It is preferable to incor-porate psychological assessment andtreatment into routine care rather thanwaiting for identification of a specificproblem or deterioration in psychologicalstatus (142). Although the clinician maynot feel qualified to treat psychologicalproblems, utilizing the patient-providerrelationship as a foundation for furthertreatment can increase the likelihood thatthe patient will accept referral for otherservices. It is important to establish thatemotional well-being is part of diabetesmanagement (140).I. When treatment goals are not metFor a variety of reasons, some people withdiabetes and their health care providersdo not achieve the desired goals of treat-ment (Table 9). Re-thinking the treatmentregimen may require assessment of barri-ers to adherence including income, edu-cational attainment, and competingdemands, including those related to fam-ily responsibilities and family dynamics.Other strategies may include culturallyappropriate and enhanced DSME, co-management with a diabetes team, refer-ral to a medical social worker forassistance with insurance coverage orchange in pharmacological therapy. Initi-ation of or increase in SMBG, utilizationof continuous glucose monitoring, fre-quent contact with the patient, or referralto an endocrinologist may be useful.J. Intercurrent illnessThe stress of illness, trauma, and/or sur-gery frequently aggravates glycemic con-trol and may precipitate diabeticketoacidosis (DKA) or nonketotic hyper-osmolar state, life-threatening conditionsthat require immediate medical care toprevent complications and death (145).Any condition leading to deterioration inglycemic control necessitates more fre-quent monitoring of blood glucose and(in ketosis-prone patients) urine or bloodketones. Marked hyperglycemia requirestemporary adjustment of the treatmentprogram and, if accompanied by ketosis,vomiting, or alteration in level of con-sciousness, immediate interaction withthe diabetes care team. The patient treatedwith noninsulin therapies or MNT alonemay temporarily require insulin. Ade-quate fluid and caloric intake must be as-sured. Infection or dehydration are morelikely to necessitate hospitalization of theperson with diabetes than the personwithout diabetes.The hospitalized patient should betreated by a physician with expertise in themanagement of diabetes. For further infor-mation on management of patients with hy-perglycemia in the hospital, see SectionVIII.A. For further information on manage-ment of DKA or nonketotic hyperosmolarstate,refertotheADApositionstatementonhyperglycemic crises (145).K. HypoglycemiaRecommendations● Glucose (15–20 g) is the preferredtreatment for the conscious individualwith hypoglycemia, although any formof carbohydrate that contains glucosemay be used. If SMBG 15 min aftertreatment shows continued hypoglyce-mia, the treatment should be repeated.Once SMBG glucose returns to normal,the individual should consume a mealor snack to prevent recurrence of hypo-glycemia. (E)● Glucagon should be prescribed for allindividuals at significant risk of severehypoglycemia, and caregivers or familymembers of these individuals should beinstructed in its administration. Gluca-gon administration is not limited tohealth care professionals. (E)● Individuals with hypoglycemia un-awareness or one or more episodes ofsevere hypoglycemia should be advisedto raise their glycemic targets to strictlyavoid further hypoglycemia for at leastseveral weeks to partially reverse hypo-glycemia unawareness and reduce riskof future episodes. (B)Hypoglycemia is the leading limiting fac-tor in the glycemic management of type 1and insulin-treated type 2 diabetes (146).Treatment of hypoglycemia (plasma glu-cose Ͻ70 mg/dl) requires ingestion ofglucose- or carbohydrate-containingfoods. The acute glycemic response cor-relates better with the glucose contentthan with the carbohydrate content of thefood. Although pure glucose is the pre-ferred treatment, any form of carbohy-drate that contains glucose will raiseblood glucose. Added fat may retard andthen prolong the acute glycemic response(147). Ongoing activity of insulin or in-sulin secretagogues may lead to recur-rence of hypoglycemia unless furtherfood is ingested after recovery.Severe hypoglycemia (where the indi-vidual requires the assistance of anotherperson and cannot be treated with oralcarbohydrate due to confusion or uncon-sciousness) should be treated using emer-gency glucagon kits, which require aprescription. Those in close contact with,or having custodial care of, people withhypoglycemia-prone diabetes (familymembers, roommates, school personnel,child care providers, correctional institu-tion staff, or coworkers) should be in-structed in use of such kits. An individualdoes not need to be a health care profes-sional to safely administer glucagon. Careshould be taken to ensure that unexpiredglucagon kits are available.Prevention of hypoglycemia is a crit-ical component of diabetes management.Teaching people with diabetes to balanceinsulin use, carbohydrate intake, and ex-ercise is a necessary but not always suffi-cient strategy. In type 1 diabetes andseverely insulin-deficient type 2 diabetes,Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S27
  • 16. the syndrome of hypoglycemia unaware-ness, or hypoglycemia-associated auto-nomic failure, can severely compromisestringent diabetes control and quality oflife. The deficient counter-regulatory hor-mone release and autonomic responses inthis syndrome are both risk factors for,and caused by, hypoglycemia. A corollaryto this “vicious cycle” is that several weeksof avoidance of hypoglycemia has beendemonstrated to improve counter-regulation and awareness to some extentin many patients (146,148,149). Hence,patients with one or more episodes of se-vere hypoglycemia may benefit from atleast short-term relaxation of glycemictargets.L. ImmunizationRecommendations● Annually provide an influenza vaccine toall diabetic patients Ն6 months of age.(C)● Administer pneumococcal polysaccha-ride vaccine to all diabetic patients Ն2years of age. A one-time revaccination isrecommended for individuals Ͼ64years of age previously immunizedwhen they were Ͻ65 years of age if thevaccine was administered Ͼ5 yearsago. Other indications for repeat vacci-nation include nephrotic syndrome,chronic renal disease, and other immu-nocompromised states, such as aftertransplantation. (C)Influenza and pneumonia are common,preventable infectious diseases associatedwith high mortality and morbidity in theelderly and in people with chronic dis-eases. Though there are limited studiesreporting the morbidity and mortality ofinfluenza and pneumococcal pneumoniaspecifically in people with diabetes, ob-servational studies of patients with a vari-ety of chronic illnesses, includingdiabetes, show that these conditions areassociated with an increase in hospitaliza-tions for influenza and its complications.People with diabetes may be at increasedrisk of the bacteremic form of pneumo-coccal infection and have been reportedto have a high risk of nosocomial bactere-mia, which has a mortality rate as high as50% (150).Safe and effective vaccines are avail-able that can greatly reduce the risk ofserious complications from these diseases(151,152). In a case-control series, influ-enza vaccine was shown to reduce diabe-tes-related hospital admission by as muchas 79% during flu epidemics (151). Thereis sufficient evidence to support that peo-ple with diabetes have appropriate sero-logic and clinical responses to thesevaccinations. The Centers for DiseaseControl and Prevention’s Advisory Com-mittee on Immunization Practices recom-mends influenza and pneumococcalvaccines for all individuals with diabetes( Fora complete discussion on the preventionof influenza and pneumococcal disease inpeople with diabetes, consult the techni-cal review and position statement on thissubject (150,153).VI. PREVENTION ANDMANAGEMENT OFDIABETES COMPLICATIONSA. CVDCVD is the major cause of morbidity andmortality for individuals with diabetesand the largest contributor to the directand indirect costs of diabetes. The com-mon conditions coexisting with type 2diabetes (e.g., hypertension and dyslipi-demia) are clear risk factors for CVD, anddiabetes itself confers independent risk.Numerous studies have shown the effi-cacy of controlling individual cardiovas-cular risk factors in preventing or slowingCVD in people with diabetes. Large ben-efits are seen when multiple risk factorsare addressed globally (154). Evidence issummarized in the following sections andreviewed in detail in the ADA technicalreviews on hypertension (155), dyslipide-mia (156), aspirin therapy (157), andsmoking cessation (158) and in the Amer-ican Heart Association (AHA)/ADA scien-tific statement on prevention of CVD inpeople with diabetes (159).1. Hypertension/blood pressurecontrolRecommendationsScreening and diagnosis● Blood pressure should be measured atevery routine diabetes visit. Patientsfound to have a systolic blood pres-sure of Ն130 mmHg or a diastolicblood pressure of Ն80 mmHg shouldhave blood pressure confirmed on aseparate day. Repeat systolic bloodpressure of Ն130 mmHg or diastolicblood pressure of Ն80 mmHg con-firms a diagnosis of hypertension. (C)Goals● Patients with diabetes should be treatedto a systolic blood pressure Ͻ130mmHg. (C)● Patients with diabetes should be treatedto a diastolic blood pressure Ͻ80mmHg. (B)Treatment● Patients with a systolic blood pressureof 130–139 mmHg or a diastolic bloodpressure of 80–89 mmHg may be givenlifestyle therapy alone for a maximumof 3 months and then, if targets are notachieved, be treated with the additionof pharmacological agents. (E)● Patients with more severe hyperten-sion (systolic blood pressure Ն140mmHg or diastolic blood pressureՆ90 mmHg) at diagnosis or fol-low-up should receive pharmacologictherapy in addition to lifestyle ther-apy. (A)● Pharmacologic therapy for patientswith diabetes and hypertension shouldbe with a regimen that includes eitheran ACE inhibitor or an angiotensin re-ceptor blocker (ARB). If one class is nottolerated, the other should be substi-tuted. If needed to achieve blood pres-sure targets, a thiazide diuretic shouldbe added to those with an estimatedGFR (see below) Ն30 ml/min per 1.73m2and a loop diuretic for those with anestimated GFR Ͻ30 ml/min per 1.73m2. (C)● Multiple drug therapy (two or moreagents at maximal doses) is generally re-quired to achieve blood pressure targets.(B)● If ACE inhibitors, ARBs, or diuretics areused, kidney function and serum potas-sium levels should be closely moni-tored. (E)● In pregnant patients with diabetes andchronic hypertension, blood pressuretarget goals of 110–129/65–79 mmHgare suggested in the interest of long-term maternal health and minimizingimpaired fetal growth. ACE inhibitorsand ARBs are contraindicated duringpregnancy. (E)Hypertension is a common comorbidityof diabetes, affecting the majority of pa-tients, with prevalence depending on typeof diabetes, age, obesity, and ethnicity.Hypertension is a major risk factor forboth CVD and microvascular complica-tions. In type 1 diabetes, hypertension isoften the result of underlying nephropa-Standards of Medical CareS28 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 17. thy, while in type 2 it usually coexistswith other cardiometabolic risk factors.Screening and diagnosisMeasurement of blood pressure in the of-fice should be done by a trained individ-ual and follow the guidelines establishedfor nondiabetic individuals: measure-ment in the seated position, with feet onthe floor and arm supported at heart level,after 5 min of rest. Cuff size should beappropriate for the upper arm circumfer-ence. Elevated values should be con-firmed on a separate day. Because of theclear synergistic risks of hypertension anddiabetes, the diagnostic cutoff for a diag-nosis of hypertension is lower in peoplewith diabetes (blood pressure Ն130/80)than in those without diabetes (bloodpressure Ն140/90 mmHg) (160).Home blood pressure self-monitoringand 24-h ambulatory blood pressuremonitoring may provide additional evi-dence of “white coat” and masked hyper-tension and other discrepancies betweenoffice and “true” blood pressure, andstudies in nondiabetic populations showthat home measurements may bettercorrelate with CVD risk than office mea-surements (161,162). However, the pre-ponderance of the clear evidence ofbenefits of treatment of hypertension inpeople with diabetes is based on officemeasurements.Treatment goalsRandomized clinical trials have demon-strated the benefit (reduction of CHDevents, stroke, and nephropathy) of low-ering blood pressure to Ͻ140 mmHg sys-tolic and Ͻ80 mmHg diastolic inindividuals with diabetes (160,163–165).Epidemiologic analyses show that bloodpressure Ͼ115/75 mmHg is associatedwith increased cardiovascular event ratesand mortality in individuals with diabetes(160,166,167). Therefore, a target bloodpressure goal of Ͻ130/80 mmHg is rea-sonable if it can be safely achieved. Theongoing ACCORD trial is designed to de-termine whether blood pressure loweringto systolic blood pressure Ͻ120 mmHgprovides greater cardiovascular protec-tion than a systolic blood pressure level ofϽ140 mmHg in patients with type 2 dia-betes ( strategiesAlthough there are no well-controlledstudies of diet and exercise in the treat-ment of hypertension in individuals withdiabetes, studies in nondiabetic individu-als have shown anti-hypertensive effectssimilar to pharmacologic monotherapy ofreducing sodium intake and excess bodyweight; increasing consumption of fruits,vegetables, and low-fat dairy products;avoiding excessive alcohol consumption;and increasing activity levels (160,168).These nonpharmacological strategies mayalso positively affect glycemia and lipidcontrol. Their effects on cardiovascularevents have not been established. An ini-tial trial of nonpharmacologic therapymay be reasonable in diabetic individualswith mild hypertension (systolic bloodpressure 130–139 mmHg or diastolicblood pressure 80–89 mmHg). If theblood pressure is Ն140 mmHg systolicand/or Ն90 mmHg diastolic at the time ofdiagnosis, pharmacologic therapy shouldbe initiated along with nonpharmacologictherapy (160).Lowering of blood pressure with reg-imens based on a variety of antihyperten-sive drugs, including ACE inhibitors,ARBs, ␤-blockers, diuretics, and calciumchannel blockers, has been shown to beeffective in reducing cardiovascularevents. Several studies have suggestedthat ACE inhibitors may be superior todihydropyridine calcium channel block-ers in reducing cardiovascular events(169–171). However, a variety of otherstudies have shown no specific advantageto ACE inhibitors as initial treatment ofhypertension in the general hypertensivepopulation, but rather an advantage oncardiovascular outcomes of initial therapywith low-dose thiazide diuretics (160,172,173).In people with diabetes, inhibitors ofthe renin-angiotensin system (RAS) mayhave unique advantages for initial or earlytherapy of hypertension. In a nonhyper-tension trial of high-risk individuals, in-cluding a large subset with diabetes, anACE inhibitor reduced CVD outcomes(174). In patients with congestive heartfailure (CHF), including diabetic sub-groups, ARBs have been shown to reducemajor CVD outcomes (175–178), and intype 2 patients with significant nephrop-athy, ARBs were superior to calciumchannel blockers for reducing heart fail-ure (179–181). Though evidence for dis-tinct advantages of RAS inhibitors onCVD outcomes in diabetes remains con-flicting (163,182), the high CVD risks as-sociated with diabetes, and the highprevalence of undiagnosed CVD, may stillfavor recommendations for their use asfirst-line hypertension therapy in peoplewith diabetes (160). Recently, the bloodpressure arm of the ADVANCE trial dem-onstrated that routine administration of afixed combination of the ACE inhibitorperindopril and the diuretic indapamidesignificantly reduced combined micro-vascular and macrovascular outcomes, aswell as CVD and total mortality. The im-proved outcomes could also have beendue to lower achieved blood pressure inthe perindopril-indapamide arm (183).The compelling benefits of RAS inhibitorsin diabetic patients with albuminuria orrenal insufficiency provide additional ra-tionale for use of these agents (see sectionVI.B below).An important caveat is that most pa-tients with hypertension require multi-drug therapy to reach treatment goals,especially diabetic patients whose targetsare lower. Many patients will requirethree or more drugs to reach target goals(160). If blood pressure is refractory tomultiple agents, clinicians should con-sider an evaluation for secondary forms ofhypertension.During pregnancy in diabetic womenwith chronic hypertension, target bloodpressure goals of systolic blood pressure110 –129 mmHg and diastolic bloodpressure 65–79 mmHg are reasonable, asthey contribute to long-term maternalhealth. Lower blood pressure levels maybe associated with impaired fetal growth.During pregnancy, treatment with ACEinhibitors and ARBs is contraindicated,since they are likely to cause fetal damage.Antihypertensive drugs known to be ef-fective and safe in pregnancy includemethyldopa, labetalol, diltiazem,clonidine, and prazosin. Chronic diureticuse during pregnancy has been associatedwith restricted maternal plasma volume,which might reduce uteroplacental perfu-sion (184).2. Dyslipidemia/lipid managementRecommendationsScreening● In most adult patients, measure fastinglipid profile at least annually. In adultswith low-risk lipid values (LDL choles-terol Ͻ100 mg/dl, HDL cholesterolϾ50 mg/dl, and triglycerides Ͻ150mg/dl), lipid assessments may be re-peated every 2 years. (E)Treatment recommendations and goals● Lifestyle modification focusing on thereduction of saturated fat, trans fat, andcholesterol intake; weight loss (if indi-cated); and increased physical activityPosition StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S29
  • 18. should be recommended to improvethe lipid profile in patients with diabe-tes. (A)● Statin therapy should be added to life-style therapy, regardless of baselinelipid levels, for diabetic patients:● with overt CVD (A)● without CVD who are over the age of40 and have one or more other CVDrisk factors. (A)● For lower-risk patients than the above(e.g., without overt CVD and under theage of 40), statin therapy should beconsidered in addition to lifestyle ther-apy if LDL cholesterol remains above100 mg/dl or in those with multipleCVD risk factors. (E)● In individuals without overt CVD, theprimary goal is an LDL cholesterolϽ100 mg/dl (2.6 mmol/l). (A)● In individuals with overt CVD, a lowerLDL cholesterol goal of Ͻ70 mg/dl (1.8mmol/l), using a high dose of a statin, isan option. (B)● If drug-treated patients do not reach theabove targets on maximal tolerated sta-tin therapy, a reduction in LDL choles-terol of ϳ30–40% from baseline is analternative therapeutic goal. (A)● Triglycerides levels Ͻ150 mg/dl (1.7mmol/l) and HDL cholesterol Ͼ40mg/dl (1.0 mmol/l) in men and Ͼ50mg/dl (1.3 mmol/l) in women are desir-able. However, LDL cholesterol–targeted statin therapy remains thepreferred strategy. (C)● If targets are not reached on maximallytolerated doses of statins, combinationtherapy using statins and other lipid-lowering agents may be considered toachieve lipid targets but has not beenevaluated in outcome studies for eitherCVD outcomes or safety. (E)● Statin therapy is contraindicated inpregnancy. (E)Evidence for benefits of lipid-lowering therapyPatients with type 2 diabetes have an in-creased prevalence of lipid abnormalities,contributing to their high risk of CVD.For the past decade or more, multipleclinical trials demonstrated significant ef-fects of pharmacologic (primarily statin)therapy on CVD outcomes in subjectswith CHD and for primary CVD preven-tion (185). Subanalyses of diabetic sub-groups of larger trials (186–190) andtrials specifically in subjects with diabetes(191,192) showed significant primaryand secondary prevention of CVDevents Ϯ CHD deaths in diabetic popula-tions. As shown in Table 10, and similarto findings in nondiabetic subjects, re-duction in “hard” CVD outcomes (CHDdeath and nonfatal MI) can be moreclearly seen in diabetic subjects with highbaseline CVD risk (known CVD and/orvery high LDL cholesterol levels), butoverall the benefits of statin therapy inpeople with diabetes at moderate or highrisk for CVD are convincing.Low levels of HDL cholesterol, oftenassociated with elevated triglyceride lev-els, are the most prevalent pattern of dys-lipidemia in persons with type 2 diabetes.However, the evidence base for drugs thattarget these lipid fractions is significantlyless robust than that for statin therapy(193). Nicotinic acid has been shown toreduce CVD outcomes (194), althoughthe study was done in a nondiabetic co-hort. Gemfibrozil has been shown to de-crease rates of CVD events in subjectswithout diabetes (195,196) and in the di-abetic subgroup in one of the larger trials(195). However, in a large trial specific todiabetic patients, fenofibrate failed to re-duce overall cardiovascular outcomes(197).Dyslipidemia treatment and targetlipid levelsFor most patients with diabetes, the firstpriority of dyslipidemia therapy (unlesssevere hypertriglyceridemia is the imme-diate issue) is to lower LDL cholesterol toa target goal of Ͻ100 mg/dl (2.60 mmol/l)(198). Lifestyle intervention, includingMNT, increased physical activity, weightloss, and smoking cessation, may allowTable 11—Summary of recommendations for glycemic, blood pressure, and lipid control foradults with diabetesA1C Ͻ7.0%*Blood pressure Ͻ130/80 mmHgLipidsLDL cholesterol Ͻ100 mg/dl (Ͻ2.6 mmol/l)†*Referenced to a nondiabetic range of 4.0–6.0% using a DCCT-based assay. †In individuals with overt CVD,a lower LDL cholesterol goal of Ͻ70 mg/dl (1.8 mmol/l), using a high dose of a statin, is an option.Table 10—Reduction in 10-year risk of major CVD end points (CHD death/non-fatal MI) in major statin trials, or substudies of major trials,in diabetic subjects (n ‫؍‬ 16,032)Study (ref.)CVDprevention Statin dose and comparatorRisk reduction(%)Relative riskreduction(%)Absolute riskreduction(%)LDL cholesterolreduction4S-DM (186) 2° Simvastatin 20–40 mg vs. placebo 85.7 to 43.2 50 42.5 186 to 119 mg/dl (36%)ASPEN 2° (191) 2° Atorvastatin 10 mg vs. placebo 39.5 to 24.5 34 12.7 112 to 79 mg/dl (29%)HPS-DM (187) 2° Simvastatin 40 mg vs. placebo 43.8 to 36.3 17 7.5 123 to 84 mg/dl (31%)CARE-DM (188) 2° Pravastatin 40 mg vs. placebo 40.8 to 35.4 13 5.4 136 to 99 mg/dl (27%)TNT-DM (189) 2° Atorvastatin 80 mg vs. 10 mg 26.3 to 21.6 18 4.7 99 to 77 mg/dl (22%)HPS-DM (187) 1° Simvastatin 40 mg vs. placebo 17.5 to 11.5 34 6.0 124 to 86 mg/dl (31%)CARDS (209) 1° Atorvastatin 10 mg vs. placebo 11.5 to 7.5 35 4 118 to 71 mg/dl (40%)ASPEN (191) 1° Atorvastatin 10 mg vs. placebo 9.8 to 7.9 19 1.9 114 to 80 mg/dl (30%)ASCOT-DM (190) 1° Atorvastatin 10 mg vs. placebo 11.1 to 10.2 8 0.9 125 to 82 mg/dl (34%)Studies were of differing lengths (3.3–5.4 years) and used somewhat different outcomes, but all reported rates of CVD death and non-fatal MI. In this tabulation,results of the statin on 10-year risk of major CVD end points (CHD death/non-fatal MI) are listed for comparison between studies. Correlation between 10-year CVDrisk of the control group and the absolute risk reduction with statin therapy is highly significant (P ϭ 0.0007). Analyses provided by Craig Williams, Pharm.D.,Oregon Health & Science University, 2007.Standards of Medical CareS30 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 19. some patients to reach lipid goals. Nutri-tion intervention should be tailored ac-cording to each patient’s age, type ofdiabetes, pharmacological treatment,lipid levels, and other medical conditionsand should focus on the reduction of sat-urated fat, cholesterol, and trans unsatur-ated fat intake. Glycemic control can alsobeneficially modify plasma lipid levels,particularly in patients with very hightriglycerides and poor glycemic control.In those with clinical CVD or over age40 with other CVD risk factors, pharma-cological treatment should be added tolifestyle therapy regardless of baselinelipid levels. Statins are the drugs of choicefor LDL cholesterol lowering.In patients other than those describedabove, statin treatment should be consid-ered if there is an inadequate LDL choles-terol response to lifestyle modificationsand improved glucose control, or if thepatient has increased cardiovascular risk(e.g., multiple cardiovascular risk factorsor long duration of diabetes). Very littleclinical trial evidence exists for type 2 pa-tients under the age of 40, or for type 1patients of any age. In the Heart Protec-tion Study, the subgroup of 600 patientswith type 1 diabetes (lower age limit 40years) had a proportionately similarreduction in risk as patients with type 2diabetes, although not statistically signif-icant (187). Although the data are not de-finitive, consideration should be given tosimilar lipid-lowering goals in type 1 dia-betic patients as those in type 2 diabeticpatients, particularly if they have othercardiovascular risk factors.Alternative LDL cholesterol goalsVirtually all trials of statins and CVD out-comes have tested specific doses of statinsagainst placebo, other doses of statin, orother statins, rather than aiming for spe-cific LDL cholesterol goals (199). As canbe seen in Table 10, placebo-controlledtrials generally achieved LDL cholesterolreductions of 30–40% from baseline.Hence, LDL cholesterol lowering of thismagnitude is an acceptable outcome forpatients who cannot reach LDL choles-terol goals due to severe baseline eleva-tions in LDL cholesterol and/orintolerance of maximal, or any, statindoses. Additionally, for those with base-line LDL cholesterol minimally above 100mg/dl, prescribing statin therapy to lowerLDL cholesterol about 30–40% frombaseline is probably more effective thanprescribing just enough to get LDL cho-lesterol slightly below 100 mg/dl.Recent clinical trials in high-risk pa-tients, such as those with acute coronarysyndromes or previous cardiovascularevents (200–202), have demonstratedthat more aggressive therapy with highdoses of statins to achieve an LDL choles-terol of Ͻ70 mg/dl led to a significant re-duction in further events. Therefore, areduction in LDL cholesterol to a goal ofϽ70 mg/dl is an option in very-high-riskdiabetic patients with overt CVD (203).In individual patients, LDL choles-terol lowering with statins is highly vari-able, and this variable response is poorlyunderstood (204). Reduction of CVDevents with statins correlates very closelywith LDL cholesterol lowering (185).When maximally tolerated doses of st-atins fail to significantly lower LDL cho-lesterol (Ͻ30% reduction from patientsbaseline), the primary aim of combinationtherapy should be to achieve additionalLDL cholesterol lowering. Niacin, fenofi-brate, ezetimibe, and bile acid seques-trants all offer additional LDL cholesterollowering. The evidence that combinationtherapy provides a significant incrementin CVD risk reduction over statin therapyalone is still elusive.Treatment of other lipoproteinfractions or targetsSevere hypertriglyceridemia may warrantimmediate therapy of this abnormalitywith lifestyle and usually pharmacologictherapy (fibric acid derivative or niacin)to reduce the risk of acute pancreatitis. Inthe absence of severe hypertriglyceride-mia, therapy targeting HDL cholesterol ortriglycerides has intuitive appeal but lacksthe evidence base of statin therapy (162).If the HDL cholesterol is Ͻ40 mg/dl andthe LDL cholesterol is between 100 and129 mg/dl, gemfibrozil or niacin might beused, especially if a patient is intolerant tostatins. Niacin is the most effective drugfor raising HDL cholesterol. It can signif-icantly increase blood glucose at highdoses, but recent studies demonstrate thatat modest doses (750–2,000 mg/day),significant improvements in LDL choles-terol, HDL cholesterol, and triglyceridelevels are accompanied by only modestchanges in glucose that are generally ame-nable to adjustment of diabetes therapy(205,206).Combination therapy, with a statinand a fibrate or a statin and niacin, may beefficacious for treatment for all three lipidfractions, but this combination is associ-ated with an increased risk for abnormaltransaminase levels, myositis, or rhabdo-myolysis. The risk of rhabdomyolysis ishigher with higher doses of statins andwith renal insufficiency and seems to belower when statins are combined with fe-nofibrate than gemfibrozil (207). Severalongoing trials may provide much-neededevidence for the effects of combinationtherapy on cardiovascular outcomes.In 2008, a consensus panel convenedby ADA and the American College of Car-diology recommended a greater focus onnon-HDL cholesterol and apolipoproteinB (apo B) in patients who are likely to havesmall LDL particles, such as people withdiabetes (208). The consensus panel sug-gested that for statin-treated patients inwhom the LDL cholesterol goal would beϽ70 mg/dl (non-HDL cholesterol Ͻ100mg/dl), apo B should be measured andtreated to Ͻ80 mg/dl. For patients on st-atins with an LDL cholesterol goal ofϽ100 mg/dl (non-HDL cholesterol Ͻ130mg/dl), apo B should be measured andtreated to below 90 mg/dl.Table 11 summarizes the general rec-ommendations for glycemic, blood pres-sure, and lipid control for adults withdiabetes.3. Antiplatelet agentsRecommendations● Use aspirin therapy (75–162 mg/day)as a primary prevention strategy inthose with type 1 or type 2 diabetes atincreased cardiovascular risk, includ-ing those who are Ͼ40 years of age orwho have additional risk factors (familyhistory of CVD, hypertension, smok-ing, dyslipidemia, or albuminuria). (C)● Use aspirin therapy (75–162 mg/day)as a secondary prevention strategy inthose with diabetes with a history ofCVD. (A)● For patients with CVD and docu-mented aspirin allergy, clopidogrel (75mg/day) should be used. (B)● Combination therapy with ASA (75–162 mg/day) and clopidogrel (75 mg/day) is reasonable for up to a year afteran acute coronary syndrome. (B)● Aspirin therapy is not recommended inpeople under 30 years of age due to lackof evidence of benefit and is contrain-dicated in patients under the age of 21years because of the associated risk ofReye’s syndrome. (E)The use of aspirin in diabetes is reviewedin detail in the ADA technical review(157) and position statement (210) onthis topic. Aspirin has been recom-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S31
  • 20. mended for primary (211,212) andsecondary (213,214) prevention of car-diovascular events in high-risk diabeticand nondiabetic individuals. One largemeta-analysis and several clinical trialsdemonstrate the efficacy of using aspirinas a preventive measure for cardiovascu-lar events, including stroke and myocar-dial infarction. Many trials have shown anϳ30% decrease in myocardial infarctionand a 20% decrease in stroke in a widerange of patients, including young andmiddle-aged patients, patients with andwithout a history of CVD, men andwomen, and patients with hypertension.Dosages used in most clinical trialsranged from 75 to 325 mg/day. There islittle evidence to support any specific dose,but using the lowest possible dosage mayhelpreducesideeffects(215).Conversely,arandomized trial of 100 mg of aspirin dailyshowed less of a primary prevention effect,without statistical significance, in the largediabetic subgroup in contrast to significantbenefit in those without diabetes (216),raising the issue of aspirin resistance inthose with diabetes.The systematic review of evidence forthe U.S. Preventive Services Task Force(USPSTF) estimated that aspirin reducedthe risk for nonfatal and fatal MI (oddsratio 0.72 [95% CI 0.60–0.87]). The re-view acknowledged the low numbers ofdiabetic subjects in most trials but con-cluded that subset analyses and a singletrial in diabetic patients suggested that theestimates extended to those with diabetes(211). The USPSTF stated that the risk-to-benefit ratio favors aspirin use when5-year CHD risk equals or exceeds 3%and suggested aspirin therapy be consid-ered for men Ͼ40 years of age, postmeno-pausal women, and younger persons withCHD risk factors (including diabetes)(212).There is no evidence for a specific ageat which to start aspirin, but aspirin hasnot been studied at ages Ͻ30 years.Clopidogrel has been demonstratedto reduce CVD events in diabetic individ-uals (217). Adjunctive therapy in the firstyear after acute coronary syndrome invery-high-risk patients, or as alternativetherapy in aspirin-intolerant patients,should be considered.4. Smoking cessationRecommendations● Advise all patients not to smoke. (A)● Include smoking cessation counselingand other forms of treatment as a rou-tine component of diabetes care. (B)Issues of smoking in diabetes are reviewedin detail in the ADA technical review (158)and position statement (218) on this topic.A large body of evidence from epidemiolog-ical, case-control, and cohort studies pro-vides convincing documentation of thecausal link between cigarette smoking andhealth risks. Cigarette smoking contributesto one of every five deaths in the U.S. and isthemostimportantmodifiablecauseofpre-mature death. Much of the prior work doc-umenting the impact of smoking on healthdid not separately discuss results on subsetsof individuals with diabetes, suggesting thatthe identified risks are at least equivalent tothose found in the general population.Other studies of individuals with diabetesconsistently found a heightened risk ofCVD and premature death among smokers.Smokingisalsorelatedtotheprematurede-velopment of microvascular complicationsof diabetes and may have a role in the de-velopment of type 2 diabetes.A number of large randomized clini-cal trials have demonstrated the efficacyand cost-effectiveness of smoking cessa-tion counseling in changing smoking be-havior and reducing tobacco use. Theroutine and thorough assessment of to-bacco use is important as a means of pre-venting smoking or encouragingcessation. Special considerations shouldinclude assessment of level of nicotine de-pendence, which is associated with diffi-culty in quitting and relapse (219,220).Free telephone quit lines are available ineach state (see CHD screening and treatmentRecommendationsScreening● In asymptomatic patients, evaluate riskfactors to stratify patients by 10-year risk,and treat risk factors accordingly. (B)Treatment● In patients with known CVD, ACE in-hibitor (C), aspirin (A), and statin ther-apy (A) (if not contraindicated) shouldbe used to reduce the risk of cardiovas-cular events.● In patients with a prior myocardial in-farction, add ␤-blockers (if not contra-indicated) to reduce mortality. (A)● In patients Ͼ40 years of age with an-other cardiovascular risk factor (hyper-tension, family history, dyslipidemia,microalbuminuria, cardiac autonomicneuropathy, or smoking), aspirin andstatin therapy (if not contraindicated)should be used to reduce the risk ofcardiovascular events. (B)● In patients with CHF, TZD use is con-traindicated. (C)● Metformin may be used in patients withstable CHF if renal function is normal.It should be avoided in unstable or hos-pitalized patients with CHF. (C)Screening for CAD is reviewed in a re-cently updated consensus statement(123). To identify the presence of CAD indiabetic patients without clear or sugges-tive symptoms, a risk factor–based ap-proach to the initial diagnostic evaluationand subsequent follow-up has intuitiveappeal. However, recent studies con-cluded that using this approach fails toidentify which patients will have silentischemia on screening tests (130,221).Candidates for cardiac testing includethose with 1) typical or atypical cardiacsymptoms and 2) an abnormal resting elec-trocardiogram (ECG). The screening ofasymptomatic patients remains controver-sial, especially as intensive medical therapyindicated in diabetic patients at high risk forCVD has an increasing evidence base forprovidingequaloutcomestoinvasiverevas-cularization, including in diabetic patients(222). There is also recent preliminary evi-dence that silent myocardial ischemia mayreverse over time, adding to the controversyconcerning aggressive screening strategies(223). Finally, a recent randomized obser-vational trial presented at the ADA’s Scien-tific Sessions in June 2008 demonstrated noclinical benefit to routine screening ofasymptomatic patients with type 2 diabetesand normal ECGs. Despite abnormal myo-cardial perfusion imaging in more than onein five patients, cardiac outcomes were es-sentially equal (and very low) in screenedversus unscreened patients.In all patients with diabetes, cardio-vascular risk factors should be assessed atleast annually. These risk factors includedyslipidemia, hypertension, smoking, apositive family history of premature cor-onary disease, and the presence of micro-or macroalbuminuria. Abnormal risk fac-tors should be treated as described else-where in these guidelines. Patients atincreased CHD risk should receive aspirinand a statin and ACE inhibitor or ARBtherapy if hypertensive, unless there arecontraindications to a particular drugclass. While clear benefit exists for ACEinhibitor and ARB therapy in patientsStandards of Medical CareS32 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 21. with nephropathy or hypertension, thebenefits in patients with CVD in the ab-sence of these conditions is less clear, es-pecially when LDL cholesterol isconcomitantly controlled (224,225)B. Nephropathy screening andtreatmentRecommendationsGeneral recommendations● To reduce the risk or slow the progres-sion of nephropathy, optimize glucosecontrol. (A)● To reduce the risk or slow the progres-sion of nephropathy, optimize bloodpressure control. (A)Screening● Perform an annual test to assess urinealbumin excretion in type 1 diabetic pa-tients with diabetes duration of Ն5years and in all type 2 diabetic patients,starting at diagnosis. (E)● Measure serum creatinine at least annu-ally in all adults with diabetes regard-less of the degree of urine albuminexcretion. The serum creatinine shouldbe used to estimate GFR and stage thelevel of chronic kidney disease (CKD),if present. (E)Treatment● In the treatment of the nonpregnant pa-tient with micro- or macroalbuminuria,either ACE inhibitors or ARBs shouldbe used. (A)● While there are no adequate head-to-head comparisons of ACE inhibitorsand ARBs, there is clinical trial supportfor each of the following statements:● In patients with type 1 diabetes, hy-pertension, and any degree of albu-minuria, ACE inhibitors have beenshown to delay the progression of ne-phropathy. (A)● In patients with type 2 diabetes, hy-pertension, and microalbuminuria,both ACE inhibitors and ARBs havebeen shown to delay the progressionto macroalbuminuria. (A)● In patients with type 2 diabetes, hy-pertension, macroalbuminuria, andrenal insufficiency (serum creatinineϾ1.5 mg/dl), ARBs have been shownto delay the progression of nephrop-athy. (A)● If one class is not tolerated, the othershould be substituted. (E)● Reduction of protein intake to 0.8–1.0g ⅐ kg body wtϪ1⅐ dayϪ1in individualswith diabetes and the earlier stages ofCKD and to 0.8 g ⅐ kg body wtϪ1⅐dayϪ1in the later stages of CKD mayimprove measures of renal function(urine albumin excretion rate, GFR)and is recommended. (B)● When ACE inhibitors, ARBs, or diuret-ics are used, monitor serum creatinineand potassium levels for the develop-ment of acute kidney disease and hy-perkalemia. (E)● Continued monitoring of urine albu-min excretion to assess both responseto therapy and progression of disease isrecommended. (E)● Consider referral to a physician experi-enced in the care of kidney diseasewhen there is uncertainty about the eti-ology of kidney disease (active urinesediment, absence of retinopathy, rapiddecline in GFR), difficult managementissues, or advanced kidney disease. (B)Diabetic nephropathy occurs in 20–40%of patients with diabetes and is the singleleading cause of end-stage renal disease(ESRD). Persistent albuminuria in therange of 30–299 mg/24 h (microalbu-minuria) has been shown to be the earlieststage of diabetic nephropathy in type 1diabetes and a marker for development ofnephropathy in type 2 diabetes. Mi-croalbuminuria is also a well-establishedmarker of increased CVD risk (226,227).Patients with microalbuminuria whoprogress to macroalbuminuria (300mg/24 h) are likely to progress to ESRD(228,229). However, a number of inter-ventions have been demonstrated to re-duce the risk and slow the progression ofrenal disease.Intensive diabetes management withthe goal of achieving near normoglycemiahas been shown in large prospective ran-domized studies to delay the onset of mi-croalbuminuria and the progression ofmicro- to macroalbuminuria in patientswith type 1 (230,231) and type 2 (49,50)diabetes. The UKPDS provided strong ev-idence that control of blood pressure canreduce the development of nephropathy(163). In addition, large prospective ran-domized studies in patients with type 1diabetes have demonstrated that achieve-ment of lower levels of systolic bloodpressure (Ͻ140 mmHg) resulting fromtreatment using ACE inhibitors provides aselective benefit over other antihyperten-sive drug classes in delaying the progres-sion from micro- to macroalbuminuriaand can slow the decline in GFR inpatients with macroalbuminuria(180,181,232). In type 2 diabetes withhypertension and normoalbuminuria,ACE inhibition has been demonstrated todelay progression to microalbuminuria(233).In addition, ACE inhibitors have beenshown to reduce major CVD outcomes(i.e., myocardial infarction, stroke, death)in patients with diabetes (174), thus fur-ther supporting the use of these agents inpatients with microalbuminuria, a CVDrisk factor. ARBs have also been shown toreduce the rate of progression from mi-cro- to macroalbuminuria as well as ESRDin patients with type 2 diabetes (234–236). Some evidence suggests that ARBshave a smaller magnitude of rise in potas-sium compared with ACE inhibitors inpeople with nephropathy (237,238). It isimportant to note that the benefits of bothACE inhibitors and ARBs in those withdiabetic nephropathy are strongly associ-ated with the reduction in albuminuria.Combinations of drugs that block the ren-nin-angiotensin-aldosterone system (e.g.,an ACE inhibitor plus an ARB, a miner-alocorticoid antagonist, or a direct renininhibitor) have been shown to provide ad-ditional lowering of albuminuria (239–242). However, the long-term effects ofsuch combinations on renal or cardiovas-cular outcomes have not yet been evalu-ated in clinical trials.Other drugs, such as diuretics, cal-cium channel blockers, and ␤-blockers,should be used as additional therapy tofurther lower blood pressure in patientsalready treated with ACE inhibitors orARBs (179) or as alternate therapy in therare individual unable to tolerate ACE in-hibitors or ARBs.Studies in patients with varying stagesof nephropathy have shown that proteinrestriction helps slow the progression ofalbuminuria, GFR decline, and occur-rence of ESRD (243–246). Protein restric-tion should be considered particularly inpatients whose nephropathy seems to beprogressing despite optimal glucose andblood pressure control and use of ACEinhibitor and/or ARBs (246).Assessment of albuminuria statusand renal functionScreening for microalbuminuria can beperformed by measurement of the albu-min-to-creatinine ratio in a random spotcollection (preferred method); 24-h ortimed collections are more burdensomeand add little to prediction or accuracyPosition StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S33
  • 22. (247,248). Measurement of a spot urinefor albumin only, whether by immunoas-say or by using a dipstick test specific formicroalbumin, without simultaneouslymeasuring urine creatinine, is somewhatless expensive but susceptible to false-negative and -positive determinations as aresult of variation in urine concentrationdue to hydration and other factors.Abnormalities of albumin excretionare defined in Table 12. Because of vari-ability in urinary albumin excretion, twoof three specimens collected within a 3- to6-month period should be abnormal be-fore considering a patient to have crossedone of these diagnostic thresholds. Exer-cise within 24 h, infection, fever, CHF,marked hyperglycemia, and marked hy-pertension may elevate urinary albuminexcretion over baseline values.Information on presence of abnormalurine albumin excretion in addition tolevel of GFR may be used to stage CKD.The National Kidney Foundation classifi-cation (Table 13) is primarily based onGFR levels and therefore differs fromother systems, in which staging is basedprimarily on urinary albumin excretion(249). Studies have found decreased GFRin the absence of increased urine albuminexcretion in a substantial percentage ofadults with diabetes (250,251). Epidemi-ologic evidence suggests that a substantialfraction of those with CKD in the settingof diabetes have little or no detectablealbuminuria (250). Serum creatinineshould therefore be measured at least an-nually in all adults with diabetes, regard-less of the degree of urine albuminexcretion.Serum creatinine should be used toestimate GFR and to stage the level ofCKD, if present. GFR can be estimatedusing formulae such as the Cockroft-Gault equation or a prediction formulausing data from the Modification of Dietand Renal Disease study (252). GFRcalculators are available at Many clinical laboratoriesnow report estimated GFR in addition toserum creatinine.The role of continued annual quanti-tative assessment of albumin excretion af-ter diagnosis of microalbuminuria andinstitution of ACE inhibitor or ARB ther-apy and blood pressure control is unclear.Continued surveillance can assess bothresponse to therapy and progression ofdisease. Some suggest that reducing ab-normal albuminuria (Ͼ30 mg/g) to thenormal or near-normal range may im-prove renal and cardiovascular prognosis,but this approach has not been formallyevaluated in prospective trials.Complications of kidney disease cor-relate with level of kidney function. Whenthe estimated GFR is Ͻ60 ml/min per1.73 m2, screening for anemia, malnutri-tion, and metabolic bone disease is indi-cated. Early vaccination against hepatitisB is indicated in patients likely to progressto end-stage kidney disease.Consider referral to a physician ex-perienced in the care of kidney diseasewhen there is uncertainty about the eti-ology of kidney disease (active urinesediment, absence of retinopathy, rapiddecline in GFR), difficult managementissues, or advanced kidney disease. Thethreshold for referral may vary depend-ing on the frequency with which a pro-vider encounters diabetic patients withsignificant kidney disease. Consultationwith a nephrologist when stage 4 CKDdevelops has been found to reduce cost,improve quality of care, and keep peo-ple off dialysis longer (253,254). How-ever, nonrenal specialists should notdelay educating their patients about theprogressive nature of diabetic kidneydisease, the renal preservation benefitsof aggressive treatment of blood pres-sure, blood glucose, and hyperlipid-emia, and the potential need for renalreplacement therapy.C. Retinopathy screening andtreatmentRecommendationsGeneral recommendations● To reduce the risk or slow the progres-sion of retinopathy, optimize glycemiccontrol. (A)● To reduce the risk or slow the progres-sion of retinopathy, optimize bloodpressure control. (A)Screening● Adults and children aged 10 years orolder with type 1 diabetes should havean initial dilated and comprehensiveeye examination by an ophthalmologistor optometrist within 5 years after theonset of diabetes. (B)● Patients with type 2 diabetes shouldhave an initial dilated and comprehen-sive eye examination by an ophthalmol-ogist or optometrist shortly after thediagnosis of diabetes. (B)● Subsequent examinations for type 1and type 2 diabetic patients should berepeated annually by an ophthalmolo-gist or optometrist. Less frequent exams(every 2–3 years) may be consideredfollowing one or more normal eye ex-ams. Examinations will be requiredmore frequently if retinopathy is pro-gressing. (B)● Women with preexisting diabetes whoare planning pregnancy or who havebecome pregnant should have a com-prehensive eye examination and becounseled on the risk of developmentand/or progression of diabetic retinop-athy. Eye examination should occur inthe first trimester with close follow-upthroughout pregnancy and 1 year post-partum. (B)Table 12—Definitions of abnormalities in albumin excretionCategory Spot collection (␮g/mg creatinine)Normal Ͻ30Microalbuminuria 30–299Macro (clinical)-albuminuria Ն300Table 13—Stages of CKDStage DescriptionGFR (ml/min per 1.73 m2body surface area)1 Kidney damage* with normal or increased GFR Ն902 Kidney damage* with mildly decreased GFR 60–893 Moderately decreased GFR 30–594 Severely decreased GFR 15–295 Kidney failure Ͻ15 or dialysis*Kidney damage defined as abnormalities on pathologic, urine, blood, or imaging tests. Adapted andreprinted with permission (248).Standards of Medical CareS34 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 23. Treatment● Promptly refer patients with any level ofmacular edema, severe NPDR, or anyPDR to an ophthalmologist who isknowledgeable and experienced in themanagement and treatment of diabeticretinopathy. (A)● Laser photocoagulation therapy is indi-cated to reduce the risk of vision loss inpatients with high-risk PDR and clini-cally significant macular edema and insome cases of severe NPDR. (A)● The presence of retinopathy is not acontraindication to aspirin therapy forcardioprotection, as this therapy doesnot increase the risk of retinal hemor-rhage. (A)Diabetic retinopathy is a highly specificvascular complication of both type 1 andtype 2 diabetes, with prevalence stronglyrelated to the duration of diabetes. Dia-betic retinopathy is the most frequentcause of new cases of blindness amongadults aged 20–74 years. Glaucoma, cat-aracts, and other disorders of the eye oc-cur earlier and more frequently in peoplewith diabetes.In addition to duration of diabetes,other factors that increase the risk of, orare associated with, retinopathy includechronic hyperglycemia (255), the pres-ence of nephropathy (256), and hyper-tension (257). Intensive diabetesmanagement with the goal of achievingnear normoglycemia has been shown inlarge prospective randomized studies toprevent and/or delay the onset and pro-gression of diabetic retinopathy(45,49,50). Lowering blood pressure hasbeen shown to decrease the progressionof retinopathy (163). Several case seriesand a controlled prospective study sug-gest that pregnancy in type 1 diabetic pa-tients may aggravate retinopathy(258,259); laser photocoagulation sur-gery can minimize this risk (259).One of the main motivations forscreening for diabetic retinopathy is theestablished efficacy of laser photocoagu-lation surgery in preventing vision loss.Two large trials, the Diabetic RetinopathyStudy (DRS) and the Early Treatment Di-abetic Retinopathy Study (ETDRS), pro-vide the strongest support for thetherapeutic benefits of photocoagulationsurgery.The DRS (260) showed that panreti-nal photocoagulation surgery reduced therisk of severe vision loss from PDR from15.9% in untreated eyes to 6.4% intreated eyes. The benefit was greatestamong patients whose baseline evalua-tion revealed high-risk characteristics(chiefly disc neovascularization or vitre-ous hemorrhage). Given the risks of mod-est loss of visual acuity and contraction ofthe visual field from panretinal laser sur-gery, such therapy is primarily recom-mended for eyes with PDR approachingor having high-risk characteristics.The ETDRS (261) established thebenefit of focal laser photocoagulationsurgery in eyes with macular edema, par-ticularly those with clinically significantmacular edema, with reduction of dou-bling of the visual angle (e.g., 20/50 to20/100) from 20% in untreated eyes to8% in treated eyes. The ETDRS also veri-fied the benefits of panretinal photocoag-ulation for high-risk PDR, but not formild or moderate NPDR. In older-onsetpatients with severe NPDR or less-than-high-risk PDR, the risk of severe visionloss or vitrectomy was reduced ϳ50% byearly laser photocoagulation surgery atthese stages.Laser photocoagulation surgery inboth trials was beneficial in reducing therisk of further vision loss, but generallynot beneficial in reversing already dimin-ished acuity. This preventive effect andthe fact that patients with PDR or macularedema may be asymptomatic providestrong support for a screening program todetect diabetic retinopathy.As retinopathy is estimated to take atleast 5 years to develop after the onset ofhyperglycemia (262), patients with type 1diabetes should have an initial dilated andcomprehensive eye examination within 5years after the onset of diabetes. Patientswith type 2 diabetes, who generally havehad years of undiagnosed diabetes (263)and who have a significant risk of preva-lent diabetic retinopathy at time of diabe-tes diagnosis, should have an initialdilated and comprehensive eye examina-tion soon after diagnosis. Examinationsshould be performed by an ophthalmolo-gist or optometrist who is knowledgeableand experienced in diagnosing the pres-ence of diabetic retinopathy and is awareof its management. Subsequent examina-tions for type 1 and type 2 diabetic pa-tients are generally repeated annually.Less frequent exams (every 2–3 years)may be cost effective after one or morenormal eye exams (264–266), while ex-aminations will be required more fre-quently if retinopathy is progressing.Examinations can also be done withretinal photographs (with or without di-lation of the pupil) read by experiencedexperts. In-person exams are still neces-sary when the photos are unacceptableand for follow-up of abnormalities de-tected. This technology has great poten-tial in areas where qualified eye careprofessionals are not available and mayenhance efficiency and reduce costs whenthe expertise of ophthalmologists can beutilized for more complex examinationsand for therapy (267).Results of eye examinations should bedocumented and transmitted to the refer-ring health care professional. For a de-tailed review of the evidence and furtherdiscussion of diabetic retinopathy, see theADA’s technical review and position state-ment on this subject (268,269).D. Neuropathy screening andtreatment (270)Recommendations● All patients should be screened for dis-tal symmetric polyneuropathy (DPN) atdiagnosis and at least annually thereaf-ter using simple clinical tests. (B)● Electrophysiological testing is rarelyneeded, except in situations where theclinical features are atypical. (E)● Screening for signs and symptoms ofcardiovascular autonomic neuropathyshould be instituted at diagnosis of type2 diabetes and 5 years after the diagno-sis of type 1 diabetes. Special testing israrely needed and may not affect man-agement or outcomes. (E)● Medications for the relief of specificsymptoms related to DPN and auto-nomic neuropathy are recommended,as they improve the quality of life of thepatient. (E)The diabetic neuropathies are heteroge-neous with diverse clinical manifesta-tions. They may be focal or diffuse. Mostcommon among the neuropathies arechronic sensorimotor DPN and auto-nomic neuropathy. Although DPN is adiagnosis of exclusion, complex investi-gations to exclude other conditions arerarely needed.The early recognition and appropri-ate management of neuropathy in the pa-tient with diabetes is important for anumber of reasons: 1) nondiabetic neu-ropathies may be present in patients withdiabetes and may be treatable; 2) a num-ber of treatment options exist for symp-tomatic diabetic neuropathy; 3) up to50% of DPN may be asymptomatic, andpatients are at risk of insensate injury totheir feet; 4) autonomic neuropathy mayPosition StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S35
  • 24. involve every system in the body; and 5)cardiovascular autonomic neuropathycauses substantial morbidity and mortal-ity. Specific treatment for the underlyingnerve damage is currently not available,other than improved glycemic control,which may slow progression but not re-verse neuronal loss. Effective symptom-atic treatments are available for somemanifestations of DPN and autonomicneuropathy.Diagnosis of neuropathyDistal symmetric polyneuropathyPatients with diabetes should be screenedannually for DPN using tests such as pin-prick sensation, vibration perception(using a 128-Hz tuning fork), 10-g mono-filament pressure sensation at the distalplantar aspect of both great toes andmetatarsal joints, and assessment of anklereflexes. Combinations of more than onetest have Ͼ87% sensitivity in detectingDPN. Loss of 10-g monofilament percep-tion and reduced vibration perceptionpredict foot ulcers (270).Diabetic autonomic neuropathy (271)The symptoms and signs of autonomicdysfunction should be elicited carefullyduring the history and physical examina-tion. Major clinical manifestations of dia-betic autonomic neuropathy includeresting tachycardia, exercise intolerance,orthostatic hypotension, constipation,gastroparesis, erectile dysfunction, sudo-motor dysfunction, impaired neurovas-cular function, “brittle diabetes,” andhypoglycemic autonomic failure.Cardiovascular autonomic neuropa-thy, a CVD risk factor (93), is the moststudied and clinically important form ofdiabetic autonomic neuropathy. Cardio-vascular autonomic neuropathy may beindicated by resting tachycardia (Ͼ100bpm), orthostasis (a fall in systolic bloodpressure Ͼ20 mmHg upon standingwithout an appropriate heart rate re-sponse), or other disturbances in auto-nomic nervous system function involvingthe skin, pupils, or gastrointestinal andgenitourinary systems.Gastrointestinal neuropathies (e.g.,esophageal enteropathy, gastroparesis,constipation, diarrhea, fecal inconti-nence) are common, and any section ofthe gastrointestinal tract may be affected.Gastroparesis should be suspected in in-dividuals with erratic glucose control orwith upper gastrointestinal symptomswithout other identified cause. Evalua-tion of solid-phase gastric emptying usingdouble-isotope scintigraphy may be doneif symptoms are suggestive, but test re-sults often correlate poorly with symp-toms. Constipation is the most commonlower-gastrointestinal symptom but canalternate with episodes of diarrhea.Diabetic autonomic neuropathy isalso associated with genitourinary tractdisturbances. In men, diabetic autonomicneuropathy may cause erectile dysfunc-tion and/or retrograde ejaculation. Evalu-ation of bladder dysfunction should beperformed for individuals with diabeteswho have recurrent urinary tract infec-tions, pyelonephritis, incontinence, or apalpable bladder.Symptomatic treatmentsDPNThe first step in management of patientswith DPN should be to aim for stable andoptimal glycemic control. Although con-trolled trial evidence is lacking, severalobservational studies suggest that neuro-pathic symptoms improve not only withoptimization of control, but also with theavoidance of extreme blood glucose fluc-tuations. Patients with painful DPN maybenefit from pharmacological treatmentof their symptoms: many agents have ef-ficacy confirmed in published random-ized controlled trials, with several FDA-approved for the management of painfulDPN. See Table 14 for examples of agentsto treat DPN pain.Treatment of autonomic neuropathyGastroparesis symptoms may improvewith dietary changes and prokineticagents such as metoclopramide or eryth-romycin. Treatments for erectile dysfunc-tion may include phosphodiesterase type5 inhibitors, intracorporeal or intraure-thral prostaglandins, vacuum devices, orpenile prostheses. Interventions for othermanifestations of autonomic neuropathyare described in the ADA statement onneuropathy (270). As with DPN treat-ments, these interventions do not changethe underlying pathology and natural his-tory of the disease process but may have apositive impact on the quality of life of thepatient.E. Foot careRecommendations● For all patients with diabetes, performan annual comprehensive foot exami-nation to identify risk factors predictiveof ulcers and amputations. The foot ex-amination should include inspection,assessment of foot pulses, and testingfor loss of protective sensation (10-gmonofilament plus testing any one ofthe following: vibration using 128-Hztuning fork, pinprick sensation, anklereflexes, or vibration perceptionthreshold). (B)● Provide general foot self-care educationto all patients with diabetes. (B)● A multidisciplinary approach is recom-mended for individuals with foot ulcersand high-risk feet, especially those witha history of prior ulcer or amputation.(B)● Refer patients who smoke, have loss ofprotective sensation and structural ab-normalities, or have history of priorlower-extremity complications to footcare specialists for ongoing preventivecare and life-long surveillance. (C)● Initial screening for peripheral arterialdisease (PAD) should include a historyfor claudication and an assessment ofthe pedal pulses. Consider obtaining anTable 14—Table of drugs to treat symptomatic DPNClass Examples Typical doses*Tricyclic drugs Amitriptyline 10–75 mg at bedtimeNortriptyline 25–75 mg at bedtimeImipramine 25–75 mg at bedtimeAnticonvulsants Gabapentin 300–1,200 mg t.i.d.Carbamazepine 200–400 mg t.i.d.Pregabalin† 100 mg t.i.d.5-hydroxytryptamine andnorepinephrine uptakeinhibitorDuloxetine† 60–120 mg dailySubstance P inhibitor Capsaicin cream 0.025–0.075% applied t.i.d. or q.i.d.*Dose response may vary; initial doses should be low and titrated up. †Has FDA indication for treatment ofpainful diabetic neuropathy.Standards of Medical CareS36 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 25. ankle-brachial index (ABI), as many pa-tients with PAD are asymptomatic. (C)● Refer patients with significant claudica-tion or a positive ABI for further vascu-lar assessment and consider exercise,medications, and surgical options. (C)Amputation and foot ulceration, conse-quences of diabetic neuropathy and/orPAD, are common and major causes ofmorbidity and disability in people withdiabetes. Early recognition and manage-ment of risk factors can prevent or delayadverse outcomes.The risk of ulcers or amputations isincreased in people who have the follow-ing risk factors:● previous amputation● past foot ulcer history● peripheral neuropathy● foot deformity● peripheral vascular disease● vision impairment● diabetic nephropathy (especially pa-tients on dialysis)● poor glycemic control● cigarette smokingMany studies have been published pro-posing a range of tests that might usefullyidentify patients at risk of foot ulceration,creating confusion among practitioners asto which screening tests should beadopted in clinical practice. An ADA taskforce was therefore assembled in 2008 toconcisely summarize recent literature inthis area and then recommend whatshould be included in the comprehensivefoot exam for adult patients with diabetes.Their recommendations are summarizedbelow, but clinicians should refer to thetask force report (272) for further detailsand practical descriptions of how to per-form components of the comprehensivefoot examination.At least annually, all adults with dia-betes should undergo a comprehensivefoot examination to identify high-riskconditions. Clinicians should ask abouthistory of previous foot ulceration or am-putation, neuropathic or peripheral vas-cular symptoms, impaired vision, tobaccouse, and foot care practices. A general in-spection of skin integrity and musculo-skeletal deformities should be done in awell-lit room. Vascular assessment shouldinclude inspection and assessment ofpedal pulses.The neurologic exam recommendedis designed to identify loss of protectivesensation (LOPS) rather than early neu-ropathy. The clinical examination to iden-tify LOPS is simple and requires noexpensive equipment. Five simple clinicaltests (use of a 10-g monofilament, vibra-tion testing using a 128-Hz tuning fork,tests of pinprick sensation, ankle reflexassessment, and testing vibration percep-tion threshold with a biothesiometer),each with evidence from well-conductedprospective clinical cohort studies, areconsidered useful in the diagnosis ofLOPS in the diabetic foot. The task forceagrees that any of the five tests listed couldbe used by clinicians to identify LOPS,although ideally two of these should beregularly performed during the screeningexam—normally the 10-g monofilamentand one other test. One or more abnormaltests would suggest LOPS, while at leasttwo normal tests (and no abnormal test)would rule out LOPS. The last test listed,vibration assessment using a biothesiom-eter or similar instrument, is widely usedin the U.S.; however, identification of thepatient with LOPS can easily be carriedout without this or other expensiveequipment.Initial screening for PAD should in-clude a history for claudication and anassessment of the pedal pulses. A diagnos-tic ABI should be performed in any pa-tient with symptoms of PAD. Due to thehigh estimated prevalence of PAD in pa-tients with diabetes and the fact that manypatients with PAD are asymptomatic, anADA consensus statement on PAD (273)suggested that a screening ABI be per-formed in patients over 50 years of ageand be considered in patients under 50years of age who have other PAD risk fac-tors (e.g., smoking, hypertension, hyper-lipidemia, or duration of diabetes Ͼ10years). Refer patients with significantsymptoms or a positive ABI for furthervascular assessment and consider exer-cise, medications, and surgical options(273).Patients with diabetes and high-riskfoot conditions should be educated re-garding their risk factors and appropriatemanagement. Patients at risk should un-derstand the implications of the loss ofprotective sensation, the importance offoot monitoring on a daily basis, theproper care of the foot, including nail andskin care, and the selection of appropriatefootwear. Patients with loss of protectivesensation should be educated on ways tosubstitute other sensory modalities (handpalpation, visual inspection) for surveil-lance of early foot problems. The patient’sunderstanding of these issues and theirphysical ability to conduct proper footsurveillance and care should be assessed.Patients with visual difficulties, physicalconstraints preventing movement, or cog-nitive problems that impair their ability toassess the condition of the foot and to in-stitute appropriate responses will needother people, such as family members, toassist in their care.People with neuropathy or evidenceof increased plantar pressure (e.g., ery-thema, warmth, callus, or measuredpressure) may be adequately managedwith well-fitted walking shoes or ath-letic shoes that cushion the feet and re-distribute pressure. Callus can bedebrided with a scalpel by a foot carespecialist or other health professionalwith experience and training in footcare. People with bony deformities(e.g., hammertoes, prominent metatar-sal heads, bunions) may need extra-wide or -depth shoes. People withextreme bony deformities (e.g., Charcotfoot) who cannot be accommodatedwith commercial therapeutic footwearmay need custom-molded shoes.Foot ulcers and wound care may re-quire care by a podiatrist, orthopedic orvascular surgeon, or rehabilitation spe-cialist experienced in the managementof individuals with diabetes. For a com-plete discussion, see the ADA’s consen-sus statement on diabetic foot woundcare (274).VII. DIABETES CARE INSPECIFIC POPULATIONSA. Children and adolescents1. Type 1 diabetesThree-quarters of all cases of type 1 dia-betes are diagnosed in individuals Ͻ18years of age. Because children are not sim-ply “small adults,” it is appropriate to con-sider the unique aspects of care andmanagement of children and adolescentswith type 1 diabetes. Children with dia-betes differ from adults in many respects,including changes in insulin sensitivityrelated to sexual maturity and physicalgrowth, ability to provide self-care, super-vision in child care and school, andunique neurologic vulnerability to hypo-glycemia and DKA. Attention to such is-sues as family dynamics, developmentalstages, and physiologic differences relatedto sexual maturity are all essential in de-veloping and implementing an optimaldiabetes regimen. Although recommen-dations for children and adolescents arePosition StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S37
  • 26. less likely to be based on clinical trial ev-idence, because of current and historicalrestraints placed on conducting researchin children, expert opinion and a reviewof available and relevant experimentaldata are summarized in the ADA state-ment on care of children and adolescentswith type 1 diabetes (275).Ideally, the care of a child or adoles-cent with type 1 diabetes should be pro-vided by a multidisciplinary team ofspecialists trained in the care of childrenwith pediatric diabetes. At the very least,education of the child and family shouldbe provided by health care providerstrained and experienced in childhood di-abetes and sensitive to the challengesposed by diabetes in this age-group. Atthe time of initial diagnosis, it is essentialthat diabetes education be provided in atimely fashion, with the expectation thatthe balance between adult supervisionand self-care should be defined by, andwill evolve according to, physical, psy-chological, and emotional maturity. MNTshould be provided at diagnosis, and atleast annually thereafter, by an individualexperienced with the nutritional needs ofthe growing child and the behavioral is-sues that have an impact on adolescentdiets, including risk for disordered eating.a. Glycemic controlRecommendations● Consider age when setting glycemicgoals in children and adolescents withtype 1 diabetes, with less stringent goalsfor younger children. (E)While current standards for diabetesmanagement reflect the need to maintainglucose control as near to normal as safelypossible, special consideration must begiven to the unique risks of hypoglycemiain young children. Glycemic goals need tobe modified to take into account the factthat most children Ͻ6 or 7 years of agehave a form of hypoglycemic unaware-ness. Their counterregulatory mecha-nisms are immature and they may lack thecognitive capacity to recognize and re-spond to hypoglycemic symptoms, plac-ing them at greater risk for severehypoglycemia and its sequelae. In addi-tion, and unlike the case in adults, youngchildren below the age of 5 years are atrisk for permanent cognitive impairmentafter episodes of severe hypoglycemia(276–278). Extensive evidence indicatesthat near normalization of blood glucoselevels is seldom attainable in children andadolescents after the honeymoon (remis-sion) period. The A1C level achieved inthe “intensive” adolescent cohort of theDCCT group was Ͼ1% higher than thatachieved by adult DCCT subjects andabove current ADA recommendations forpatients in general. However, the in-creased frequency of use of basal bolusregimens (including insulin pumps) inyouth from infancy through adolescencehas been associated with more childrenreaching ADA blood glucose targets(279,280) in those families in which bothparents and the child with diabetes aremotivated to perform the required diabe-tes-related tasks.In selecting glycemic goals, the bene-fits on long-term health outcomes ofachieving a lower A1C must be weighedagainst the unique risks of hypoglycemiaand the difficulties achieving near normo-glycemia in children and youth. Age-specific glycemic and A1C goals arepresented in Table 15.b. Screening and management ofchronic complications in children andadolescents with type 1 diabetesi. NephropathyRecommendations● Annual screening for microalbumin-uria, with a random spot urine samplefor microalbumin-to-creatinine ratio,should be initiated once the child is 10years of age and has had diabetes for 5years. (E)● Confirmed, persistently elevated mi-croalbumin levels on two additionalurine specimens should be treated withan ACE inhibitor, titrated to normaliza-tion of microalbumin excretion if pos-sible. (E)ii. HypertensionRecommendations● Treatment of high-normal blood pres-sure (systolic or diastolic blood pres-sure consistently between the 90–95thpercentile for age, sex, and height)should include dietary interventionand exercise aimed at weight controland increased physical activity, if ap-propriate. If target blood pressure is notTable 15—Plasma blood glucose and A1C goals for type 1 diabetes by age-groupValues by age (years)Plasma blood glucose goal range(mg/dl)A 1C RationaleBefore meals Bedtime/overnightToddlers and preschoolers (0–6) 100–180 110–200 Ͻ8.5% (but Ͼ7.5%) High risk and vulnerability tohypoglycemiaSchool age (6–12) 90–180 100–180 Ͻ8% Risks of hypoglycemia and relativelylow risk of complications prior topubertyAdolescents and young adults (13–19) 90–130 90–150 Ͻ7.5% ● Risk of severe hypoglycemia● Developmental and psychologicalissues● A lower goal (Ͻ7.0%) isreasonable if it can be achievedwithout excessive hypoglycemiaKey concepts in setting glycemic goals:● Goals should be individualized and lower goals may be reasonable based on benefit-risk assessment.● Blood glucose goals should be higher than those listed above in children with frequent hypoglycemia or hypoglycemia unawareness.● Postprandial blood glucose values should be measured when there is a discrepancy between pre-prandial blood glucose values and A1Clevels and to help assess glycemia in those on basal/bolus regimens.Standards of Medical CareS38 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 27. reached with 6–12 months of lifestyleintervention, pharmacologic treatmentshould be initiated. (E)● Pharmacologic treatment of high bloodpressure (systolic or diastolic bloodpressure consistently above the 95thpercentile for age, sex, and height orconsistently Ͼ130/80 mmHg for ado-lescents) should be initiated along withlifestyle intervention as soon as the di-agnosis is confirmed. (E)● ACE inhibitors should be consideredfor the initial treatment of hyperten-sion. (E)● The goal of treatment is a blood pres-sure consistently Ͻ130/80 or below the90th percentile for age, sex, and height,whichever is lower. (E)Hypertension in childhood is defined asan average systolic or diastolic blood pres-sure 95th percentile for age, sex, andheight percentile measured on at least 3separate days. “High-normal” blood pres-sure is defined as an average systolic ordiastolic blood pressure 90th but Ͻ95thpercentile for age, sex, and height percen-tile measured on at least 3 separate days.Normal blood pressure levels for age, sex,and height and appropriate methods fordeterminations are available online DyslipidemiaRecommendationsScreening● If there is a family history of hypercho-lesterolemia (total cholesterol Ͼ240mg/dl) or a cardiovascular event beforeage 55 years, or if family history is un-known, then a fasting lipid profileshould be performed on children Ͼ2years of age soon after diagnosis (afterglucose control has been established).If family history is not of concern, thenthe first lipid screening should be per-formed at puberty (Ն10 years). All chil-dren diagnosed with diabetes at or afterpuberty should have a fasting lipid pro-file performed soon after diagnosis(after glucose control has been estab-lished). (E)● For both age-groups, if lipids are abnor-mal, annual monitoring is recom-mended. If LDL cholesterol values arewithin the accepted risk levels (Ͻ100mg/dl [2.6 mmol/l]), a lipid profileshould be repeated every 5 years. (E)Treatment● Initial therapy should consist of optimi-zation of glucose control and MNT us-ing a Step 2 AHA diet aimed at adecrease in the amount of saturated fatin the diet. (E)● After the age of 10, the addition of astatin is recommended in patients who,after MNT and lifestyle changes, haveLDL Ͼ160 mg/dl (4.1 mmol/l) or LDLcholesterol Ͼ130 mg/dl (3.4 mmol/l)and one or more CVD risk factors. (E)● The goal of therapy is an LDL choles-terol value Ͻ100 mg/dl (2.6 mmol/l).(E)People diagnosed with type 1 diabetes inchildhood have a high risk of early sub-clinical (281–283) and clinical (284)CVD. Although intervention data arelacking, the AHA categorizes type 1 chil-dren in the highest tier for cardiovascularrisk and recommends both lifestyle andpharmacologic treatment for those withelevated LDL cholesterol levels(285,286). Initial therapy should be witha Step 2 AHA diet, which restricts satu-rated fat to 7% of total calories and re-stricts dietary cholesterol to 200 mg perday. Data from randomized clinical trialsin children as young as 7 months of ageindicate that this diet is safe and does notinterfere with normal growth and devel-opment (287,288).For children over the age of 10 withpersistent elevation of LDL cholesteroldespite lifestyle therapy, statins should beconsidered. Neither long-term safety norcardiovascular outcome efficacy has beenestablished for children. However, recentstudies have shown short-term safetyequivalent to that seen in adults and effi-cacy in lowering LDL cholesterol levels,improving endothelial function, andcausing regression of carotid intimalthickening (289–291). No statin is ap-proved for use under the age of 10, andstatin treatment should generally not beused in type 1 children before this age.iv. RetinopathyRecommendations● The first ophthalmologic examinationshould be obtained once the child isՆ10 years of age and has had diabetesfor 3–5 years. (E)● After the initial examination, annualroutine follow-up is generally recom-mended. Less frequent examinationsmay be acceptable on the advice of aneye care professional. (E)Although retinopathy most commonlyoccurs after the onset of puberty and after5–10 years of diabetes duration, it hasbeen reported in prepubertal childrenand with diabetes duration of only 1–2years. Referrals should be made to eyecare professionals with expertise in dia-betic retinopathy, an understanding ofthe risk for retinopathy in the pediatricpopulation, and experience in counselingthe pediatric patient and family on theimportance of early prevention/intervention.v. Celiac diseaseRecommendations● Patients with type 1 diabetes should bescreened for celiac disease by measur-ing tissue transglutaminase or anti-endomysial antibodies, withdocumentation of normal serum IgAlevels, soon after the diagnosis of diabe-tes. (E)● Testing should be repeated if growthfailure, failure to gain weight, weightloss, or gastroenterologic symptoms oc-cur. (E)● Consideration should be given to peri-odic re-screening of asymptomatic in-dividuals. (E)● Children with positive antibodiesshould be referred to a gastroenterolo-gist for evaluation. (E)● Children with confirmed celiac diseaseshould have consultation with a dietitianand placed on a gluten-free diet. (E)Celiac disease is an immune-mediateddisorder that occurs with increased fre-quency in patients with type 1 diabetes(1–16% of individuals compared with0.3–1% in the general population)(292,293). Symptoms of celiac disease in-clude diarrhea, weight loss or poor weightgain, growth failure, abdominal pain,chronic fatigue, malnutrition due to mal-absorption, and other gastrointestinalproblems and unexplained hypoglycemiaor erratic blood glucose HypothyroidismRecommendations● Patients with type 1 diabetes should bescreened for thyroid peroxidase andthyroglobulin antibodies at diagnosis.(E)● TSH concentrations should be mea-sured after metabolic control has beenestablished. If normal, they should berechecked every 1–2 years, or if the pa-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S39
  • 28. tient develops symptoms of thyroiddysfunction, thyromegaly, or an abnor-mal growth rate. Free T4 should bemeasured if TSH is abnormal. (E)Autoimmune thyroid disease is the mostcommon autoimmune disorder associ-ated with diabetes, occurring in 17–30%of patients with type 1 diabetes (294). Thepresence of thyroid autoantibodies is pre-dictive of thyroid dysfunction, generallyhypothyroidism but less commonly hy-perthyroidism (295). Subclinical hypo-thyroidism may be associated withincreased risk of symptomatic hypoglyce-mia (296) and with reduced linear growth(297). Hyperthyroidism alters glucosemetabolism, potentially resulting in dete-rioration of metabolic control.c. “Adherence.” No matter how soundthe medical regimen, it can only be asgood as the ability of the family and/orindividual to implement it. Family in-volvement in diabetes remains an impor-tant component of optimal diabetesmanagement throughout childhood andinto adolescence. Health care providerswho care for children and adolescents,therefore, must be capable of evaluatingthe behavioral, emotional, and psychoso-cial factors that interfere with implemen-tation and then must work with theindividual and family to resolve problemsthat occur and/or to modify goals as ap-propriate.d. School and day care. Since a sizableportion of a child’s day is spent in school,close communication with school or daycare personnel is essential for optimal di-abetes management, safety, and maximalacademic opportunities. See SectionV.III.B, Diabetes Care in the School andDay Care Setting, for further discussion.2. Type 2 diabetesThe incidence of type 2 diabetes in ado-lescents is increasing, especially in ethnicminority populations (20). Distinctionbetween type 1 and type 2 diabetes inchildren can be difficult, since the preva-lence of overweight in children continuesto rise and since autoantigens and ketosismay be present in a substantial number ofpatients with features of type 2 diabetes(including obesity and acanthosis nigri-cans). Such a distinction at the time ofdiagnosis is critical because treatmentregimens, educational approaches, anddietary counsel will differ markedly be-tween the two diagnoses. Because type 2diabetes has a significant incidence ofhypertension, dyslipidemia, and mi-croalbuminuria at diagnosis (298), it isrecommended that screening for the co-morbidities and complications of diabe-tes, including fasting lipid profile,microalbuminuria assessment, and di-lated eye examinations, begin at the timeof diagnosis. The ADA consensus state-ment on this subject (22) provides guid-ance on the prevention, screening, andtreatment of type 2 diabetes and its co-morbidities in young people.B. Preconception careRecommendations● A1Clevelsshouldbeasclosetonormalaspossible (Ͻ7%) in an individual patientbefore conception is attempted. (B)● Starting at puberty, preconceptioncounseling should be incorporated inthe routine diabetes clinic visit for allwomen of child-bearing potential. (C)● Women with diabetes who are contem-plating pregnancy should be evaluatedand, if indicated, treated for diabeticretinopathy, nephropathy, neuropathy,and CVD. (E)● Medications used by such womenshould be evaluated before conception,since drugs commonly used to treat di-abetes and its complications may becontraindicated or not recommendedin pregnancy, including statins, ACEinhibitors, ARBs, and most noninsulintherapies. (E)Major congenital malformations remainthe leading cause of mortality and seriousmorbidity in infants of mothers with type1 and type 2 diabetes. Observational stud-ies indicate that the risk of malformationsincreases continuously with increasingmaternal glycemia during the first 6–8weeks of gestation, as defined by first-trimester A1C concentrations. There is nothreshold for A1C values below whichrisk disappears entirely. However, mal-formation rates above the 1–2% back-ground rate of nondiabetic pregnanciesappear to be limited to pregnancies inwhich first-trimester A1C concentrationsare Ͼ1% above the normal range for anondiabetic pregnant woman.Preconception care of diabetes ap-pears to reduce the risk of congenital mal-formations. Five nonrandomized studiescompared rates of major malformations ininfants between women who participatedin preconception diabetes care programsand women who initiated intensive diabe-tes management after they were alreadypregnant. The preconception care pro-grams were multidisciplinary and de-signed to train patients in diabetes self-management with diet, intensified insulintherapy, and SMBG. Goals were set toachieve normal blood glucose concentra-tions, and Ͼ80% of subjects achievednormal A1C concentrations before theybecame pregnant (299–303). In all fivestudies, the incidence of major congenitalmalformations in women who partici-pated in preconception care (range 1.0–1.7% of infants) was much lower than theincidence in women who did not partici-pate (range 1.4–10.9% of infants). Onelimitation of these studies is that partici-pation in preconception care was self-selected rather than randomized. Thus, itis impossible to be certain that the lowermalformation rates resulted fully fromimproved diabetes care. Nonetheless, theevidence supports the concept that mal-formations can be reduced or preventedby careful management of diabetes beforepregnancy.Planned pregnancies greatly facilitatepreconception diabetes care. Unfortu-nately, nearly two-thirds of pregnanciesin women with diabetes are unplanned,leading to a persistent excess of malfor-mations in infants of diabetic mothers. Tominimize the occurrence of these devas-tating malformations, standard care for allwomen with diabetes who have child-bearing potential, beginning at the onsetof puberty or at diagnosis, should include1) education about the risk of malforma-tions associated with unplanned pregnan-cies and poor metabolic control and 2)use of effective contraception at all times,unless the patient has good metaboliccontrol and is actively trying to conceive.Women contemplating pregnancyneed to be seen frequently by a multidis-ciplinary team experienced in the man-agement of diabetes before and duringpregnancy. The goals of preconceptioncare are to 1) involve and empower thepatient in the management of her diabe-tes, 2) achieve the lowest A1C test resultspossible without excessive hypoglycemia,3) assure effective contraception until sta-ble and acceptable glycemia is achieved,and 4) identify, evaluate, and treat long-term diabetic complications such as reti-nopathy, nephropathy, neuropathy,hypertension, and CHD.Among the drugs commonly used inthe treatment of patients with diabetes, anumber may be relatively or absolutelycontraindicated during pregnancy. St-atins are category X (contraindicated foruse in pregnancy) and should be discon-Standards of Medical CareS40 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 29. tinued before conception, as should ACEinhibitors (304). ARBs are category C(risk cannot be ruled out) in the first tri-mester but category D (positive evidenceof risk) in later pregnancy and shouldgenerally be discontinued before preg-nancy. Among the oral antidiabeticagents, metformin and acarbose are clas-sified as category B (no evidence of risk inhumans) and all others as category C. Po-tential risks and benefits of oral antidia-betic agents in the preconception periodmust be carefully weighed, recognizingthat data are insufficient to establish thesafety of these agents in pregnancy.For further discussion of preconcep-tion care, see the ADA’s technical review(305) and position statement (306) onthis subject.C. Older adultsRecommendations● Older adults who are functional, cogni-tively intact, and have significant lifeexpectancy should receive diabetestreatment using goals developed foryounger adults. (E)● Glycemic goals for older adults not meet-ing the above criteria may be relaxed us-ingindividualcriteria,buthyperglycemialeading to symptoms or risk of acute hy-perglycemic complications should beavoided in all patients. (E)● Other cardiovascular risk factorsshould be treated in older adults withconsideration of the time frame of ben-efit and the individual patient. Treat-ment of hypertension is indicated invirtually all older adults, and lipid andaspirin therapy may benefit those withlife expectancy at least equal to the timeframe of primary or secondary preven-tion trials. (E)● Screening for diabetes complicationsshould be individualized in olderadults, but particular attention shouldbe paid to complications that wouldlead to functional impairment. (E)Diabetes is an important health conditionfor the aging population; at least 20% ofpatients over the age of 65 years have di-abetes, and this number can be expectedto grow rapidly in the coming decades.Older individuals with diabetes havehigher rates of premature death, func-tional disability, and coexisting illnessessuch as hypertension, CHD, and strokethan those without diabetes. Older adultswith diabetes are also at greater risk thanother older adults for several common ge-riatric syndromes, such as polypharmacy,depression, cognitive impairment, uri-nary incontinence, injurious falls, andpersistent pain.The American Geriatric Society’sguidelines for improving the care of theolder person with diabetes (307) have in-fluenced the following discussion andrecommendations. The care of olderadults with diabetes is complicated bytheir clinical and functional heterogene-ity. Some older individuals developed di-abetes years earlier and may havesignificant complications; others who arenewly diagnosed may have had years ofundiagnosed diabetes with resultant com-plications or may have few complicationsfrom the disease. Some older adults withdiabetes are frail and have other underly-ing chronic conditions, substantial diabe-tes-related comorbidity, or limitedphysical or cognitive functioning. Otherolder individuals with diabetes have littlecomorbidity and are active. Life expectan-cies are highly variable for this popula-tion, but often longer than cliniciansrealize. Providers caring for older adultswith diabetes must take this heterogeneityinto consideration when setting and pri-oritizing treatment goals.There are few long-term studies inolder adults demonstrating the benefits ofintensive glycemic, blood pressure, andlipid control. Patients who can be ex-pected to live long enough to reap thebenefits of long-term intensive diabetesmanagement and who are active, havegood cognitive function, and are willingto undertake the responsibility of self-management should be encouraged to doso and be treated using the goals foryounger adults with diabetes.For patients with advanced diabetescomplications, life-limiting comorbid ill-ness, or substantial cognitive or func-tional impairment, it is reasonable to setless intensive glycemic target goals. Thesepatients are less likely to benefit from re-ducing the risk of microvascular compli-cations and more likely to suffer seriousadverse effects from hypoglycemia. How-ever, patients with poorly controlled dia-betes may be subject to acutecomplications of diabetes, including de-hydration, poor wound healing, and hy-perglycemic hyperosmolar coma.Glycemic goals at a minimum shouldavoid these consequences.Although control of hyperglycemiamay be important in older individuals withdiabetes, greater reductions in morbidityand mortality may result from control ofother cardiovascular risk factors rather thanfrom tight glycemic control alone. There isstrong evidence from clinical trials of thevalue of treating hypertension in the elderly(308,309). There is less evidence for lipid-lowering and aspirin therapy, although thebenefits of these interventions for primaryand secondary prevention are likely to ap-ply to older adults whose life expectanciesequalorexceedthetimeframesseeninclin-ical trials.Special care is required in prescribingand monitoring pharmacologic therapy inolder adults. Metformin is often contrain-dicated because of renal insufficiency orsignificant heart failure. TZDs can causefluid retention, which may exacerbate orlead to heart failure. They are contraindi-cated in patients with CHF (New YorkHeart Association class III and IV) and ifused at all should be used very cautiouslyin those with, or at risk for, milder degreesof CHF. Sulfonylureas, other insulinsecretagogues, and insulin can cause hy-poglycemia. Insulin use requires that pa-tients or caregivers have good visual andmotor skills and cognitive ability. Drugsshould be started at the lowest dose andtitrated up gradually until targets arereached or side effects develop.Screening for diabetes complications inolder adults also should be individualized.Particular attention should be paid to com-plications that can develop over short peri-ods of time and/or that would significantlyimpair functional status, such as visual andlower-extremity complications.VIII. DIABETES CARE INSPECIFIC SETTINGSA. Diabetes care in the hospitalRecommendations● All patients with diabetes admitted to thehospital should have their diabetesclearly identified in the medical record.(E)● All patients with diabetes should havean order for blood glucose monitoring,with results available to all members ofthe health care team. (E)● Goals for blood glucose levels:● Critically ill surgical patients’ bloodglucose levels should be kept as closeto 110 mg/dl (6.1 mmol/l) as possibleand generally Ͻ140 mg/dl (7.8mmol/l). (A) These patients requirean intravenous insulin protocol thathas demonstrated efficacy and safetyin achieving the desired glucosePosition StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S41
  • 30. range without increasing risk for se-vere hypoglycemia. (E)● Critically ill nonsurgical patients’ gly-cemic targets are less well defined. In-travenous insulin infusion protocolstargeting blood glucose levelsϽ110–140 mg/dl have been shownto reduced morbidity and mortalityin some, but not all studies. Intrave-nous insulin infusion protocols thateffectively and safely keep blood glu-cose Ͻ140 mg/dl are recommended.(C)● For non–critically ill patients, thereis no clear evidence for specific bloodglucose goals. Since cohort data sug-gest that outcomes are better in hos-pitalized patients with fasting glucoseϽ126 mg/dl and all random glucosesϽ180–200, these goals are reason-able if they can be safely achieved.Insulin is the preferred drug to treathyperglycemia in most cases. (E)● Due to concerns regarding the risk ofhypoglycemia, some institutions mayconsider these blood glucose levels tobe overly aggressive for initial targets.Through quality improvement, glyce-mic goals should systematically be re-duced to the recommended levels. (E)● Scheduled prandial insulin dosesshould be appropriately timed in rela-tion to meals and should be adjustedaccording to point-of-care glucose lev-els. The traditional sliding-scale insulinregimens are ineffective as mono-therapy and are generally not recom-mended. (C)● Using correction dose or “supplemen-tal” insulin to correct premeal hyper-glycemia in addition to scheduledprandial and basal insulin is recom-mended. (E)● Glucose monitoring with orders forcorrection insulin should be initiated inany patient not known to be diabeticwho receives therapy associated withhigh risk for hyperglycemia, includinghigh-dose glucocorticoids therapy, ini-tiation of enteral or parenteral nutri-tion, or other medications such asoctreotide or immunosuppressivemedications. (B) If hyperglycemia isdocumented and persistent, initiationof basal/bolus insulin therapy may benecessary. Such patients should betreated to the same glycemic goals aspatients with known diabetes. (E)● A plan for treating hypoglycemiashould be established for each patient.Episodes of hypoglycemia in the hospi-tal should be tracked. (E)● All patients with diabetes admitted tothe hospital should have an A1C ob-tained if the result of testing in the pre-vious 2–3 months is not available. (E)● A diabetes education plan including“survival skills education” and fol-low-up should be developed for eachpatient. (E)● Patients with hyperglycemia in the hos-pital who do not have a diagnosis ofdiabetes should have appropriate plansfor follow-up testing and care docu-mented at discharge. (E)The management of diabetes in the hos-pital is extensively reviewed in an ADAtechnical review (310). This review, aswell as a consensus statement by theAmerican Association of Clinical Endocri-nologists (AACE) with co-sponsorship byADA (311,312) and a report of a jointADA-AACE task force on the topic (313),form the basis for the discussion andguidelines in this section.The literature on hospitalized pa-tients with hyperglycemia typically de-scribes three categories:● Medical history of diabetes: diabetespreviously diagnosed and acknowl-edged by the patient’s treating physi-cian.● Unrecognized diabetes: hyperglycemia(fasting blood glucose 126 mg/dl orrandom blood glucose 200 mg/dl) oc-curring during hospitalization and con-firmed as diabetes after hospitalizationby standard diagnostic criteria but un-recognized as diabetes by the treatingphysician during hospitalization.● Hospital-related hyperglycemia: hyper-glycemia (fasting blood glucose 126mg/dl or random blood glucose Ն200mg/dl) occurring during the hospital-ization that reverts to normal after hos-pital discharge.The prevalence of diabetes in hospitalizedadult patients is not precisely known. Inthe year 2000, 12.4% of hospital dis-charges in the U.S. listed diabetes as adiagnosis, but this is likely an underesti-mate. The prevalence of diabetes in hos-pitalized adults is conservativelyestimated at 12–25%, depending on thethoroughness used in identifying pa-tients. In the year 2003, there were 5.1million hospitalizations with diabetes as alisted diagnosis, a 2.3-fold increase over1980 rates (314).The management of hyperglycemia inthe hospital was traditionally consideredsecondary in importance to the conditionthat prompted admission (313).A rapidly growing body of literaturesupports targeted glucose control in thehospital setting for potential improvedmortality, morbidity, and health eco-nomic outcomes. Hyperglycemia in thehospital may result from stress, decom-pensation of type 1 or type 2 or otherforms of diabetes, and/or may be iatro-genic due to withholding of antihypergly-cemic medications or administration ofhyperglycemia-provoking agents such asglucocorticoids or vasopressors.1. In-hospital hyperglycemia andoutcomesa. General medicine and surgery. Ob-servational studies suggest an associationbetween hyperglycemia and increasedmortality. Surgical patients with at leastone blood glucose value Ͼ220 mg/dl(12.2 mmol/l) on the first postoperativeday have significantly higher infectionrates (315).When admissions on general medi-cine and surgery units were studied, pa-tients with new hyperglycemia hadsignificantly increased in-hospital mortal-ity, as did patients with known diabetes.In addition, length of stay was higher forthe new hyperglycemic group, and pa-tients in either hyperglycemic group weremore likely to require intensive care unit(ICU) care and transitional or nursinghome care. Better outcomes were demon-strated in patients with fasting and admis-sion blood glucose Ͻ126 mg/dl (7mmol/l) and all random blood glucoselevels Ͻ200 mg/dl (11.1 mmol/l) (316).b. CVD and critical care. A significantrelationship exists between blood glucoselevels and mortality in the setting of acutemyocardial infarction. A meta-analysis of15 studies compared in-hospital mortal-ity in both hyper- and normoglycemic pa-tients with and without diabetes. Insubjects without known diabetes whoseadmission blood glucose averaged 109.8mg/dl (6.1 mmol/l), the relative risk forin-hospital mortality was increased signif-icantly. When diabetes was present andadmission glucose averaged 180 mg/dl(10 mmol/l), risk of death was moderatelyincreased compared with patients whohad diabetes but less hyperglycemia onadmission (317). Another study (318)demonstrated a strong independent rela-tionship between admission blood glu-cose values and both in-hospital and1-year mortality; rates were significantlylower in subjects with admission plasmaStandards of Medical CareS42 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 31. glucose Ͻ100.8 mg/dl (5.6 mmol/l) thanin those with plasma glucose 199.8 mg/dl(11 mmol/l).These studies focused on admissionblood glucose as a predictor of outcomes,rather than inpatient glycemic manage-ment per se. Higher admission plasmaglucose levels in patients with a prior his-tory of diabetes could reflect the degree ofglycemic control in the outpatient setting,thus linking outpatient glycemic controlto outcomes in the inpatient population.In patients without a prior history of dia-betes, admission hyperglycemia couldrepresent case finding of patients withpreviously undiagnosed diabetes, an un-masking of risk in a population at highrisk for diabetes or more severe illness atadmission.In the initial Diabetes and Insulin-Glucose Infusion in Acute Myocardial In-farction (DIGAMI) study (319,320),insulin-glucose infusion followed by atleast 3 months of subcutaneous insulintreatment in diabetic patients with acutemyocardial infarction improved long-term survival. Mean blood glucose in theintensive insulin intervention arm was172.8 mg/dl (9.6 mmol/l), compared with210.6 mg/dl (11.7 mmol/l) in the “con-ventional” group. The broad range ofblood glucose levels within each arm lim-its the ability to define specific blood glu-cose target thresholds.Three more recent studies (321–323)using an insulin-glucose infusion did notshow a reduction in mortality in the inter-vention groups. However, in each of thesestudies, blood glucose levels were posi-tively correlated with mortality. In theHyperglycemia: Intensive Insulin Infu-sion In Infarction (HI-5) study, a decreasein both CHF and reinfarction was ob-served in the group receiving intensive in-sulin therapy for at least 24 h.c. Cardiac surgery. Attainment of tar-geted glucose control in patients with di-abetes undergoing cardiac surgery isassociated with reduced mortality andrisk of deep sternal wound infections(324,325). Although these studies usedhistorical controls and were not random-ized, they support the concept that peri-operative hyperglycemia is anindependent predictor of infection in pa-tients with diabetes (326), with the lowestmortality in patients with blood glucoseϽ150 mg/dl (8.3 mmol/l) (327).d. Critical care. A mixed group of patientswith and without diabetes admitted to asurgical ICU were randomized to receiveintensive insulin therapy (target bloodglucose 80–110 mg/dl [4.4–6.1 mmol/l])or conventional therapy. Intensive insulintherapy achieved a mean blood glucose of103 mg/dl (5.7 mmol/l) and was associ-ated with reduced mortality during theICU stay and decreased overall in-hospital mortality (328). Hospital andICU survival were linearly associated withICU glucose levels, with the highest sur-vival rates occurring in patients achievingan average blood glucose Ͻ110 mg/dl(6.1 mmol/l) (329).A subsequent study of a similar inter-vention in patients in a medical ICU (330)showed that the group receiving intensiveinsulin therapy had reduced morbiditybut no difference in mortality overall.Death rates were significantly lower inthose patients who were treated for longerthan 3 days; but these patients could notbe identified before therapy. In anotherstudy using a similar intervention target-ing a blood glucose range of 4.4–6.1mmol in patients admitted with sepsis, nodifference in mortality from the conven-tionally treated group was observed.There were more episodes of hypoglyce-mia, defined as a blood glucose Ͻ40mg/dl (2.2 mmol/l), and more serious ad-verse events in the group receiving inten-sive insulin therapy (331).While an earlier meta-analysis con-cluded that insulin therapy in critically illpatients had a beneficial effect on short-term mortality in different clinical settings(332), a more recent meta-analysis, in-volving 29 studies and over 8,000 pa-tients, failed to show any mortality benefitfrom intensive glucose control. Tight glu-cose control did reduce the relative risk ofsepticemia by 26% (333). While this lat-ter meta-analysis investigated strategieswith target blood glucose levels of 80–110 mg/dl (4.4–6.1 mmol/l), studieswith less stringent glucose targets werealso included. Stratification by glucosetarget did not demonstrate any heteroge-neity. The authors of this analysis as wellas an accompanying editorial both recom-mend that glycemic targets in critically illpatients be revisited (328–331).While results from ongoing clinicaltrials are still pending, it is clear that un-controlled hyperglycemia is associatedwith adverse outcomes in critically ill pa-tients and that achieving levels of glucosecontrol below 140 mg/dl are reasonable,provided that protocols that minimizerisk for hypoglycemia are utilized andthat personnel are well educated in thedirect application of these protocols.2. Glycemic targets in hospitalizedpatientsThere is relatively strong evidence fromrandomized controlled trials for a glyce-mic target of blood glucose Ͻ110 mg/dl(6.1 mmol/l) in surgical patients in criticalcare units (328–330). However, in sev-eral studies of critically ill medical pa-tients (330,331,333), the incidence ofsevere hypoglycemia (blood glucose Ͻ40mg/dl) was approximately threefoldgreater in intensively treated patients. Theidentification of hypoglycemia as an inde-pendent risk factor for death in the med-ical ICU population (334) may meritcaution in widely promoting the 80–110mg/dl target range for all critically illpopulations.For patients in general medical-surgical units, the evidence for specificglycemic goals is less definitive. Epidemi-ologic and physiologic data suggest thathigher blood glucose levels are associatedwith worse outcomes, but whether glu-cose is simply a marker of the severity ofunderlying illness or a mediator of ad-verse outcomes is unclear. Glycemic tar-gets similar to those of outpatients may bedifficult to achieve in the hospital due tothe effects of stress hyperglycemia, alterednutritional intake, and multiple interrup-tions to medical care. Blood glucose levelsshown to be associated with improvedoutcomes in these patients (fasting glu-cose Ͻ126 mg/dl and all blood glucosereadings Ͻ180–200 mg/dl) would ap-pear reasonable, if they can be safelyachieved.In both the critical care and noncriti-cal care venue, glycemic goals must takeinto account the individual patient’s situ-ation as well as hospital system supportfor achieving these goals. A continuousquality improvement strategy may facili-tate gradual improvement in mean glyce-mia hospital wide.3. Treatment options in hospitalizedpatientsa. Noninsulin glucose-lowering agents.No large studies have investigated the po-tential roles of various noninsulin glu-cose-lowering agents on outcomes ofhospitalized patients with diabetes. Use ofthe various noninsulin classes in the inpa-tient setting presents some specific issues.The long action of sulfonylureas andtheir predisposition to hypoglycemia inpatients not consuming their normal nu-trition serve as relative contraindicationsto routine use of these agents in the hos-pital (335). While the meglitinides, repa-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S43
  • 32. glinide and neteglinide, theoreticallywould produce less hypoglycemia thansulfonylureas, lack of clinical trial data forthese agents, and the fact that they areprimarily prandial in effect, would pre-clude their use. The major limitation tometformin use in the hospital is a numberof specific contraindications to its use, re-lated to risk of lactic acidosis, many ofwhich occur in the hospital. The mostcommon risk factors for lactic acidosis inmetformin-treated patients are cardiacdisease, including decompensated CHF,hypoperfusion, renal insufficiency, oldage, and chronic pulmonary disease(336). Lactic acidosis is a rare complica-tion in the outpatient setting (337), de-spite the relative frequency of risk factors(338). However, in the hospital the risksof hypoxia, hypoperfusion, and renal in-sufficiency are much higher, and it is pru-dent to avoid the use of metformin inmost patients.TZDs are not suitable for initiation inthe hospital because of their delayed onsetof effect. In addition, they increase intra-vascular volume, a particular problem inthose predisposed to CHF and potentiallya problem for patients with hemody-namic changes related to admission diag-noses (e.g., acute coronary ischemia) orinterventions common in hospitalized pa-tients. Pramlintide and exenatide workmainly by reducing postprandial hyper-glycemia and would therefore not be ap-propriate for patients not eating (nil peros, NPO) or with reduced caloric con-sumption. Furthermore, initiation ofthese drugs in the inpatient setting wouldbe problematic due to alterations in nor-mal food intake and their propensity toinduce nausea initially. There is limitedexperience, and no published data, on theDPP-IV inhibitors in the hospital setting,although there are no specific safety con-cerns. They are mainly effective on post-prandial glucose and therefore wouldhave limited effect in patients who are noteating.In summary, each of the major classesof noninsulin glucose-lowering drugs hassignificant limitations for inpatient use.Additionally, they provide little flexibilityor opportunity for titration in a settingwhere acute changes often demand thesecharacteristics. Therefore, insulin, whenused properly, is preferred for the major-ity of hyperglycemic patients in the hos-pital setting.b. Insulini. Subcutaneous insulin therapy. Subcuta-neous insulin therapy may be used to at-tain glucose control in most hospitalizedpatients with diabetes outside of the crit-ical care arena. The components of thedaily insulin dose requirement can be metby a variety of insulins, depending on theparticular hospital situation. Subcutane-ous insulin therapy should cover bothbasal and nutritional needs and is subdi-vided into scheduled insulin and supple-mental, or correction-dose, insulin.Correction-dose insulin therapy is an im-portant adjunct to scheduled insulin,both as a dose-finding strategy and as asupplement when rapid changes in insu-lin requirements lead to hyperglycemia. Ifcorrection doses are frequently required,the appropriate scheduled insulin dosesshould be increased to accommodate theincreased insulin needs. There are cur-rently no published studies comparinghuman regular insulin with rapid-actinganalogs for use as correction-dose insulin.The traditional “sliding-scale” insulinregimens, usually consisting of regular in-sulin without any intermediate or long-acting insulins, have been shown to beineffective when used as monotherapy inpatients with an established insulin re-quirement (339–341). Problems withsliding-scale insulin regimens include thefact that the sliding-scale regimen pre-scribed on admission is likely to be usedthroughout the hospital stay withoutmodification, even when control remainspoor. Additionally, sliding-scale insulintherapy treats hyperglycemia after it hasalready occurred, instead of preventingthe occurrence of hyperglycemia. This“reactive” approach can lead to rapidchanges in blood glucose levels, whichmay exacerbate both hyper- and hypogly-cemia.A recent study demonstrated thesafety and efficacy of using basal-bolus in-sulin therapy utilizing weight-based dos-ing in insulin-naïve hospitalized patientswith type 2 diabetes (342). Glycemic con-trol, defined as a mean blood glucoseϽ140 mg/dl, was achieved in 68% of pa-tients receiving basal-bolus insulin versusonly 38% of those receiving sliding-scaleinsulin alone. There were no differencesin hypoglycemia between the two groups.It is important to note that the patients inthis study were obese, and the doses usedin this study (0.4 to 0.5 units ⅐ kg ⅐ dayϪ1)are higher than what may be required inpatients who are more sensitive to insulin,such as those who are lean or who havetype 1 diabetes.ii. Intravenous insulin infusion. The onlymethod of insulin delivery specifically de-veloped for use in the hospital is contin-uous intravenous infusion, using regularcrystalline insulin. There is no advantageto using rapid acting analogs, whosestructural modifications increase the rateof absorption from subcutaneous depots,in an intravenous insulin infusion. Themedical literature supports the use of in-travenous insulin infusion in preferenceto the subcutaneous route of insulin ad-ministration for several clinical indica-tions among nonpregnant adults. Theseinclude DKA and nonketotic hyperosmo-lar state; general preoperative, intraoper-ative, and postoperative care; thepostoperative period following heart sur-gery; following organ transplantation;with cardiogenic shock; exacerbated hy-perglycemia during high-dose glucocorti-coid therapy; type 1 patients who areNPO; or in critical care illness in general.It may be used as a dose-finding strategyin anticipation of initiation or reinitiationof subcutaneous insulin therapy in type 1or type 2 diabetes.Many institutions use insulin infusionalgorithms that can be implemented bynursing staff. Although numerous algo-rithms have been published, there havebeen no head-to-head comparisons be-tween insulin infusion strategies. Algo-rithms should incorporate the conceptsthat maintenance requirements differ be-tween patients and change over thecourse of treatment. Ideally, intravenousinsulin algorithms should consider bothcurrent and previous glucose levels, therate of change of plasma glucose, and thecurrent intravenous insulin infusion rate.For all algorithms, frequent (Q 1–2 h)bedside glucose testing is required.iii. Transition from intravenous to subcuta-neous insulin therapy. For those who willrequire subcutaneous insulin, the veryshort half-life of intravenous insulin ne-cessitates administering the first dose ofsubcutaneous insulin before discontinua-tion of the intravenous insulin infusion. Ifshort or rapid-acting insulin is used, itshould be injected 1–2 h before stoppingthe infusion. If intermediate- or long-acting insulin is used alone, it should beinjected 2–3 h before. A combination ofshort/rapid- and intermediate/long-acting insulin is usually preferred. Basalinsulin therapy can be initiated at anytime of the day and should not be with-held to await a specific dosing time, suchas bedtime. A recent clinical trial demon-strated that a regimen using 80% of theintravenous insulin requirement over thepreceding 24 h, divided into basal andStandards of Medical CareS44 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 33. bolus insulin components, was effectiveat achieving blood glucose levels between80 and 150 mg/dl following discontinua-tion of the intravenous insulin (343).4. Self-management in the hospitalSelf-management of diabetes in the hos-pital may be appropriate for competentadult patients who have a stable level ofconsciousness, have reasonably stabledaily insulin requirements, successfullyconduct self-management of diabetes athome, have physical skills needed to suc-cessfully self-administer insulin and per-form SMBG, have adequate oral intake,and are proficient in carbohydrate count-ing, use of multiple daily insulin injec-tions or insulin pump therapy, and sick-day management. The patient andphysician, in consultation with nursingstaff, must agree that patient self-management is appropriate under theconditions of hospitalization. For patientsconducting self-management in the hos-pital, it is imperative that basal, prandial,and correction doses of insulin and resultsof bedside glucose monitoring be re-corded as part of the patient’s hospitalmedical record. While many institutionsallow patients on insulin pumps to con-tinue these devices in the hospital, othersexpress concern regarding use of a deviceunfamiliar to staff, particularly in patientswho are not able to manage their ownpump therapy. If a patient is too ill toself-manage either multiple daily injec-tions or CSII, then appropriate subcuta-neous doses can be calculated on the basisof their basal and bolus insulin needs dur-ing hospitalization, with adjustments forchanges in nutritional or metabolic status.5. Preventing hypoglycemiaHypoglycemia, especially in insulin-treated patients, is the leading limitingfactor in the glycemic management oftype 1 and type 2 diabetes (146). In thehospital, multiple additional risk factorsfor hypoglycemia are present, evenamong patients who are neither “brittle”nor tightly controlled. Patients with orwithout diabetes may experience hypo-glycemia in the hospital in associationwith altered nutritional state, heart fail-ure, renal or liver disease, malignancy, in-fection, or sepsis (344,345). Additionaltriggering events leading to iatrogenic hy-poglycemia include sudden reduction ofcorticosteroid dose, altered ability of thepatient to self-report symptoms, reduc-tion of oral intake, emesis, new NPO sta-tus, inappropriate timing of short- orrapid-acting insulin in relation to meals,reduction of rate of administration of in-travenous dextrose, and unexpectedinterruption of enteral feedings or paren-teral nutrition.Despite the preventable nature ofmany inpatient episodes of hypoglyce-mia, institutions are more likely to havenursing protocols for the treatment of hy-poglycemia than for its prevention.Tracking such episodes and analyzingtheir causes are important quality im-provement activities.6. Diabetes care providers in thehospitalInpatient diabetes management may beeffectively provided by primary care phy-sicians, endocrinologists, or hospitalists,but involvement of appropriately trainedspecialists or specialty teams may reducelength of stay, improve glycemic control,and improve outcomes (346–349). In thecare of diabetes, implementation of stan-dardized order sets for scheduled and cor-rection-dose insulin may reduce relianceon sliding-scale management. A team ap-proach is needed to establish hospitalpathways. To achieve glycemic targetsassociated with improved hospital out-comes, hospitals will need multidisci-plinary support for using insulin infusiontherapy outside of critical care units orwill need to develop protocols for subcu-taneous insulin therapy that effectivelyand safely achieve glycemic targets (350).7. DSME in the hospitalTeaching diabetes self-management topatients in hospitals is a challenging task.Patients are ill, under increased stress re-lated to their hospitalization and diagno-sis, and in an environment not conduciveto learning. Ideally, people with diabetesshould be taught at a time and place con-ducive to learning, as outpatients in a rec-ognized program of diabetes education.For the hospitalized patient, diabetes“survival skills” education is generally afeasible approach. Patients and/or familymembers receive sufficient informationand training to enable safe care at home.Those newly diagnosed with diabetes orwho are new to insulin and/or blood glu-cose monitoring need to be instructedbefore discharge. Those patients hospital-ized because of a crisis related to diabetesmanagement or poor care at home neededucation to prevent subsequent episodesof hospitalization. An assessment of theneed for a home health referral or referralto an outpatient diabetes education pro-gram should be part of discharge plan-ning for all patients.8. MNT in the hospitalHospital diets continue to be ordered bycalorie levels based on the “ADA diet.”However, since 1994 the ADA has not en-dorsed any single meal plan or specifiedpercentages of macronutrients, and theterm “ADA diet” should no longer beused. Current nutrition recommenda-tions advise individualization based ontreatment goals, physiologic parameters,and medication usage. Because of thecomplexity of nutrition issues in the hos-pital, a registered dietitian, knowledge-able and skilled in MNT, should serve asan inpatient team member. The dietitianis responsible for integrating informationabout the patient’s clinical condition, eat-ing, and lifestyle habits and for establish-ing treatment goals in order to determinea realistic plan for nutrition therapy(351,352).9. Bedside blood glucose monitoringImplementing intensive diabetes therapyin the hospital setting requires frequentand accurate blood glucose data. Thismeasure is analogous to an additional “vi-tal sign” for hospitalized patients with di-abetes. Bedside glucose monitoring usingcapillary blood has advantages over labo-ratory venous glucose testing because theresults can be obtained rapidly at the“point of care,” where therapeutic deci-sions are made.Bedside blood glucose testing is usu-ally performed with portable meters thatare similar or identical to devices forhome SMBG. Staff training and ongoingquality control activities are importantcomponents of ensuring accuracy of theresults. Ability to track the occurrence ofhypo- and hyperglycemia is necessary.Results of bedside glucose tests should bereadily available to all members of thecare team.For patients who are eating, com-monly recommended testing frequenciesare premeal and at bedtime. For patientsnot eating, testing every 4–6 h is usuallysufficient for determining correction in-sulin doses. Patients on continuous intra-venous insulin typically require hourlyblood glucose testing until the blood glu-cose levels are stable, then every 2 h.10. Discharge planningIt is important to anticipate the postdis-charge antihyperglycemic regimen in allpatients with diabetes or newly discov-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S45
  • 34. ered hyperglycemia. The optimal pro-gram will need to consider the type andseverity of diabetes, the effects of the pa-tient’s illness on blood glucose levels, andthe capacities and desires of the patient.Smooth transition to outpatient careshould be ensured, especially in thosenew to insulin therapy or in whom thediabetes regimen has been substantiallyaltered during the hospitalization. All pa-tients in whom the diagnosis of diabetes isnew should have, at minimum, “survivalskills” training before discharge. More ex-panded diabetes education can be ar-ranged in the community. For those withhyperglycemia who do not require treat-ment upon discharge, follow-up testingthrough their primary care physicianshould be arranged, since many of theseindividuals are found to have diabeteswhen tested after discharge.B. Diabetes care in the school andday care setting (353)Recommendations● An individualized Diabetes MedicalManagement Plan (DMMP) should bedeveloped by the parent/guardian andthe student’s personal diabetes healthcare team with input from the parent/guardian. (E)● All school staff members who have re-sponsibility for a student with diabetesshould receive training that provides abasic understanding of diabetes and astudent’s needs. (E)● While the school nurse is the coordina-tor and primary provider of diabetescare, a small number of school person-nel should be trained in routine andemergency diabetes procedures (in-cluding monitoring of blood glucoselevels and administration of insulin andglucagon) and in the appropriate re-sponse to high and low blood glucoselevels and should perform these diabe-tes care tasks when the school nurse isnot available to do so. These school per-sonnel need not be health care profes-sionals. (E)● As specified in the DMMP and as devel-opmentally appropriate, the studentwith diabetes should have immediateaccess to diabetes supplies at all timesand should be permitted to self-managehis or her diabetes in the classroom oranywhere the student may be in con-junction with a school activity. Suchself-management should include bloodglucose monitoring and responding toblood glucose levels with needed foodand medication. (E)There are ϳ186,300 individuals Ͻ20years of age with diabetes in the U.S.,most of whom attend school and/or sometype of day care and need knowledgeablestaff to provide a safe environment. De-spite legal protections, including cover-age of children with diabetes underSection 504 of the Rehabilitation Act of1973, the Individuals with DisabilitiesEducation Act, and the Americans withDisabilities Act, children in the schooland day care setting still face discrimina-tion. The ADA position statement on Di-abetes Care in the School and Day CareSetting (353) provides the legal and med-ical justifications for the recommenda-tions provided herein.Appropriate diabetes care in theschool and day care setting is necessaryfor the child’s immediate safety, long-term well-being, and optimal academicperformance. Parents and the health careteam should provide school systems andday care providers with the informationnecessary for children with diabetes toparticipate fully and safely in the school/day care experience by developing an in-dividualized DMMP.The school nurse should be the keycoordinator and provider of care andshould coordinate the training of an ade-quate number of school personnel andensure that if the school nurse is notpresent at least one adult is present who istrained to perform the necessary diabetesprocedures (e.g., blood glucose monitor-ing and insulin and glucagon administra-tion) and provide the appropriateresponse to high and low blood glucoselevels in a timely manner while the stu-dent is at school, on field trips, participat-ing in school-sponsored extracurricularactivities, and on transportation providedby the school or day care facility. Theseschool personnel need not be health careprofessionals.The student with diabetes should haveimmediate access to diabetes supplies at alltimes, with supervision as needed. The stu-dent should be able to obtain a blood glu-cose level and respond to the results asquickly and conveniently as possible in theclassroom or wherever the child is in con-junction with a school-related activity, min-imizing the need for missing instruction intheclassroomandavoidingtheriskofwors-ening hypoglycemia or hyperglycemia if thechild must go somewhere else for treat-ment. The student’s desire for privacy dur-ing blood glucose monitoring and insulinadministration should also be accommo-dated.The ADA and partner organizationshave developed tools for school personnelto provide a safe and nondiscriminatoryeducational environment for all studentswith diabetes (354,355).C. Diabetes care at diabetes camps(356)Recommendations● Each camper should have a standard-ized medical form completed by his/herfamily and the physician managing thediabetes. (E)● Camp medical staff should be led bywith a physician with expertise in man-aging type 1 and type 2 diabetes andinclude nurses (including diabetes ed-ucators and diabetes clinical nurse spe-cialists) and registered dietitians withexpertise in diabetes. (E)● All camp staff, including physicians,nurses, dietitians, and volunteers,should undergo background testing toensure appropriateness in workingwith children. (E)The concept of specialized residential andday camps for children with diabetes hasbecome widespread throughout the U.S.and many other parts of the world. Themission of diabetes camps is to provide acamping experience in a safe environ-ment. An equally important goal is to en-able children with diabetes to meet andshare their experiences with one anotherwhile they learn to be more personallyresponsible for their disease. For this tooccur, a skilled medical and camping staffmust be available to ensure optimal safetyand an integrated camping/educationalexperience.Each camper should have a standard-ized medical form completed by his/herfamily and the physician managing the di-abetes that details the camper’s past med-ical history, immunization record, anddiabetes regimen. The home insulin dos-age should be recorded for each camper,including type(s) of insulin used, numberand timing of injections, and the correc-tion factor and carbohydrate ratios usedfor determining bolus dosages for basal-bolus regimens. Campers using CSIIshould also have their basal rates speci-fied. Because camp is often associatedwith more physical activity than experi-enced at home, the insulin dose may haveto be decreased during camp.Standards of Medical CareS46 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 35. The diabetes camping experience isshort term, with food and activity differ-ent than the home environment. Thus,goals of glycemic control at camp are toavoid extremes in blood glucose levelsrather than attempting optimization of in-tensive glycemic control.During camp, a daily record of thecamper’s progress should be made, in-cluding all blood glucose levels and insu-lin dosages. To ensure safety and optimaldiabetes management, multiple bloodglucose determinations should be madethroughout each 24-h period: beforemeals, at bedtime, after or during pro-longed and strenuous activity, and in themiddle of the night when indicated forprior hypoglycemia. If major alterationsof a camper’s regimen appear to be indi-cated, it is important to discuss this withthe camper and the family in addition tothe child’s local physician. The record ofwhat transpired during camp should bediscussed with the family at the end of thecamp session and a copy sent to thechild’s physician.Each camp should secure a formal re-lationship with a nearby medical facilityso that camp medical staff can refer to thisfacility for prompt treatment of medicalemergencies. ADA requires that the campmedical director be a physician with ex-pertise in managing type 1 and type 2 di-abetes. Nursing staff should includediabetes educators and diabetes clinicalnurse specialists. Registered dietitianswith expertise in diabetes should have in-put into the design of the menu and theeducation program. All camp staff, in-cluding medical, nursing, nutrition, andvolunteer, should undergo backgroundtesting to ensure appropriateness inworking with children.D. Diabetes management incorrectional institutions (357)Recommendations● Correctional staff should be trained inthe recognition, treatment, and appro-priate referral for hypo- and hypergly-cemia, including serious metabolicdecompensation. (E)● Patients with a diagnosis of diabetesshould have a complete medical historyand physical examination by a licensedhealth care provider with prescriptiveauthority in a timely manner upon en-try. Insulin-treated patients shouldhave a capillary blood glucose (CBG)determination within 1–2 h of arrival.Staff should identify patients with type1 diabetes who are at high risk for DKAwith omission of insulin. (E)● Medications and MNT should be con-tinued without interruption upon entryinto the correctional environment. (E)● In the correctional setting, policies andprocedures should enable CBG moni-toring to occur at the frequency neces-sitated by the patient’s glycemic controland diabetes regimen and should re-quire staff to notify a physician of allCBG results outside of a specifiedrange, as determined by the treatingphysician. (E)● For all inter-institutional transfers, amedical transfer summary should betransferred with the patient, and diabe-tes supplies and medication should ac-company the patient. (E)● Correctional staff should begin dis-charge planning with adequate leadtime to ensure continuity of care andfacilitate entry into community diabe-tes care. (E)At any given time, over 2 million peopleare incarcerated in prisons and jails in theU.S., and it is estimated that nearly80,000 of these inmates have diabetes. Inaddition, many more people with diabe-tes pass through the corrections system ina given year.People with diabetes in correctionalfacilities should receive care that meetsnational standards. Correctional institu-tions have unique circumstances thatneed to be considered so that all standardsof care may be achieved. Correctional in-stitutions should have written policiesand procedures for the management ofdiabetes and for training of medical andcorrectional staff in diabetes carepractices.Reception screening should empha-size patient safety. In particular, rapididentification of all insulin-treated indi-viduals with diabetes is essential in orderto identify those at highest risk for hypo-and hyperglycemia and DKA. All insulin-treated patients should have a CBG deter-mination within 1–2 h of arrival. Patientswith a diagnosis of diabetes should have acomplete medical history and physical ex-amination by a licensed health care pro-vider with prescriptive authority in atimely manner. It is essential that medica-tion and MNT be continued without inter-ruption upon entry into the correctionalsystem, as a hiatus in either medication orappropriate nutrition may lead to either se-vere hyper- or hypoglycemia.Patients must have access to prompttreatment of hypo- and hyperglycemia.Correctional staff should be trained in therecognition and treatment of these condi-tions, and appropriate staff should betrained to administer glucagon. Institu-tions should implement a policy requir-ing staff to notify a physician of all CBGresults outside of a specified range, as de-termined by the treating physician.Correctional institutions should havesystems in place to ensure that insulin ad-ministration and meals are coordinated toprevent hypo- and hyperglycemia, takinginto consideration the transport of resi-dents off site and the possibility of emer-gency schedule changes. The frequency ofCBG monitoring will vary by patients’ gly-cemic control and diabetes regimens. Pol-icies and procedures should ensure thatthe health care staff has adequate knowl-edge and skills to direct the managementand education of individuals with diabetes.Patients in jails may be housed for ashort period of time before being trans-ferred or released, and patients in prisonmay be transferred within the system sev-eral times during their incarceration.Transferring a patient with diabetes fromone correctional facility to another re-quires a coordinated effort, as does plan-ning for discharge. The ADA positionstatement on Diabetes Management inCorrectional Institutions (357) should beconsulted for more information on thistopic.E. Emergency and disasterpreparedness (358)Recommendations● People with diabetes should maintain adisaster kit that includes items impor-tant to their diabetes self-managementand continuing medical care. (E)● The kit should be reviewed and replen-ished at least twice yearly. (E)The difficulties encountered by peoplewith diabetes and their health care pro-viders in the wake of Hurricane Katrina(359) highlight the need for people withdiabetes to be prepared for emergencies,whether natural or otherwise, affecting aregion or just their household. Such pre-paredness will lessen the impact an emer-gency may have on their condition. It isrecommended that people with diabeteskeep a waterproof and insulated disasterkit ready with items critically importantto their self-management. These may in-clude glucose testing strips, lancets, and aglucose-testing meter; medications in-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S47
  • 36. cluding insulin in a cool bag; syringes;glucose tabs or gels; antibiotic ointments/creams for external use; glucagon emer-gency kits; and photocopies of relevantmedical information, particularly medi-cation lists and recent lab tests/procedures if available. If possible,prescription numbers should be noted,since many chain pharmacies throughoutthe country will refill medications basedon the prescription number alone. In ad-dition, it may be important to carry a listof contacts for national organizations,such as the American Red Cross and ADA.This disaster kit should be reviewed andreplenished at least twice yearly.IX. DIABETES ANDEMPLOYMENT (360)Recommendations● When questions arise about the medi-cal fitness of a person with diabetes fora particular job, a health care professionalwith expertise in treating diabetes shouldperform an individualized assessment;input from the treating physician shouldalways be included. (E)● Proper safety assessments for employ-ment should include review of bloodglucose test results, history of severehypoglycemia, presence of hypoglyce-mia unawareness, and presence of dia-betes-related complications but shouldnot include urine glucose or A1C/eAGtests or be based on a general assess-ment of level of control. (E)Any person with diabetes, whether insu-lin treated or noninsulin treated, shouldbe eligible for any employment for whichhe/she is otherwise qualified. Questionsare sometimes raised by employers aboutthe safety and effectiveness of individualswith diabetes in a given job. When suchquestions are legitimately raised, a personwith diabetes should be individually as-sessed by a health care professional withexpertise in diabetes to determinewhether or not that person can safely andeffectively perform the particular duties ofthe job in question.Employment decisions should neverbe based on generalizations or stereotypesregarding the effects of diabetes. “Blanketbans” that restrict individuals with diabe-tes from certain jobs or classes of employ-ment solely because of the diagnosis ofdiabetes or the use of insulin are medi-cally and legally inappropriate and ignorethe many advancements in diabetes man-agement that range from the types ofmedications used to the tools used to ad-minister them and to monitor blood glu-cose levels. For most types ofemployment, there is no reason to believethat the individual’s diabetes will put em-ployees or the public at risk. In certainsafety-sensitive positions the safety con-cern is whether the employee will becomesuddenly disoriented or incapacitated.Episodes of severe hypoglycemia shouldbe examined by a health care professionalwith expertise in diabetes to determineany impact on safe performance of thejob. Hyperglycemia is not typically a bar-rier to employment unless long-termcomplications are present that interferewith the performance of the job.Most accommodations that help anindividual with diabetes do his or her jobmay be provided easily and with little orno cost to the employer. Typical accom-modations include breaks to test bloodglucose, administer insulin, or accessfood and beverages. Some individualsmay need leave or a flexible work sched-ule or accommodations for diabetes-related complications.The ADA position statement on Dia-betes and Employment should be con-sulted for more information on this topic.X. THIRD-PARTYREIMBURSEMENT FORDIABETES CARE, SELF-MANAGEMENTEDUCATION, ANDSUPPLIES (361)Recommendations● Patients and practitioners should haveaccess to all classes of antidiabetic med-ications, equipment, and supplies with-out undue controls. (E)● MNT and DSME should be covered byinsurance and other payors. (E)To achieve optimal glucose control, theperson with diabetes must be able to ac-cess health care providers who have ex-pertise in the field of diabetes. Treatmentsand therapies that improve glycemic con-trol and reduce the complications of dia-betes will also significantly reduce healthcare costs. Access to the integral compo-nents of diabetes care, such as health carevisits, diabetes supplies and medications,and self-management education, is essen-tial. All medications and supplies, such assyringes, strips, and meters, related to thedaily care of diabetes must also be reim-bursed by third-party payors.It is recognized that the use of formu-laries, prior authorization, and provisionssuch as competitive bidding can manageprovider practices as well as costs to thepotential benefit of payors and patients.However, any controls should ensure thatall classes of anti-diabetic agents withunique mechanisms of action and allclasses of equipment and supplies de-signed for use with such equipment areavailable to facilitate achieving glycemicgoals and to reduce the risk of complica-tions. Without appropriate safeguards,undue controls could constitute an ob-struction of effective care.Medicare and many other third-partypayors cover DSME (Centers for Medicareand Medicaid Services [CMS] term is dia-betes self-management training [DSMT])that meets the national standards forDSME (107) and MNT. The qualifiedbeneficiary, with referral from the pro-vider managing his or her diabetes, canreceive an initial benefit of 10 h of DSMTand 3 h of MNT, with a potential total of13 h of initial. More information on Medi-care policy, including follow-up benefits,is available at or on the CMS Web sites:DSME,; and diabetes MNT,,reimbursement.XI. STRATEGIES FORIMPROVING DIABETESCAREThe implementation of the standards ofcare for diabetes has been suboptimal inmost clinical settings. A recent report(362) indicated that only 37% of adultswith diagnosed diabetes achieved an A1Cof Ͻ7%, only 36% had a blood pressureϽ130/80 mmHg, and just 48% had a totalcholesterol Ͻ200 mg/dl. Most distressingwas that only 7.3% of people with diabe-tes achieved all three treatment goals.While numerous interventions to im-prove adherence to the recommendedstandards have been implemented, thechallenge of providing uniformly effectivediabetes care has thus far defied a simplesolution. A major contributor to subopti-mal care is a delivery system that too oftenis fragmented, lacks clinical informationcapabilities, often duplicates services, andis poorly designed for the delivery ofchronic care. The Institute of Medicinehas called for changes so that delivery sys-tems provide care that is evidence based,patient centered, and systems orientedand takes advantage of information tech-Standards of Medical CareS48 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 37. nologies that foster continuous qualityimprovement. Collaborative, multidisci-plinary teams should be best suited toprovide such care for people with chronicconditions like diabetes and to empowerpatients’ performance of appropriate self-management. Alterations in reimburse-ment that reward the provision of qualitycare, as defined by the attainment of qual-ity measures developed by such programsas the ADA/National Committee for Qual-ity Assurance Diabetes Provider Recogni-tion Program will also be required toachieve desired outcome goals.The NDEP recently launched a newonline resource to help health care profes-sionals better organize their diabetes care.The www.betterdiabetescare.nih.govWeb site should help users design andimplement more effective health care de-livery systems for those with diabetes.In recent years, numerous health careorganizations, ranging from large healthcare systems such as the U.S. Veterans Ad-ministration to small private practices,have implemented strategies to improvediabetes care. Successful programs havepublished results showing improvementin process measures such as measurementof A1C, lipids, and blood pressure. Effectson important intermediate outcomes,such as mean A1C for populations, havebeen more difficult to demonstrate (363–365), although examples do exist (366–370). Successful interventions have beenfocused at the level of health care profes-sionals, delivery systems, and patients.Features of successful programs reportedin the literature include:● Improving health care professional ed-ucation regarding the standards of carethrough formal and informal educationprograms.● Delivery of DSME, which has beenshown to increase adherence to stan-dard of care.● Adoption of practice guidelines, withparticipation of health care profession-als in the process. Guidelines should bereadily accessible at the point of service,such as on patient charts, in examiningrooms, in “wallet or pocket cards,” onPDAs, or on office computer systems.Guidelines should begin with a sum-mary of their major recommendationsinstructing health care professionalswhat to do and how to do it.● Use of checklists that mirror guidelineshave been successful at improving ad-herence to standards of care.● Systems changes, such as provision ofautomated reminders to health careprofessionals and patients, reporting ofprocess and outcome data to providers,and especially identification of patientsat risk because of failure to achieve tar-get values or a lack of reported values.● Quality improvement programs com-bining continuous quality improve-ment or other cycles of analysis andintervention with provider perfor-mance data.● Practice changes, such as clustering ofdedicated diabetes visits into specifictimes within a primary care practiceschedule and/or visits with multiplehealth care professionals on a single dayand group visits.● Tracking systems with either an elec-tronic medical record or patient regis-try have been helpful at increasingadherence to standards of care by pro-spectively identifying those requiringassessments and/or treatment modifi-cations. They likely could have greaterefficacy if they suggested specific ther-apeutic interventions to be consideredfor a particular patient at a particularpoint in time (371).● A variety of nonautomated systems,such as mailing reminders to patients,chart stickers, and flow sheets, havebeen useful to prompt both providersand patients.● Availability of case or (preferably) caremanagement services, usually by anurse (372). Nurses, pharmacists, andother nonphysician health care profes-sionals using detailed algorithms work-ing under the supervision of physiciansand/or nurse education calls have alsobeen helpful. Similarly, dietitians usingMNT guidelines have been demon-strated to improve glycemic control.● Availability and involvement of expertconsultants, such as endocrinologistsand diabetes educators.Evidence suggests that these individualinitiatives work best when provided ascomponents of a multifactorial interven-tion. Therefore, it is difficult to assessthe contribution of each component;however, it is clear that optimal diabetesmanagement requires an organized,systematic approach and involvementof a coordinated team of health careprofessionals.References1. American Diabetes Association: MedicalManagement of Type 1 Diabetes. 5th ed.Alexandria, VA, American Diabetes As-sociation, 20082. American Diabetes Association: MedicalManagement of Type 2 Diabetes. 6th ed.Alexandria, VA, American Diabetes As-sociation, 20083. American Diabetes Association: IntensiveDiabetes Management. Alexandria, VA,American Diabetes Association, 20034. Expert Committee on the Diagnosis andClassification of Diabetes Mellitus: Re-port of the Expert Committee on the Di-agnosis and Classification of DiabetesMellitus. Diabetes Care 20:1183–1197,19975. Expert Committee on the Diagnosis andClassification of Diabetes Mellitus: Fol-low-up report on the diagnosis of diabe-tes mellitus. Diabetes Care 26:3160–3167, 20036. Davidson MB, Schriger DL, Peters AL,Lorber B: Relationship between fastingplasma glucose and glycosylated hemo-globin: potential for false-positive diag-noses of type 2 diabetes using newdiagnostic criteria. JAMA 281:1203–1210, 19997. Nathan DM, Davidson MB, DeFronzoRA, Heine RJ, Henry RR, Pratley R, Zin-man B: Impaired fasting glucose and im-paired glucose tolerance: implicationsfor care. Diabetes Care 30:753–759,20078. Engelgau MM, Narayan KM, HermanWH: Screening for type 2 diabetes. Dia-betes Care 23:1563–1580, 20009. Gabir MM, Hanson RL, Dabelea D, Im-peratore G, Roumain J, Bennett PH,Knowler WC: The 1997 American Dia-betes Association and 1999 WorldHealth Organization criteria for hyper-glycemia in the diagnosis and predictionof diabetes. Diabetes Care 23:1108–1112, 200010. Knowler WC, Barrett-Connor E, FowlerSE, Hamman RF, Lachin JM, Walker EA,Nathan DM: Reduction in the incidenceof type 2 diabetes with lifestyle interven-tion or metformin. N Engl J Med 346:393–403, 200211. Tuomilehto J, Lindstrom J, Eriksson JG,Valle TT, Hamalainen H, Ilanne-ParikkaP, Keinanen-Kiukaanniemi S, Laakso M,Louheranta A, Rastas M, Salminen V,Uusitupa M: Prevention of type 2 diabe-tes mellitus by changes in lifestyleamong subjects with impaired glucosetolerance. N Engl J Med 344:1343–1350,200112. Pan XR, Li GW, Hu YH, Wang JX, YangWY, An ZX, Hu ZX, Lin J, Xiao JZ, CaoHB, Liu PA, Jiang XG, Jiang YY, Wang JP,Zheng H, Zhang H, Bennett PH, HowardBV: Effects of diet and exercise in pre-venting NIDDM in people with impairedglucose tolerance: the Da Qing IGT andDiabetes Study. Diabetes Care 20:537–544, 1997Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S49
  • 38. 13. Buchanan TA, Xiang AH, Peters RK, KjosSL, Marroquin A, Goico J, Ochoa C, TanS, Berkowitz K, Hodis HN, Azen SP:Preservation of pancreatic ␤-cell func-tion and prevention of type 2 diabetes bypharmacological treatment of insulin re-sistance in high-risk hispanic women.Diabetes 51:2796–2803, 200214. Chiasson JL, Josse RG, Gomis R,Hanefeld M, Karasik A, Laakso M: Acar-bose for prevention of type 2 diabetesmellitus: the STOP-NIDDM randomisedtrial. Lancet 359:2072–2077, 200215. Gerstein HC, Yusuf S, Bosch J, Pogue J,Sheridan P, Dinccag N, Hanefeld M,Hoogwerf B, Laakso M, Mohan V, ShawJ, Zinman B, Holman RR: Effect of ros-iglitazone on the frequency of diabetes inpatients with impaired glucose toleranceor impaired fasting glucose: a random-ised controlled trial. Lancet 368:1096–1105, 200616. Ramachandran A, Snehalatha C, Mary S,Mukesh B, Bhaskar AD, Vijay V: The In-dian Diabetes Prevention Programmeshows that lifestyle modification andmetformin prevent type 2 diabetes inAsian Indian subjects with impaired glu-cose tolerance (IDPP-1). Diabetologia 49:289–297, 200617. Johnson SL, Tabaei BP, Herman WH:The efficacy and cost of alternative strat-egies for systematic screening for type 2diabetes in the U.S. population 45–74years of age. Diabetes Care 28:307–311,200518. Harris R, Donahue K, Rathore SS, FrameP, Woolf SH, Lohr KN: Screening adultsfor type 2 diabetes: a review of the evi-dence for the U.S. Preventive ServicesTask Force. Ann Intern Med 138:215–229, 200319. USPSTF: Screening for type 2 diabetesmellitus in adults: recommendationsand rationale. Ann Intern Med 138:212–214, 200320. Dabelea D, Bell RA, D’Agostino RB Jr,Imperatore G, Johansen JM, Linder B,Liu LL, Loots B, Marcovina S, Mayer-Davis EJ, Pettitt DJ, Waitzfelder B: Inci-dence of diabetes in youth in the UnitedStates. JAMA 297:2716–2724, 200721. Liese AD, D’Agostino RB Jr, HammanRF, Kilgo PD, Lawrence JM, Liu LL,Loots B, Linder B, Marcovina S, Rodri-guez B, Standiford D, Williams DE: Theburden of diabetes mellitus among USyouth: prevalence estimates from theSEARCH for Diabetes in Youth Study.Pediatrics 118:1510–1518, 200622. American Diabetes Association: Type 2diabetes in children and adolescents(Consensus Statement). Diabetes Care23:381–389, 200023. American Diabetes Association: Gesta-tional diabetes mellitus (Position State-ment). Diabetes Care 27 (Suppl. 1):S88–S90, 200424. Metzger BE, Lowe LP, Dyer AR, TrimbleER, Chaovarindr U, Coustan DR, Had-den DR, McCance DR, Hod M, McIntyreHD, Oats JJ, Persson B, Rogers MS, SacksDA: Hyperglycemia and adverse preg-nancy outcomes. N Engl J Med 358:1991–2002, 200825. Kim C, Newton KM, Knopp RH: Gesta-tional diabetes and the incidence of type2 diabetes: a systematic review. DiabetesCare 25:1862–1868, 200226. Lindstrom J, Ilanne-Parikka P, PeltonenM, Aunola S, Eriksson JG, Hemio K, Ha-malainen H, Harkonen P, Keinanen-Kiukaanniemi S, Laakso M, LouherantaA, Mannelin M, Paturi M, Sundvall J,Valle TT, Uusitupa M, Tuomilehto J:Sustained reduction in the incidence oftype 2 diabetes by lifestyle intervention:follow-up of the Finnish Diabetes Pre-vention Study. Lancet 368:1673–1679,200627. Li G, Zhang P, Wang J, Gregg EW, YangW, Gong Q, Li H, Li H, Jiang Y, An Y,Shuai Y, Zhang B, Zhang J, ThompsonTJ, Gerzoff RB, Roglic G, Hu Y, BennettPH: The long-term effect of lifestyle in-terventions to prevent diabetes in theChina Da Qing Diabetes PreventionStudy: a 20-year follow-up study. Lancet371:1783–1789, 200828. Kosaka K, Noda M, Kuzuya T: Preven-tion of type 2 diabetes by lifestyle inter-vention: a Japanese trial in IGT males.Diabetes Res Clin Pract 67:152–162,200529. Torgerson JS, Hauptman J, Boldrin MN,Sjostrom L: XENical in the prevention ofdiabetes in obese subjects (XENDOS)study: a randomized study of orlistat asan adjunct to lifestyle changes for theprevention of type 2 diabetes in obesepatients. Diabetes Care 27:155–161,200430. Gerstein HC: Point: If it is important toprevent type 2 diabetes, it is important toconsider all proven therapies within acomprehensive approach. Diabetes Care30:432–434, 200731. American Diabetes Association: Consen-sus statement on self-monitoring ofblood glucose. Diabetes Care 10:95–99,198732. American Diabetes Asociation: Self-monitoring of blood glucose. DiabetesCare 17:81–86, 199433. Welschen LM, Bloemendal E, Nijpels G,Dekker JM, Heine RJ, Stalman WA,Bouter LM: Self-monitoring of bloodglucose in patients with type 2 diabeteswho are not using insulin: a systematicreview. Diabetes Care 28:1510–1517,200534. Farmer A, Wade A, Goyder E, Yudkin P,French D, Craven A, Holman R, Kin-month AL, Neil A: Impact of self moni-toring of blood glucose in themanagement of patients with non-insu-lin treated diabetes: open parallel grouprandomised trial. BMJ 335:132, 200735. O’Kane MJ, Bunting B, Copeland M,Coates VE: Efficacy of self monitoring ofblood glucose in patients with newly di-agnosed type 2 diabetes (ESMONstudy): randomised controlled trial. BMJ336:1174–1177, 200836. Simon J, Gray A, Clarke P, Wade A, NeilA, Farmer A: Cost effectiveness of selfmonitoring of blood glucose in patientswith non-insulin treated type 2 diabetes:economic evaluation of data from the Di-GEM trial. BMJ 336:1177–1180, 200837. Sacks DB, Bruns DE, Goldstein DE, Ma-claren NK, McDonald JM, Parrott M:Guidelines and recommendations forlaboratory analysis in the diagnosis andmanagement of diabetes mellitus. ClinChem 48:436–472, 200238. The Juvenile Diabetes Research Founda-tion Continuous Glucose MonitoringStudy Group: Continuous glucose mon-itoring and intensive treatment of type 1diabetes. N Engl J Med 359:1464–1476,200839. Stratton IM, Adler AI, Neil HA, Mat-thews DR, Manley SE, Cull CA, HaddenD, Turner RC, Holman RR: Associationof glycaemia with macrovascular andmicrovascular complications of type 2diabetes (UKPDS 35): prospective ob-servational study. BMJ 321:405–412,200040. Cagliero E, Levina EV, Nathan DM: Im-mediate feedback of HbA1c levels im-proves glycemic control in type 1 andinsulin-treated type 2 diabetic patients.Diabetes Care 22:1785–1789, 199941. Miller CD, Barnes CS, Phillips LS, Zie-mer DC, Gallina DL, Cook CB, MarymanSD, El Kebbi IM: Rapid A1c availabilityimproves clinical decision-making in anurban primary care clinic. Diabetes Care26:1158–1163, 200342. Nathan DM, Kuenen J, Borg R, Zheng H,Schoenfeld D, Heine RJ: Translating theA1C assay into estimated average glu-cose values. Diabetes Care 31:1473–1478, 200843. Rohlfing CL, Wiedmeyer HM, Little RR,England JD, Tennill A, Goldstein DE:Defining the relationship betweenplasma glucose and HbA(1c): analysis ofglucose profiles and HbA(1c) in the Di-abetes Control and Complications Trial.Diabetes Care 25:275–278, 200244. Wilson DM, Kollman: Relationship ofA1C to glucose concentrations in chil-dren with type 1 diabetes: assessmentsby high-frequency glucose determina-tions by sensors. Diabetes Care 31:381–385, 200845. The effect of intensive treatment of dia-betes on the development and progres-sion of long-term complications ininsulin-dependent diabetes mellitus.The Diabetes Control and Complica-Standards of Medical CareS50 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 39. tions Trial Research Group. N Engl J Med329:977–986, 199346. Retinopathy and nephropathy in pa-tients with type 1 diabetes four years af-ter a trial of intensive therapy: theDiabetes Control and ComplicationsTrial/Epidemiology of Diabetes Inter-ventions and Complications ResearchGroup. N Engl J Med 342:381–389, 200047. Martin CL, Albers J, Herman WH,Cleary P, Waberski B, Greene DA,Stevens MJ, Feldman EL: Neuropathyamong the diabetes control and compli-cations trial cohort 8 years after trialcompletion. Diabetes Care 29:340–344,200648. Ohkubo Y, Kishikawa H, Araki E, MiyataT, Isami S, Motoyoshi S, Kojima Y, Fu-ruyoshi N, Shichiri M: Intensive insulintherapy prevents the progression of dia-betic microvascular complications inJapanese patients with non-insulin-dependent diabetes mellitus: a random-ized prospective 6-year study. DiabetesRes Clin Pract 28:103–117, 199549. Effect of intensive blood-glucose controlwith metformin on complications inoverweight patients with type 2 diabetes(UKPDS 34): UK Prospective DiabetesStudy (UKPDS) Group. Lancet 352:854–865, 199850. Intensive blood-glucose control withsulphonylureas or insulin comparedwith conventional treatment and risk ofcomplications in patients with type 2 di-abetes (UKPDS 33): UK Prospective Di-abetes Study (UKPDS) Group. Lancet352:837–853, 199851. Holman RR, Paul SK, Bethel MA, Mat-thews DR, Neil HA: 10-Year follow-up ofintensive glucose control in type 2 dia-betes. N Engl J Med 359:1577–1589,200852. Lawson ML, Gerstein HC, Tsui E, Zin-man B: Effect of intensive therapy onearly macrovascular disease in young in-dividuals with type 1 diabetes: a system-atic review and meta-analysis. DiabetesCare 22 (Suppl. 2):B35–B39, 199953. Selvin E, Marinopoulos S, Berkenblit G,Rami T, Brancati FL, Powe NR, GoldenSH: Meta-analysis: glycosylated hemo-globin and cardiovascular disease in di-abetes mellitus. Ann Intern Med 141:421–431, 200454. Stettler C, Allemann S, Juni P, Cull CA,Holman RR, Egger M, Krahenbuhl S,Diem P: Glycemic control and macro-vascular disease in types 1 and 2 diabetesmellitus: meta-analysis of randomizedtrials. Am Heart J 152:27–38, 200655. Nathan DM, Cleary PA, Backlund JY,Genuth SM, Lachin JM, Orchard TJ,Raskin P, Zinman B: Intensive diabetestreatment and cardiovascular disease inpatients with type 1 diabetes. N EnglJ Med 353:2643–2653, 200556. Gerstein HC, Miller ME, Byington RP,Goff DC Jr, Bigger JT, Buse JB, CushmanWC, Genuth S, Ismail-Beigi F, GrimmRH Jr, Probstfield JL, Simons-MortonDG, Friedewald WT: Effects of intensiveglucose lowering in type 2 diabetes.N Engl J Med 358:2545–2559, 200857. Patel A, MacMahon S, Chalmers J, NealB, Billot L, Woodward M, Marre M, Coo-per M, Glasziou P, Grobbee D, Hamet P,Harrap S, Heller S, Liu L, Mancia G, Mo-gensen CE, Pan C, Poulter N, Rodgers A,Williams B, Bompoint S, De Galan BE,Joshi R, Travert F: Intensive blood glu-cose control and vascular outcomes inpatients with type 2 diabetes. N EnglJ Med 358:2560–2572, 200858. Duckworth W: VADT results. Presentedat the 68th Annual Meeting of the Amer-ican Diabetes Association, 6–10 June2008, at the Moscone Convention Cen-ter, San Francisco, CA59. American Diabetes Association: Post-prandial blood glucose (ConsensusStatement). Diabetes Care 24:775–778,200160. Ceriello A, Taboga C, Tonutti L, Quagli-aro L, Piconi L, Bais B, Da Ros R, Motz E:Evidence for an independent and cumu-lative effect of postprandial hypertri-glyceridemia and hyperglycemia onendothelial dysfunction and oxidativestress generation: effects of short- andlong-term simvastatin treatment. Circu-lation 106:1211–1218, 200261. Metzger BE, Buchanan TA, Coustan DR,de Leiva A, Dunger DB, Hadden DR,Hod M, Kitzmiller JL, Kjos SL, Oats JN,Pettitt DJ, Sacks DA, Zoupas C: Sum-mary and recommendations of the FifthInternational Workshop-Conference onGestational Diabetes Mellitus. DiabetesCare 30 (Suppl. 2):S251–S260, 200762. Kitzmiller JL, Block JM, Brown FM,Catalano PM, Conway DL, Coustan DR,Gunderson EP, Herman WH, HoffmanLD, Inturrisi M, Jovanovic LB, Kjos SI,Knopp RH, Montoro MN, Ogata ES,Paramsothy P, Reader DM, Rosenn BM,Thomas AM, Kirkman MS: Managingpreexisting diabetes for pregnancy: sum-mary of evidence and consensus recom-mendations for care. Diabetes Care 31:1060–1079, 200863. DeWitt DE, Hirsch IB: Outpatient insu-lin therapy in type 1 and type 2 diabetesmellitus: scientific review. JAMA 289:2254–2264, 200364. Rosenstock J, Dailey G, Massi-BenedettiM, Fritsche A, Lin Z, Salzman A: Re-duced hypoglycemia risk with insulinglargine: a meta-analysis comparing in-sulin glargine with human NPH insulinintype2diabetes.DiabetesCare28:950–955, 200565. Mooradian AD, Bernbaum M, Albert SG:Narrative review: a rational approach tostarting insulin therapy. Ann Intern Med145:125–134, 200666. Nathan DM, Buse JB, Davidson MB,Heine RJ, Holman RR, Sherwin R, Zin-man B: Management of hyperglycemia intype 2 diabetes: a consensus algorithmfor the initiation and adjustment of ther-apy: a consensus statement from theAmerican Diabetes Association and theEuropean Association for the Study ofDiabetes. Diabetes Care 29:1963–1972,200667. Nathan DM, Buse JB, Davidson MB, Fer-rannini E, Holman RR, Sherwin R, andZinman B: Medical management of hy-perglycemia in type 2 diabetes: a consen-sus algorithm for the initiation andadjustment of therapy: a consensusstatement of the American Diabetes As-sociation and the European Associationfor the Study of Diabetes. Diabetes Care32:193–203, 200968. American Diabetes Association: Nutri-tion recommendations and interven-tions for diabetes—2006. Diabetes Care29:2140–2157, 200669. DAFNE Study Group: Training in flexi-ble, intensive insulin management to en-able dietary freedom in people with type1 diabetes: dose adjustment for normaleating (DAFNE) randomised controlledtrial. BMJ 325:746, 200270. Franz MJ, Monk A, Barry B, McClain K,Weaver T, Cooper N, Upham P, Bergen-stal R, Mazze RS: Effectiveness of medi-cal nutrition therapy provided bydietitians in the management of non-in-sulin-dependent diabetes mellitus: arandomized, controlled clinical trial. JAm Diet Assoc 95:1009–1017, 199571. Goldhaber-Fiebert JD, Goldhaber-FiebertSN, Tristan ML, Nathan DM: Randomizedcontrolled community-based nutritionand exercise intervention improves glyce-mia and cardiovascular risk factors in type2 diabetic patients in rural Costa Rica. Di-abetes Care 26:24–29, 200372. Lemon CC, Lacey K, Lohse B, HubacherDO, Klawitter B, Palta M: Outcomesmonitoring of health, behavior, andquality of life after nutrition interventionin adults with type 2 diabetes. J Am DietAssoc 104:1805–1815, 200473. Miller CK, Edwards L, Kissling G, San-ville L: Nutrition education improvesmetabolic outcomes among older adultswith diabetes mellitus: results from arandomized controlled trial. Prev Med34:252–259, 200274. Wilson C, Brown T, Acton K, Gilliland S:Effects of clinical nutrition educationand educator discipline on glycemiccontrol outcomes in the Indian healthservice. Diabetes Care 26:2500–2504,200375. Graber AL, Elasy TA, Quinn D, Wolff K,Brown A: Improving glycemic control inadults with diabetes mellitus: shared re-sponsibility in primary care practices.South Med J 95:684–690, 2002Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S51
  • 40. 76. Gaetke LM, Stuart MA, Truszczynska H:A single nutrition counseling sessionwith a registered dietitian improvesshort-term clinical outcomes for ruralKentucky patients with chronic diseases.J Am Diet Assoc 106:109–112, 200677. Yu-Poth S, Zhao G, Etherton T, NaglakM, Jonnalagadda S, Kris-Etherton PM:Effects of the National Cholesterol Edu-cation Program’s Step I and Step II di-etary intervention programs oncardiovascular disease risk factors: ameta-analysis. Am J Clin Nutr 69:632–646, 199978. Van Horn L, McCoin M, Kris-EthertonPM, Burke F, Carson JA, ChampagneCM, Karmally W, Sikand G: The evi-dence for dietary prevention and treat-ment of cardiovascular disease. J Am DietAssoc 108:287–331, 200879. Appel LJ, Moore TJ, Obarzanek E,Vollmer WM, Svetkey LP, Sacks FM,Bray GA, Vogt TM, Cutler JA, Wind-hauser MM, Lin PH, Karanja N: A clini-cal trial of the effects of dietary patternson blood pressure: DASH CollaborativeResearch Group. N Engl J Med336:1117–1124, 199780. Norris SL, Zhang X, Avenell A, Gregg E,Bowman B, Schmid CH, Lau J: Long-term effectiveness of weight-loss inter-ventions in adults with pre-diabetes: areview. Am J Prev Med 28:126–139,200581. Klein S, Sheard NF, Pi-Sunyer X, Daly A,Wylie-Rosett J, Kulkarni K, Clark NG:Weight management through lifestylemodification for the prevention andmanagement of type 2 diabetes: ratio-nale and strategies: a statement of theAmerican Diabetes Association, theNorth American Association for theStudy of Obesity, and the American So-ciety for Clinical Nutrition. DiabetesCare 27:2067–2073, 200482. Norris SL, Zhang X, Avenell A, Gregg E,Schmid CH, Kim C, Lau J: Efficacy ofpharmacotherapy for weight loss inadults with type 2 diabetes mellitus: ameta-analysis. Arch Intern Med 164:1395–1404, 200483. Wolf AM, Conaway MR, Crowther JQ,Hazen KY, Nadler L, Oneida B, BovbjergVE: Translating lifestyle intervention topractice in obese patients with type 2diabetes: Improving Control with Activ-ity and Nutrition (ICAN) study. DiabetesCare 27:1570–1576, 200484. Manning RM, Jung RT, Leese GP, New-ton RW: The comparison of four weightreduction strategies aimed at overweightpatients with diabetes mellitus: four-year follow-up. Diabet Med 15:497–502,199885. Shai I, Schwarzfuchs D, Henkin Y, Sha-har DR, Witkow S, Greenberg I, GolanR, Fraser D, Bolotin A, Vardi H, Tangi-Rozental O, Zuk-Ramot R, Sarusi B,Brickner D, Schwartz Z, Sheiner E,Marko R, Katorza E, Thiery J, FiedlerGM, Bluher M, Stumvoll M, StampferMJ: Weight loss with a low-carbohy-drate, Mediterranean, or low-fat diet.N Engl J Med 359:229–241, 200886. Franz MJ, VanWormer JJ, Crain AL,Boucher JL, Histon T, Caplan W, Bow-man JD, Pronk NP: Weight-loss out-comes: a systematic review and meta-analysis of weight-loss clinical trials witha minimum 1-year follow-up. J Am DietAssoc 107:1755–1767, 200787. Pi-Sunyer X, Blackburn G, Brancati FL,Bray GA, Bright R, Clark JM, Curtis JM,Espeland MA, Foreyt JP, Graves K,Haffner SM, Harrison B, Hill JO, HortonES, Jakicic J, Jeffery RW, Johnson KC,Kahn S, Kelley DE, Kitabchi AE,Knowler WC, Lewis CE, Maschak-CareyBJ, Montgomery B, Nathan DM, PatricioJ, Peters A, Redmon JB, Reeves RS, RyanDH, Safford M, Van Dorsten B, WaddenTA, Wagenknecht L, Wesche-ThobabenJ, Wing RR, Yanovski SZ: Reduction inweight and cardiovascular disease riskfactors in individuals with type 2 diabe-tes: 1-year results of the Look AHEADtrial. Diabetes Care 30:1374–1383,200788. Foster GD, Wyatt HR, Hill JO,McGuckin BG, Brill C, Mohammed BS,Szapary PO, Rader DJ, Edman JS, KleinS: A randomized trial of a low-carbohy-drate diet for obesity. N Engl J Med 348:2082–2090, 200389. Stern L, Iqbal N, Seshadri P, ChicanoKL, Daily DA, McGrory J, Williams M,Gracely EJ, Samaha FF: The effects oflow-carbohydrate versus conventionalweight loss diets in severely obeseadults: one-year follow-up of a random-ized trial. Ann Intern Med 140:778–785,200490. Gardner C, Kiazand A, Alhassan S,Soowon K, Stafford R, Balise R, KraemerH, King A: Comparison of the Atkins,Zone, Ornish, and LEARN diets forchange in weight and related risk factorsamong overweight premenopausalwomen JAMA 297:969–977, 200791. Nordmann AJ, Nordmann A, Briel M,Keller U, Yancy WS Jr, Brehm BJ, BucherHC: Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascu-lar risk factors: a meta-analysis ofrandomized controlled trials. Arch InternMed 166:285–293, 200692. Institute of Medicine: Dietary ReferenceIntakes: Energy, Carbohydrate, Fiber, Fat,Fatty Acids, Cholesterol, Protein, andAmino Acids. Washington, D.C., Na-tional Academies Press, 200293. Barnard ND, Cohen J, Jenkins DJ, Turn-er-McGrievy G, Gloede L, Jaster B, SeidlK, Green AA, Talpers S: A low-fat vegandiet improves glycemic control and car-diovascular risk factors in a randomizedclinical trial in individuals with type 2diabetes. Diabetes Care 29:1777–1783,200694. Turner-McGrievy GM, Barnard ND, Co-hen J, Jenkins DJ, Gloede L, Green AA:Changes in nutrient intake and dietaryquality among participants with type 2diabetes following a low-fat vegan diet ora conventional diabetes diet for 22weeks. J Am Diet Assoc 108:1636–1645,200895. Franz MJ, Bantle JP, Beebe CA, BrunzellJD, Chiasson JL, Garg A, HolzmeisterLA, Hoogwerf B, Mayer-Davis E, Moora-dian AD, Purnell JQ, Wheeler M: Evi-dence-based nutrition principles andrecommendations for the treatment andprevention of diabetes and related com-plications. Diabetes Care 25:148–198,200296. Buchwald H, Estok R, Fahrbach K, BanelD, Jensen MD, Pories WJ, Bantle JP,Sledge I: Weight and type 2 diabetes af-ter bariatric surgery: systematic reviewand meta-analysis. Am J Med. In Press97. Dixon JB, O’Brien PE, Playfair J, Chap-man L, Schachter LM, Skinner S, Proi-etto J, Bailey M, Anderson M: Adjustablegastric banding and conventional ther-apy for type 2 diabetes: a randomizedcontrolled trial. JAMA 299:316–323,200898. Buchwald H, Estok R, Fahrbach K, BanelD, Sledge I: Trends in mortality in bari-atric surgery: a systematic review andmeta-analysis. Surgery 142:621–632,200799. Sjostrom L, Narbro K, Sjostrom CD,Karason K, Larsson B, Wedel H, Lystig T,Sullivan M, Bouchard C, Carlsson B,Bengtsson C, Dahlgren S, GummessonA, Jacobson P, Karlsson J, Lindroos AK,Lonroth H, Naslund I, Olbers T, StenlofK, Torgerson J, Agren G, Carlsson LM:Effects of bariatric surgery on mortalityin Swedish obese subjects. N Engl J Med357:741–752, 2007100. Piette JD, Glasgow RE: Sttategies for im-proving behavioral and health outcomesamong people with diabetes: self man-agemnt education. In Evidence-Based Di-abetes Care. Gerstein HC, Hayes RB, Eds.Ontario, Canada, BC Decker, 2000101. Norris SL, Engelgau MM, Narayan KM:Effectiveness of self-management train-ing in type 2 diabetes: a systematic re-view of randomized controlled trials.Diabetes Care 24:561–587, 2001102. Norris SL, Lau J, Smith SJ, Schmid CH,Engelgau MM: Self-management educa-tion for adults with type 2 diabetes: ameta-analysis of the effect on glycemiccontrol. Diabetes Care 25:1159–1171,2002103. Gary TL, Genkinger JM, Guallar E, Pey-rot M, Brancati FL: Meta-analysis of ran-domized educational and behavioralinterventions in type 2 diabetes. DiabetesStandards of Medical CareS52 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 41. Educ 29:488–501, 2003104. Steed L, Cooke D, Newman S: A system-atic review of psychosocial outcomesfollowing education, self-managementand psychological interventions in dia-betes mellitus. Patient Educ Couns 51:5–15, 2003105. Ellis SE, Speroff T, Dittus RS, Brown A,Pichert JW, Elasy TA: Diabetes patienteducation: a meta-analysis and meta-re-gression. Patient Educ Couns 52:97–105,2004106. Warsi A, Wang PS, LaValley MP, AvornJ, Solomon DH: Self-management edu-cation programs in chronic disease: asystematic review and methodologicalcritique of the literature. Arch Intern Med164:1641–1649, 2004107. Funnell MM, Brown TL, Childs BP, HaasLB, Hosey GM, Jensen B, Maryniuk M,Peyrot M, Piette JD, Reader D, SiminerioLM, Weinger K, Weiss MA: Nationalstandards for diabetes self-managementeducation. Diabetes Care 30:1630–1637, 2007108. Mulcahy K, Maryniuk M, Peeples M,Peyrot M, Tomky D, Weaver T, Yarbor-ough P: Diabetes self-management edu-cation core outcomes measures. DiabetesEduc 29: 768- 84:787, 2003109. Glasgow RE, Peeples M, Skovlund SE:Where is the patient in diabetes perfor-mance measures? The case for includingpatient-centered and self-managementmeasures. Diabetes Care 31:1046–1050,2008110. Barker JM, Goehrig SH, Barriga K, Hoff-man M, Slover R, Eisenbarth GS, NorrisJM, Klingensmith GJ, Rewers M: Clinicalcharacteristics of children diagnosedwith type 1 diabetes through intensivescreening and follow-up. Diabetes Care27:1399–1404, 2004111. Rickheim PL, Weaver TW, Flader JL,Kendall DM: Assessment of group versusindividual diabetes education: a ran-domized study. Diabetes Care 25:269–274, 2002112. Trento M, Passera P, Borgo E, TomalinoM, Bajardi M, Cavallo F, Porta M: A5-year randomized controlled study oflearning, problem solving ability, andquality of life modifications in peoplewith type 2 diabetes managed by groupcare. Diabetes Care 27:670–675, 2004113. Norris SL, Chowdhury FM, Van Le K,Horsley T, Brownstein JN, Zhang X, JackL Jr, Satterfield DW: Effectiveness ofcommunity health workers in the care ofpersons with diabetes. Diabet Med 23:544–556, 2006114. Sigal RJ, Kenny GP, Wasserman DH,Castaneda-Sceppa C: Physical activity/exercise and type 2 diabetes. DiabetesCare 27:2518–2539, 2004115. Wasserman DH, Zinman B: Exercise inindividuals with IDDM. Diabetes Care17:924–937, 1994116. Boule´ NG, Haddad E, Kenny GP, WellsGA, Sigal RJ: Effects of exercise on gly-cemic control and body mass in type 2diabetes mellitus: a meta-analysis ofcontrolled clinical trials. JAMA 286:1218–1227, 2001117. Boule´ NG, Kenny GP, Haddad E, WellsGA, Sigal RJ: Meta-analysis of the effectof structured exercise training on cardio-respiratory fitness in type 2 diabetesmellitus. Diabetologia 46:1071–1081,2003118. US Department of Health and HumanServices: Physical Activity and Health: AReport of the Surgeon General. Atlanta,GA, Centers for Disease Control and Pre-vention, 1996119. Ivy JL: Role of exercise training in theprevention and treatment of insulin re-sistance and non-insulin-dependent di-abetes mellitus. Sports Med 24:321–336,1997120. Dunstan DW, Daly RM, Owen N, JolleyD, de Court, Shaw J, Zimmet P: High-intensity resistance training improvesglycemic control in older patients withtype 2 diabetes. Diabetes Care 25:1729–1736, 2002121. Castaneda C, Layne JE, Munoz-OriansL, Gordon PL, Walsmith J, Foldvari M,Roubenoff R, Tucker KL, Nelson ME: Arandomized controlled trial of resistanceexercise training to improve glycemiccontrol in older adults with type 2 dia-betes. Diabetes Care 25:2335–2341,2002122. Sigal RJ, Kenny GP, Boule NG, WellsGA, Prud’homme D, Fortier M, Reid RD,Tulloch H, Coyle D, Phillips P, JenningsA, Jaffey J: Effects of aerobic training, re-sistance training, or both on glycemiccontrol in type 2 diabetes: a randomizedtrial. Ann Intern Med 147:357–369, 2007123. Bax JJ, Young LH, Frye RL, Bonow RO,Steinberg HO, Barrett EJ: Screening forcoronary artery disease in patients withdiabetes. Diabetes Care 30:2729–2736,2007124. Berger M, Berchtold P, Cuppers HJ,Drost H, Kley HK, Muller WA,Wiegelmann W, Zimmerman-TelschowH, Gries FA, Kruskemper HL, Zimmer-mann H: Metabolic and hormonal ef-fects of muscular exercise in juveniletype diabetics. Diabetologia 13:355–365,1977125. American Diabetes Association: Physicalactivity/exercise and diabetes (PositionStatement). Diabetes Care 27 (Suppl. 1):S58–S62, 2004126. Berger M: Adjustment of insulin and oralagent therapy. In Handbook of Exercise inDiabetes. 2nd ed. Ruderman N, DevlinJTSSH, Krisska A, Eds. Alexandria, VA,American Diabetes Association, 2002, p.365–376127. Aiello LP, Wong J, Cavallerano J, BursellSE, Aiello LM: Retinopathy. In Handbookof Exercise in Diabetes. 2nd ed. RudermanN, Devlin JT, Kriska A, Eds. Alexandria,VA, American Diabetes Association,2002, p. 401–413128. Vinik A, Erbas T: Neuropathy. In Hand-book of Exercise in Diabetes. 2nd ed. Ru-derman N, Devlin JT, Kriska A, Eds.Alexnadria, VA, Anerican Diabetes Asso-ciation, 2002, p. 463–496129. Levin ME: The Diabetic Foot. In Hand-book of Exercise in Diabetes. Ruderman N,Devlin JT, Kriska A, Eds. Alexandria,VA, American Diabetes Association,2002, p. 385–399130. Wackers FJ, Young LH, Inzucchi SE,Chyun DA, Davey JA, Barrett EJ,Taillefer R, Wittlin SD, Heller GV, Filip-chuk N, Engel S, Ratner RE, IskandrianAE: Detection of silent myocardial isch-emia in asymptomatic diabetic subjects:the DIAD study. Diabetes Care 27:1954–1961, 2004131. Valensi P, Sachs RN, Harfouche B,Lormeau B, Paries J, Cosson E, Paycha F,Leutenegger M, Attali JR: Predictivevalue of cardiac autonomic neuropathyin diabetic patients with or without si-lent myocardial ischemia. Diabetes Care24:339–343, 2001132. Mogensen CE: Nephropathy. In Hand-book of Exercise in Diabetes. 2nd ed. Ru-derman N, Devlin JT, Kriska A, Eds.Alexandria, VA, American Diabetes As-sociation, 2002, p. 433–449133. Anderson RJ, Grigsby AB, Freedland KE,de Groot M, McGill JB, Clouse RE, Lust-man PJ: Anxiety and poor glycemic con-trol: a meta-analytic review of theliterature. Int J Psychiatry Med 32:235–247, 2002134. Jacobson AM: Depression and diabetes.Diabetes Care 16:1621–1623, 1993135. Rubin RR, Peyrot M: Psychosocial prob-lems and interventions in diabetes: a re-view of the literature. Diabetes Care 15:1640–1657, 1992136. Surwit RS, Schneider MS, Feinglos MN:Stress and diabetes mellitus. DiabetesCare 15:1413–1422, 1992137. Young-Hyman D: Psycosocial factors af-fecting adherence, quality of life, andwell-being: Helping patients cope. InMedical Management of Type 1 Diabetes.4th ed. Bode B, Ed. Alexandria, VA,American Diabetes Association, 2004, p.162–182138. Delahanty LM, Grant RW, Wittenberg E,Bosch JL, Wexler DJ, Cagliero E, MeigsJB: Association of diabetes-related emo-tional distress with diabetes treatment inprimary care patients with type 2 diabe-tes. Diabet Med 24:48–54, 2007139. Anderson BJ, Auslander WF, Jung KC,Miller JP, Santiago JV: Assessing familysharing of diabetes responsibilities. J Pe-diatr Psychol 15:477–492, 1990140. McCulloch DK, Glasgow RE, HampsonSE, Wagner E: A systematic approach toPosition StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S53
  • 42. diabetes management in the post-DCCTera. Diabetes Care 17:765–769, 1994141. Rubin RR, Peyrot M: Psychological is-sues and treatments for people with di-abetes. J ClinPsychol 57:457–478, 2001142. Peyrot M, Rubin RR: Behavioral and psy-chosocial interventions in diabetes: aconceptual review. Diabetes Care 30:2433–2440, 2007143. Lustman PJ, Griffith LS, Clouse RE,Cryer PE: Psychiatric illness in diabetesmellitus: relationship to symptoms andglucose control. J Nerv Ment Dis174:736–742, 1986144. Marcus MD, Wing RR: Eating disordersand diabetes. In Neuropsychological andBehavioral Aspects of Diabetes. HolmesCS, Ed. New York, Springer-Verlag,1990, p. 102–121145. American Diabetes Association: Hyper-glycemic crises in diabetes. Diabetes Care27 (Suppl. 1):S94–S102, 2004146. Cryer PE: Hypoglycaemia: the limitingfactor in the glycaemic management oftype I and type II diabetes. Diabetologia45:937–948, 2002147. Gannon MC, Nuttall FQ: Protein and di-abetes. In American Diabetes AssociationGuide to Medical Nutrition Therapy forDiabetes. Franz MJ, Bantle JP, Eds. Alex-andria, VA, American Diabetes Associa-tion, 1999, p. 107–125148. Cryer PE: Diverse causes of hypoglyce-mia-associated autonomic failure in dia-betes. N Engl J Med 350:2272–2279,2004149. Cryer PE, Davis SN, Shamoon H: Hypo-glycemia in diabetes. Diabetes Care 26:1902–1912, 2003150. Smith SA, Poland GA: Use of influenzaand pneumococcal vaccines in peoplewith diabetes. Diabetes Care 23:95–108,2000151. Colquhoun AJ, Nicholson KG, Botha JL,Raymond NT: Effectiveness of influenzavaccine in reducing hospital admissionsin people with diabetes. Epidemiol Infect119:335–341, 1997152. Bridges CB, Fukuda K, Uyeki TM, CoxNJ, Singleton JA: Prevention and controlof influenza: recommendations of theAdvisory Committee on ImmunizationPractices (ACIP). MMWR Recomm Rep51:1–31, 2002153. American Diabetes Association: Influ-enza and pneumococcal immunizationin diabetes (Position Statement). Diabe-tes Care 27 (Suppl. 1):S111–S113, 2004154. Gaede P, Lund-Andersen H, ParvingHH, Pedersen O: Effect of a multifacto-rial intervention on mortality in type 2diabetes. N Engl J Med 358:580–591,2008155. Arauz-Pacheco C, Parrott MA, Raskin P:The treatment of hypertension in adultpatients with diabetes. Diabetes Care 25:134–147, 2002156. Haffner SM: Management of dyslipide-mia in adults with diabetes. DiabetesCare 21:160–178, 1998157. Colwell JA: Aspirin therapy in diabetes.Diabetes Care 20:1767–1771, 1997158. Haire-Joshu D, Glasgow RE, Tibbs TL:Smoking and diabetes. Diabetes Care 22:1887–1898, 1999159. Buse JB, Ginsberg HN, Barkis GL, ClarkNG, Costa F, Eckel R, Fonseca V, Ger-stein HC, Grundy S, Nesto RW, PignoneMP, Plutzky J, Porte D, Redberg R, Stit-zel KF, Stone NJ: Primary prevention ofcardiovascular diseases in people withdiabetes mellitus: a scientific statementfrom the American Heart Associationand the American Diabetes Association.Diabetes Care 30:162–172, 2007160. Chobanian AV, Bakris GL, Black HR,Cushman WC, Green LA, Izzo JL Jr,Jones DW, Materson BJ, Oparil S,Wright JT Jr, Roccella EJ: The SeventhReport of the Joint National Committeeon Prevention, Detection, Evaluation,and Treatment of High Blood Pressure:the JNC 7 report. JAMA 289:2560–2572, 2003161. Bobrie G, Chatellier G, Genes N, ClersonP, Vaur L, Vaisse B, Menard J, MallionJM: Cardiovascular prognosis of“masked hypertension” detected byblood pressure self-measurement in el-derly treated hypertensive patients.JAMA 291:1342–1349, 2004162. Sega R, Facchetti R, Bombelli M, CesanaG, Corrao G, Grassi G, Mancia G: Prog-nostic value of ambulatory and homeblood pressures compared with officeblood pressure in the general popula-tion: follow-up results from the Pres-sioni Arteriose Monitorate e LoroAssociazioni (PAMELA) study. Circula-tion 111:1777–1783, 2005163. Tight blood pressure control and risk ofmacrovascular and microvascular com-plications in type 2 diabetes: UKPDS 38:UK Prospective Diabetes Study Group.BMJ 317:703–713, 1998164. Hansson L, Zanchetti A, Carruthers SG,Dahlof B, Elmfeldt D, Julius S, Menard J,Rahn KH, Wedel H, Westerling S: Ef-fects of intensive blood-pressure lower-ing and low-dose aspirin in patients withhypertension: principal results of theHypertension Optimal Treatment(HOT) randomised trial: HOT StudyGroup. Lancet 351:1755–1762, 1998165. Adler AI, Stratton IM, Neil HA, YudkinJS, Matthews DR, Cull CA, Wright AD,Turner RC, Holman RR: Association ofsystolic blood pressure with macrovas-cular and microvascular complicationsof type 2 diabetes (UKPDS 36): prospec-tive observational study. BMJ 321:412–419, 2000166. Lewington S, Clarke R, Qizilbash N,Peto R, Collins R: Age-specific relevanceof usual blood pressure to vascular mor-tality: a meta-analysis of individual datafor one million adults in 61 prospectivestudies. Lancet 360:1903–1913, 2002167. Stamler J, Vaccaro O, Neaton JD, Went-worth D: Diabetes, other risk factors,and 12-yr cardiovascular mortality formen screened in the Multiple Risk Fac-tor Intervention Trial. Diabetes Care 16:434–444, 1993168. Sacks FM, Svetkey LP, Vollmer WM, Ap-pel LJ, Bray GA, Harsha D, Obarzanek E,Conlin PR, Miller ER III, Simons-MortonDG, Karanja N, Lin PH: Effects on bloodpressure of reduced dietary sodium andthe Dietary Approaches to Stop Hyper-tension (DASH) diet: DASH-SodiumCollaborative Research Group. N EnglJ Med 344:3–10, 2001169. Tatti P, Pahor M, Byington RP, Di MauroP, Guarisco R, Strollo G, Strollo F: Out-come results of the Fosinopril VersusAmlodipine Cardiovascular Events Ran-domized Trial (FACET) in patients withhypertension and NIDDM. DiabetesCare 21:597–603, 1998170. Estacio RO, Jeffers BW, Hiatt WR, Big-gerstaff SL, Gifford N, Schrier RW: Theeffect of nisoldipine as compared withenalapril on cardiovascular outcomes inpatients with non-insulin-dependent di-abetes and hypertension. N Engl J Med338:645–652, 1998171. Schrier RW, Estacio RO, Mehler PS, Hi-att WR: Appropriate blood pressurecontrol in hypertensive and normoten-sive type 2 diabetes mellitus: a summaryof the ABCD trial. Nat Clin Pract Nephrol3:428–438, 2007172. Major outcomes in high-risk hyperten-sive patients randomized to angiotensin-converting enzyme inhibitor or calciumchannel blocker vs diuretic: the Antihy-pertensive and Lipid-Lowering Treat-ment to Prevent Heart Attack Trial(ALLHAT). JAMA 288:2981–2997,2002173. Psaty BM, Lumley T, Furberg CD, Schel-lenbaum G, Pahor M, Alderman MH,Weiss NS: Health outcomes associatedwith various antihypertensive therapiesused as first-line agents: a network meta-analysis. JAMA 289:2534–2544, 2003174. Effects of ramipril on cardiovascular andmicrovascular outcomes in people withdiabetes mellitus: results of the HOPEstudy and MICRO-HOPE substudy:Heart Outcomes Prevention EvaluationStudy Investigators. Lancet 355:253–259, 2000175. Pfeffer MA, Swedberg K, Granger CB,Held P, McMurray JJ, Michelson EL,Olofsson B, Ostergren J, Yusuf S, PocockS: Effects of candesartan on mortalityand morbidity in patients with chronicheart failure: the CHARM-Overall pro-gramme. Lancet 362:759–766, 2003176. Granger CB, McMurray JJ, Yusuf S, HeldP, Michelson EL, Olofsson B, OstergrenJ, Pfeffer MA, Swedberg K: Effects of can-Standards of Medical CareS54 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 43. desartan in patients with chronic heartfailure and reduced left-ventricular sys-tolic function intolerant to angiotensin-converting-enzyme inhibitors: theCHARM- Alternative trial. Lancet 362:772–776,2003177. McMurray JJ, Ostergren J, Swedberg K,Granger CB, Held P, Michelson EL,Olofsson B, Yusuf S, Pfeffer MA: Effectsof candesartan in patients with chronicheart failure and reduced left-ventricularsystolic function taking angiotensin-converting-enzyme inhibitors: theCHARM-Added trial. Lancet 362:767–771, 2003178. Lindholm LH, Ibsen H, Dahlof B, De-vereux RB, Beevers G, de Faire U, Fyhr-quist F, Julius S, Kjeldsen SE,Kristiansson K, Lederballe-Pedersen O,Nieminen MS, Omvik P, Oparil S,Wedel H, Aurup P, Edelman J, SnapinnS: Cardiovascular morbidity and mortal-ity in patients with diabetes in the Losar-tan Intervention For Endpoint reductionin hypertension study (LIFE): a random-ised trial against atenolol. Lancet 359:1004–1010, 2002179. Berl T, Hunsicker LG, Lewis JB, PfefferMA, Porush JG, Rouleau JL, Drury PL,Esmatjes E, Hricik D, Parikh CR, Raz I,Vanhille P, Wiegmann TB, Wolfe BM,Locatelli F, Goldhaber SZ, Lewis EJ: Car-diovascular outcomes in the IrbesartanDiabetic Nephropathy Trial of patientswith type 2 diabetes and overt nephrop-athy. Ann Intern Med 138:542–549,2003180. Laffel LM, McGill JB, Gans DJ: The ben-eficial effect of angiotensin-convertingenzyme inhibition with captopril on di-abetic nephropathy in normotensiveIDDM patients with microalbuminuria:North American MicroalbuminuriaStudy Group. Am J Med 99:497–504,1995181. Bakris GL, Williams M, Dworkin L, El-liott WJ, Epstein M, Toto R, Tuttle K,Douglas J, Hsueh W, Sowers J: Preserv-ing renal function in adults with hyper-tension and diabetes: a consensusapproach: National Kidney FoundationHypertension and Diabetes ExecutiveCommittees Working Group. AmJ Kid-ney Dis 36:646–661, 2000182. PsatyBM,SmithNL,SiscovickDS,Koep-sell TD, Weiss NS, Heckbert SR, Lemai-tre RN, Wagner EH, Furberg CD: Healthoutcomes associated with antihyperten-sive therapies used as first-line agents: asystematic review and meta-analysis.JAMA 277:739–745, 1997183. Patel A, MacMahon S, Chalmers J, NealB, Woodward M, Billot L, Harrap S,Poulter N, Marre M, Cooper M, GlasziouP, Grobbee DE, Hamet P, Heller S, LiuLS, Mancia G, Mogensen CE, Pan CY,Rodgers A, Williams B: Effects of a fixedcombination of perindopril and indap-amide on macrovascular and microvas-cular outcomes in patients with type 2diabetes mellitus (the ADVANCE trial):a randomised controlled trial. Lancet370:829–840, 2007184. Sibai BM: Treatment of hypertension inpregnant women. N Engl J Med 335:257–265, 1996185. Baigent C, Keech A, Kearney PM, Black-well L, Buck G, Pollicino C, Kirby A,Sourjina T, Peto R, Collins R, Simes R:Efficacy and safety of cholesterol-lower-ing treatment: prospective meta-analysisof data from 90,056 participants in 14randomised trials of statins. Lancet 366:1267–1278, 2005186. Pyorala K, Pedersen TR, Kjekshus J,Faergeman O, Olsson AG, ThorgeirssonG: Cholesterol lowering with simvasta-tin improves prognosis of diabetic pa-tients with coronary heart disease: asubgroup analysis of the ScandinavianSimvastatin Survival Study (4S). Diabe-tes Care 20:614–620, 1997187. Heart Protection Study CollaborativeGroup: MRC/BHF Heart ProtectionStudy of cholesterol-lowering with sim-vastatin in 5963 people with diabetes: arandomised placebo-controlled trial.Lancet 361:2005–2016, 2003188. Goldberg RB, Mellies MJ, Sacks FM,Moye LA, Howard BV, Howard WJ,Davis BR, Cole TG, Pfeffer MA, Braun-wald E: Cardiovascular events and theirreduction with pravastatin in diabeticand glucose-intolerant myocardial in-farction survivors with average choles-terol levels: subgroup analyses in thecholesterol and recurrent events (CARE)trial: the Care Investigators. Circulation98:2513–2519, 1998189. Shepherd J, Barter P, Carmena R, Deed-wania P, Fruchart JC, Haffner S, Hsia J,Breazna A, LaRosa J, Grundy S, WatersD: Effect of lowering LDL cholesterolsubstantially below currently recom-mended levels in patients with coronaryheart disease and diabetes: the Treatingto New Targets (TNT) study. DiabetesCare 29:1220–1226, 2006190. Sever PS, Poulter NR, Dahlof B, WedelH, Collins R, Beevers G, Caulfield M,Kjeldsen SE, Kristinsson A, McInnes GT,Mehlsen J, Nieminen M, O’Brien E, Os-tergren J: Reduction in cardiovascularevents with atorvastatin in 2,532 pa-tients with type 2 diabetes: Anglo-Scan-dinavian Cardiac Outcomes Trial–Lipid-Lowering Arm (ASCOT-LLA).Diabetes Care 28:1151–1157, 2005191. Knopp RH, d’Emden M, Smilde JG, Po-cock SJ: Efficacy and safety of atorvasta-tin in the prevention of cardiovascularend points in subjects with type 2 diabe-tes: the Atorvastatin Study for Preven-tion of Coronary Heart DiseaseEndpoints in Non-insulin-dependentdiabetes mellitus (ASPEN). DiabetesCare 29:1478–1485, 2006192. Singh IM, Shishehbor MH, Ansell BJ:High-density lipoprotein as a therapeu-tic target: a systematic review. JAMA298:786–798, 2007193. Singh IM, Shishehbor MH, Ansell BJ:High-density lipoprotein as a therapeu-tic target: a systematic review. JAMA298:786–798, 2007194. Canner PL, Berge KG, Wenger NK,Stamler J, Friedman L, Prineas RJ,Friedewald W: Fifteen year mortality inCoronary Drug Project patients: long-term benefit with niacin. J Am Coll Car-diol 8:1245–1255, 1986195. Rubins HB, Robins SJ, Collins D, Fye CL,Anderson JW, Elam MB, Faas FH, Lin-ares E, Schaefer EJ, Schectman G, WiltTJ, Wittes J: Gemfibrozil for the second-ary prevention of coronary heart diseasein men with low levels of high-densitylipoprotein cholesterol: Veterans AffairsHigh-Density Lipoprotein CholesterolIntervention Trial Study Group. N EnglJ Med 341:410–418, 1999196. Frick MH, Elo O, Haapa K, HeinonenOP, Heinsalmi P, Helo P, Huttunen JK,Kaitaniemi P, Koskinen P, Manninen V:Helsinki Heart Study: primary-preven-tion trial with gemfibrozil in middle-aged men with dyslipidemia: safety oftreatment, changes in risk factors, andincidence of coronary heart disease.N Engl J Med 317:1237–1245, 1987197. Keech A, Simes RJ, Barter P, Best J, ScottR, Taskinen MR, Forder P, Pillai A, DavisT, Glasziou P, Drury P, Kesaniemi YA,Sullivan D, Hunt D, Colman P, d’EmdenM, Whiting M, Ehnholm C, Laakso M:Effects of long-term fenofibrate therapyon cardiovascular events in 9795 peoplewith type 2 diabetes mellitus (the FIELDstudy): randomised controlled trial. Lan-cet 366:1849–1861, 2005198. Executive Summary of The Third Reportof The National Cholesterol EducationProgram (NCEP) Expert Panel on Detec-tion, Evaluation, And Treatment of HighBlood Cholesterol In Adults (AdultTreatment Panel III). JAMA 285:2486–2497, 2001199. Hayward RA, Hofer TP, Vijan S: Narra-tive review: lack of evidence for recom-mended low-density lipoproteintreatment targets: a solvable problem.Ann Intern Med 145:520–530, 2006200. Cannon CP, Braunwald E, McCabe CH,Rader DJ, Rouleau JL, Belder R, Joyal SV,Hill KA, Pfeffer MA, Skene AM: Inten-sive versus moderate lipid lowering withstatins after acute coronary syndromes.N Engl J Med 350:1495–1504, 2004201. de Lemos JA, Blazing MA, Wiviott SD,Lewis EF, Fox KA, White HD, RouleauJL, Pedersen TR, Gardner LH, Mukher-jee R, Ramsey KE, Palmisano J, Bilhei-mer DW, Pfeffer MA, Califf RM,Braunwald E: Early intensive vs a de-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S55
  • 44. layed conservative simvastatin strategyin patients with acute coronary syn-dromes: phase Z of the A to Z trial. JAMA292:1307–1316, 2004202. Nissen SE, Tuzcu EM, Schoenhagen P,Brown BG, Ganz P, Vogel RA, Crowe T,Howard G, Cooper CJ, Brodie B, GrinesCL, DeMaria AN: Effect of intensivecompared with moderate lipid-loweringtherapy on progression of coronary ath-erosclerosis: a randomized controlledtrial. JAMA 291:1071–1080, 2004203. Grundy SM, Cleeman JI, Merz CN,Brewer HB Jr, Clark LT, HunninghakeDB, Pasternak RC, Smith SC Jr, StoneNJ: Implications of recent clinical trialsfor the National Cholesterol EducationProgram Adult Treatment Panel IIIguidelines. Circulation 110:227–239,2004204. Chasman DI, Posada D, SubrahmanyanL, Cook NR, Stanton VP Jr, Ridker PM:Pharmacogenetic study of statin therapyand cholesterol reduction. JAMA291:2821–2827, 2004205. Elam MB, Hunninghake DB, Davis KB,Garg R, Johnson C, Egan D, Kostis JB,Sheps DS, Brinton EA: Effect of niacin onlipid and lipoprotein levels and glycemiccontrol in patients with diabetes and pe-ripheral arterial disease: the ADMITstudy: a randomized trial: Arterial Dis-ease Multiple Intervention Trial. JAMA284:1263–1270, 2000206. Grundy SM, Vega GL, McGovern ME,Tulloch BR, Kendall DM, Fitz-Patrick D,Ganda OP, Rosenson RS, Buse JB, Rob-ertson DD, Sheehan JP: Efficacy, safety,and tolerability of once-daily niacin forthe treatment of dyslipidemia associatedwith type 2 diabetes: results of the as-sessment of diabetes control and evalu-ation of the efficacy of niaspan trial. ArchIntern Med 162:1568–1576, 2002207. Jones PH, and Davidson MH Reportingrate of rhabdomyolysis with fenofibrateϩ statin versus gemfibrozil ϩ any statin.Am J Cardiol 95:120–122, 2005208. Brunzell JD, Davidson M, Furberg CD,GoldbergRB,HowardBV,SteinJH,Witz-tum JL: Lipoprotein management in pa-tients with cardiometabolic risk:consensus statement from the AmericanDiabetes Association and the AmericanCollege of Cardiology Foundation. Dia-betes Care 31:811–822, 2008209. Colhoun HM, Betteridge DJ, DurringtonPN, Hitman GA, Neil HA, LivingstoneSJ, Thomason MJ, Mackness MI, Charl-ton-Menys V, Fuller JH: Primary preven-tion of cardiovascular disease withatorvastatin in type 2 diabetes in the Col-laborative Atorvastatin Diabetes Study(CARDS): multicentre randomised pla-cebo-controlled trial. Lancet 364:685–696, 2004210. American Diabetes Association: Aspirintherapy in diabetes (Position Statement).Diabetes Care 27 (Suppl. 1):S72–S73,2004211. Hayden M, Pignone M, Phillips C, Mul-row C: Aspirin for the primary preven-tion of cardiovascular events: a summaryof the evidence for the U.S. PreventiveServices Task Force. Ann Intern Med 136:161–172, 2002212. US Preventive Services Task Force: As-pirin for the primary prevention of car-diovascular events: recommendationand rationale. Ann Intern Med 136:157–160, 2002213. Antithrombotic Trialists Collaboration:Collaborative meta-analysis of random-ised trials of antiplatelet therapy for pre-vention of death, myocardial infarction,and stroke in high risk patients. BMJ324:71–86, 2002214. Smith SC Jr, Allen J, Blair SN, BonowRO, Brass LM, Fonarow GC, GrundySM, Hiratzka L, Jones D, Krumholz HM,Mosca L, Pasternak RC, Pearson T, Pfef-fer MA, Taubert KA: AHA/ACC guide-lines for secondary prevention forpatients with coronary and other athero-sclerotic vascular disease: 2006 update:endorsed by the National Heart, Lung,and Blood Institute. Circulation 113:2363–2372, 2006215. Campbell CL, Smyth S, Montalescot G,Steinhubl SR: Aspirin dose for the pre-vention of cardiovascular disease: a sys-tematic review. JAMA 297:2018–2024,2007216. Sacco M, Pellegrini F, Roncaglioni MC,Avanzini F, Tognoni G, Nicolucci A: Pri-mary prevention of cardiovascularevents with low-dose aspirin and vita-min E in type 2 diabetic patients: resultsof the Primary Prevention Project (PPP)trial. Diabetes Care 26:3264–3272,2003217. Bhatt DL, Marso SP, Hirsch AT, RinglebPA, Hacke W, Topol EJ: Amplified ben-efit of clopidogrel versus aspirin in pa-tients with diabetes mellitus. Am JCardiol 90:625–628, 2002218. American Diabetes Asociation: Smokingand diabetes (Position Statement). Dia-betes Care 27 (Suppl. 1):S74–S75, 2004219. US Preventive Services Task Force:Counseling to prevent tobacco use andtobacco-related diseases: recommenda-tion statement. Rockville, MD, Agencyfor Healthcare Research and Quality,2003220. Ranney L, Melvin C, Lux L, McClain E,Lohr KN: Systematic review: smokingcessation intervention strategies foradults and adults in special populations.Ann Intern Med 145:845–856, 2006221. Scognamiglio R, Negut C, Ramondo A,Tiengo A, Avogaro A: Detection of coro-nary artery disease in asymptomatic pa-tients with type 2 diabetes mellitus. J AmColl Cardiol 47:65–71, 2006222. Boden WE, O’Rourke RA, Teo KK, Har-tigan PM, Maron DJ, Kostuk WJ, Knudt-son M, Dada M, Casperson P, Harris CL,Chaitman BR, Shaw L, Gosselin G,Nawaz S, Title LM, Gau G, Blaustein AS,Booth DC, Bates ER, Spertus JA, BermanDS, Mancini GB, Weintraub WS: Opti-mal medical therapy with or without PCIfor stable coronary disease. N Engl J Med356:1503–1516, 2007223. Wackers FJ, Chyun DA, Young LH,Heller GV, Iskandrian AE, Davey JA,Barrett EJ, Taillefer R, Wittlin SD, Filip-chuk N, Ratner RE, Inzucchi SE: Reso-lution of asymptomatic myocardialischemia in patients with type 2 diabetesin the Detection of Ischemia in Asymp-tomatic Diabetics (DIAD) study. Diabe-tes Care 30:2892–2898, 2007224. Braunwald E, Domanski MJ, Fowler SE,Geller NL, Gersh BJ, Hsia J, Pfeffer MA,Rice MM, Rosenberg YD, Rouleau JL:Angiotensin-converting-enzyme inhibi-tion in stable coronary artery disease.N Engl J Med 351:2058–2068, 2004225. Effects of the angiotensin-receptorblocker telmisartan on cardiovascularevents in high-risk patients intolerant toangiotensin-converting enzyme inhibi-tors: a randomised controlled trial. Lan-cet 372:1174–1183, 2008226. Garg JP, Bakris GL: Microalbuminuria:marker of vascular dysfunction, risk fac-tor for cardiovascular disease. Vasc Med7:35–43, 2002227. Klausen K, Borch-Johnsen K, Feldt-Ras-mussen B, Jensen G, Clausen P,Scharling H, Appleyard M, Jensen JS:Very low levels of microalbuminuria areassociated with increased risk of coro-nary heart disease and death indepen-dently of renal function, hypertension,and diabetes. Circulation 110:32–35,2004228. Gall MA, Hougaard P, Borch-Johnsen K,Parving HH: Risk factors for develop-ment of incipient and overt diabetic ne-phropathy in patients with non-insulindependent diabetes mellitus: prospec-tive, observational study. BMJ 314:783–788, 1997229. Ravid M, Lang R, Rachmani R, LishnerM: Long-term renoprotective effect ofangiotensin-converting enzyme inhibi-tion in non-insulin-dependent diabetesmellitus: a 7-year follow-up study. ArchIntern Med 156:286–289, 1996230. Reichard P, Nilsson BY, Rosenqvist U:The effect of long-term intensified insu-lin treatment on the development of mi-crovascular complications of diabetesmellitus. N Engl J Med 329:304–309,1993231. Effect of intensive therapy on the devel-opment and progression of diabeticnephropathy in the Diabetes Controland Complications Trial: the DiabetesControl and Complications (DCCT)Research Group. Kidney Int 47:1703–Standards of Medical CareS56 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 45. 1720, 1995232. Lewis EJ, Hunsicker LG, Bain RP, RohdeRD: The effect of angiotensin-convert-ing-enzyme inhibition on diabetic ne-phropathy: the Collaborative StudyGroup. N Engl J Med 329:1456–1462,1993233. Remuzzi G, Macia M, Ruggenenti P: Pre-vention and treatment of diabetic renaldisease in type 2 diabetes: the BENE-DICT study. J Am Soc Nephrol 17:S90–S97, 2006234. Lewis EJ, Hunsicker LG, Clarke WR,Berl T, Pohl MA, Lewis JB, Ritz E, AtkinsRC, Rohde R, Raz I: Renoprotective ef-fect of the angiotensin-receptor antago-nist irbesartan in patients withnephropathy due to type 2 diabetes.N Engl J Med 345:851–860, 2001235. Brenner BM, Cooper ME, de Zeeuw D,Keane WF, Mitch WE, Parving HH, Re-muzzi G, Snapinn SM, Zhang Z, Shahin-far S: Effects of losartan on renal andcardiovascular outcomes in patientswith type 2 diabetes and nephropathy.N Engl J Med 345:861–869, 2001236. Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S,Arner P: The effect of irbesartan on thedevelopment of diabetic nephropathy inpatients with type 2 diabetes. N EnglJ Med 345:870–878, 2001237. Pepine CJ, Handberg EM, Cooper-De-Hoff RM, Marks RG, Kowey P, MesserliFH, Mancia G, Cangiano JL, Garcia-Bar-reto D, Keltai M, Erdine S, Bristol HA,Kolb HR, Bakris GL, Cohen JD, ParmleyWW: A calcium antagonist vs a non-cal-cium antagonist hypertension treatmentstrategy for patients with coronary arterydisease: the International Verapamil-Trandolapril study (INVEST): a ran-domized controlled trial. JAMA290:2805–2816, 2003238. Bakris GL, Siomos M, Richardson D,Janssen I, Bolton WK, Hebert L, AgarwalR, Catanzaro D: ACE inhibition or an-giotensin receptor blockade: impact onpotassium in renal failure: VAL-K StudyGroup. Kidney Int 58:2084–2092, 2000239. Mogensen CE, Neldam S, Tikkanen I,Oren S, Viskoper R, Watts RW, CooperME: Randomised controlled trial of dualblockade of renin-angiotensin system inpatients with hypertension, microalbu-minuria, and non-insulin dependent di-abetes: the candesartan and lisinoprilmicroalbuminuria (CALM) study. BMJ321:1440–1444, 2000240. Schjoedt KJ, Jacobsen P, Rossing K,Boomsma F, Parving HH: Dual blockadeof the renin-angiotensin-aldosteronesystem in diabetic nephropathy: the roleof aldosterone. Horm Metab Res 37(Suppl. 1):4–8, 2005241. Schjoedt KJ, Rossing K, Juhl TR,Boomsma F, Rossing P, Tarnow L, Parv-ing HH: Beneficial impact of spironolac-tone in diabetic nephropathy. Kidney Int68:2829–2836, 2005242. Parving HH, Persson F, Lewis JB, LewisEJ, Hollenberg NK: Aliskiren combinedwith losartan in type 2 diabetes and ne-phropathy. N Engl J Med 358:2433–2446, 2008243. Pijls LT, de Vries H, Donker AJ, van EijkJT: The effect of protein restriction onalbuminuria in patients with type 2 dia-betes mellitus: a randomized trial. Neph-rol Dial Transplant 14:1445–1453, 1999244. Pedrini MT, Levey AS, Lau J, ChalmersTC, Wang PH: The effect of dietary pro-tein restriction on the progression of di-abetic and nondiabetic renal diseases: ameta-analysis. Ann Intern Med 124:627–632, 1996245. Hansen HP, Tauber-Lassen E, JensenBR, Parving HH: Effect of dietary proteinrestriction on prognosis in patients withdiabetic nephropathy. Kidney Int62:220–228, 2002246. Kasiske BL, Lakatua JD, Ma JZ, Louis TA:A meta-analysis of the effects of dietaryprotein restriction on the rate of declinein renal function. Am J Kidney Dis 31:954–961, 1998247. Eknoyan G, Hostetter T, Bakris GL, He-bert L, Levey AS, Parving HH, SteffesMW, Toto R: Proteinuria and othermarkers of chronic kidney disease: a po-sition statement of the national kidneyfoundation (NKF) and the national insti-tute of diabetes and digestive and kidneydiseases (NIDDK). Am J Kidney Dis 42:617–622, 2003248. Levey AS, Coresh J, Balk E, Kausz AT,Levin A, Steffes MW, Hogg RJ, PerroneRD, Lau J, Eknoyan G: National KidneyFoundation practice guidelines forchronic kidney disease: evaluation, clas-sification, and stratification. Ann InternMed 139:137–147, 2003249. Kramer H, Molitch ME: Screening forkidney disease in adults with diabetes.Diabetes Care 28:1813–1816, 2005250. Kramer HJ, Nguyen QD, Curhan G, HsuCY: Renal insufficiency in the absence ofalbuminuria and retinopathy amongadults with type 2 diabetes mellitus.JAMA 289:3273–3277, 2003251. Tsalamandris C, Allen TJ, Gilbert RE,Sinha A, Panagiotopoulos S, Cooper ME,Jerums G: Progressive decline in renalfunction in diabetic patients with andwithout albuminuria. Diabetes 43:649–655, 1994252. Levey AS, Bosch JP, Lewis JB, Greene T,Rogers N, Roth D: A more accuratemethod to estimate glomerular filtrationrate from serum creatinine: a new pre-diction equation: Modification of Diet inRenal Disease Study Group. Ann InternMed 130:461–470, 1999253. Levinsky NG: Specialist evaluation inchronic kidney disease: too little, toolate. Ann Intern Med 137:542–543, 2002254. American Diabetes Association: Ne-phropathy in diabetes (Position State-ment). Diabetes Care 27 (Suppl. 1):S79–S83, 2004255. Klein R: Hyperglycemia and microvas-cular and macrovascular disease in dia-betes. Diabetes Care 18:258–268, 1995256. Estacio RO, McFarling E, Biggerstaff S,Jeffers BW, Johnson D, Schrier RW:Overt albuminuria predicts diabetic ret-inopathy in Hispanics with NIDDM. AmJ Kidney Dis 31:947–953, 1998257. Leske MC, Wu SY, Hennis A, Hyman L,Nemesure B, Yang L, Schachat AP: Hy-perglycemia, blood pressure, and the9-year incidence of diabetic retinopathy:the Barbados Eye Studies. Ophthalmology112:799–805, 2005258. Fong DS, Aiello LP, Ferris FL III, Klein R:Diabetic retinopathy. Diabetes Care 27:2540–2553, 2004259. DCCT: Effect of pregnancy on microvas-cular complications in the diabetes con-trol and complications trial: TheDiabetes Control and ComplicationsTrial Research Group. Diabetes Care 23:1084–1091, 2000260. The Diabetic Retinopathy Study (DRS)Research Group: Preliminary report onthe effects of photocoagulation therapy:DRS Report #1. Am J Ophthalmol 81:383–396, 1976261. Photocoagulation for diabetic macularedema: Early Treatment Diabetic Reti-nopathy Study report number 1: EarlyTreatment Diabetic Retinopathy StudyResearch Group. Arch Ophthalmol 103:1796–1806, 1985262. Klein R, Klein BE, Moss SE, Davis MD,DeMets DL: The Wisconsin epidemio-logic study of diabetic retinopathy. II.Prevalence and risk of diabetic retinop-athy when age at diagnosis is less than 30years. Arch Ophthalmol 102:520–526,1984263. Harris MI, Klein R, Welborn TA,Knuiman MW: Onset of NIDDM occursat least 4–7 yr before clinical diagnosis.Diabetes Care 15:815–819, 1992264. Vijan S, Hofer TP, Hayward RA: Cost-utility analysis of screening intervals fordiabetic retinopathy in patients withtype 2 diabetes mellitus. JAMA283:889–896, 2000265. Klein R: Screening interval for retinopa-thy in type 2 diabetes. Lancet 361:190–191, 2003266. Younis N, Broadbent DM, Vora JP, Har-ding SP: Incidence of sight-threateningretinopathy in patients with type 2 dia-betes in the Liverpool Diabetic EyeStudy: a cohort study. Lancet 361:195–200, 2003267. Ahmed J, Ward TP, Bursell SE, AielloLM, Cavallerano JD, Vigersky RA: Thesensitivity and specificity of nonmydri-atic digital stereoscopic retinal imagingin detecting diabetic retinopathy. Diabe-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S57
  • 46. tes Care 29:2205–2209, 2006268. American Diabetes Association: Reti-nopathy in diabetes. Diabetes Care 27(Suppl. 1):S84–S87, 2004269. Ciulla TA, Amador AG, Zinman B: Dia-betic retinopathy and diabetic macularedema: pathophysiology, screening, andnovel therapies. Diabetes Care 26:2653–2664, 2003270. Boulton AJ, Vinik AI, Arezzo JC, Bril V,Feldman EL, Freeman R, Malik RA, Ma-ser RE, Sosenko JM, Ziegler D: Diabeticneuropathies: a statement by the Amer-ican Diabetes Association. Diabetes Care28:956–962, 2005271. Vinik AI, Maser RE, Mitchell BD, Free-man R: Diabetic autonomic neuropathy.Diabetes Care 26:1553–1579, 2003272. Boulton AJ, Armstrong DG, Albert SF,Frykberg RG, Hellman R, Kirkman MS,Lavery LA, Lemaster JW, Mills JL Sr,Mueller MJ, Sheehan P, Wukich DK:Comprehensive foot examination andrisk assessment: a report of the task forceof the foot care interest group of theAmerican Diabetes Association, with en-dorsement by the American Associationof Clinical Endocrinologists. DiabetesCare 31:1679–1685, 2008273. American Diabetes Association: Periph-eral arterial disease in people with dia-betes (Consensus Statement). DiabetesCare 26:3333–3341, 2003274. American Diabetes Association: Consen-sus Development Conference on Dia-betic Foot Wound Care: 7–8 April1999, Boston, Massachusetts. DiabetesCare 22:1354–1360, 1999275. Silverstein J, Klingensmith G, CopelandKC, Plotnick L, Kaufman F, Laffel L,Deeb LC, Grey M, Anderson BJ, Hol-zmeister LA, Clark NG: Care of childrenand adolescents with type 1 diabetesmellitus: a statement of the AmericanDiabetes Association. Diabetes Care 28:186–212, 2005276. Northam EA, Anderson PJ, Werther GA,Warne GL, Adler RG, Andrewes D: Neu-ropsychological complications of IDDMin children 2 years after disease onset.Diabetes Care 21:379–384, 1998277. Rovet J, Alvarez M: Attentional function-ing in children and adolescents withIDDM. Diabetes Care 20:803–810, 1997278. Bjorgaas M, Gimse R, Vik T, Sand T:Cognitive function in type 1 diabeticchildren with and without episodes ofsevere hypoglycaemia. Acta Paediatr 86:148–153, 1997279. Doyle EA, Weinzimer SA, Steffen AT,Ahern JA, Vincent M, Tamborlane WV:A randomized, prospective trial compar-ing the efficacy of continuous subcuta-neous insulin infusion with multipledaily injections using insulin glargine.Diabetes Care 27:1554–1558, 2004280. Nimri R, Weintrob N, Benzaquen H,Ofan R, Fayman G, Phillip M: Insulinpump therapy in youth with type 1 dia-betes: a retrospective paired study. Pedi-atrics 117:2126–2131, 2006281. Krantz JS, Mack WJ, Hodis HN, Liu CR,Liu CH, Kaufman FR: Early onset of sub-clinical atherosclerosis in young personswith type 1 diabetes. J Pediatr 145:452–457, 2004282. Jarvisalo MJ, Putto-Laurila A, Jartti L,Lehtimaki T, Solakivi T, Ronnemaa T,Raitakari OT: Carotid artery intima-me-dia thickness in children with type 1 di-abetes. Diabetes 51:493–498, 2002283. Haller MJ, Samyn M, Nichols WW,Brusko T, Wasserfall C, Schwartz RF, At-kinson M, Shuster JJ, Pierce GL, Silver-stein JH: Radial artery tonometrydemonstrates arterial stiffness in chil-dren with type 1 diabetes. Diabetes Care27:2911–2917, 2004284. Orchard TJ, Forrest KY, Kuller LH,Becker DJ: Lipid and blood pressuretreatment goals for type 1 diabetes: 10-year incidence data from the PittsburghEpidemiology of Diabetes Complica-tions Study. Diabetes Care 24:1053–1059, 2001285. Kavey RE, Allada V, Daniels SR, HaymanLL, McCrindle BW, Newburger JW,Parekh RS, Steinberger J: Cardiovascularrisk reduction in high-risk pediatric pa-tients: a scientific statement from theAmerican Heart Association ExpertPanel on Population and Prevention Sci-ence; the Councils on CardiovascularDisease in the Young, Epidemiology andPrevention, Nutrition, Physical Activityand Metabolism, High Blood PressureResearch, Cardiovascular Nursing, andthe Kidney in Heart Disease; and the In-terdisciplinary Working Group onQuality of Care and Outcomes Research:endorsed by the American Academy ofPediatrics. Circulation 114:2710–2738,2006286. McCrindle BW, Urbina EM, DennisonBA, Jacobson MS, Steinberger J, Roc-chini AP, Hayman LL, Daniels SR: Drugtherapy of high-risk lipid abnormalitiesin children and adolescents: a scientificstatement from the American Heart As-sociation Atherosclerosis, Hypertension,and Obesity in Youth Committee, Coun-cil of Cardiovascular Disease in theYoung, with the Council on Cardiovas-cular Nursing. Circulation 115:1948–1967, 2007287. Salo P, Viikari J, Hamalainen M, Lapin-leimu H, Routi T, Ronnemaa T, Sep-panen R, Jokinen E, Valimaki I, SimellO: Serum cholesterol ester fatty acids in7- and 13-month-old children in a pro-spective randomized trial of a low-satu-rated fat, low-cholesterol diet: the STRIPbaby project: Special Turku coronaryRisk factor Intervention Project for chil-dren. Acta Paediatr 88:505–512, 1999288. Efficacy and safety of lowering dietaryintake of fat and cholesterol in childrenwith elevated low-density lipoproteincholesterol: the Dietary InterventionStudy in Children (DISC): the WritingGroup for the DISC Collaborative Re-search Group. JAMA 273:1429–1435,1995289. McCrindle BW, Ose L, Marais AD: Effi-cacy and safety of atorvastatin in chil-dren and adolescents with familialhypercholesterolemia or severe hyper-lipidemia: a multicenter, randomized,placebo-controlled trial. J Pediatr143:74–80, 2003290. de Jongh S, Lilien MR, op’t RJ, Stroes ES,Bakker HD, Kastelein JJ: Early statintherapy restores endothelial function inchildren with familial hypercholesterol-emia. J Am Coll Cardiol 40:2117–2121,2002291. Wiegman A, Hutten BA, de Groot E,Rodenburg J, Bakker HD, Buller HR,Sijbrands EJ, Kastelein JJ: Efficacy andsafety of statin therapy in children withfamilial hypercholesterolemia: arandomized controlled trial. JAMA 292:331–337, 2004292. Holmes GK: Screening for coeliac dis-ease in type 1 diabetes. Arch Dis Child87:495–498, 2002293. Rewers M, Liu E, Simmons J, RedondoMJ, Hoffenberg EJ: Celiac disease asso-ciated with type 1 diabetes mellitus.Endocrinol Metab Clin North Am 33:197–214, 2004294. Roldan MB, Alonso M, Barrio R: Thyroidautoimmunity in children and adoles-cents with type 1 diabetes mellitus. Dia-betes Nutr Metab 12:27–31, 1999295. Kordonouri O, Deiss D, Danne T,Dorow A, Bassir C, Gruters-Kieslich A:Predictivity of thyroid autoantibodiesfor the development of thyroid disordersin children and adolescents with type 1diabetes. Diabet Med 19:518–521, 2002296. Mohn A, Di Michele S, Di Luzio R,Tumini S, Chiarelli F: The effect of sub-clinical hypothyroidism on metaboliccontrol in children and adolescents withtype 1 diabetes mellitus. Diabet Med 19:70–73, 2002297. Chase HP, Garg SK, Cockerham RS,Wilcox WD, Walravens PA: Thyroidhormone replacement and growth ofchildren with subclinical hypothyroid-ism and diabetes. Diabet Med7:299–303, 1990298. Eppens MC, Craig ME, Cusumano J,Hing S, Chan AK, Howard NJ, Silink M,Donaghue KC: Prevalence of diabetescomplications in adolescents with type 2compared with type 1 diabetes. DiabetesCare 29:1300–1306, 2006299. Kitzmiller JL, Gavin LA, Gin GD, Jo-vanovic-Peterson L, Main EK, ZigrangWD: Preconception care of diabetes: gly-cemic control prevents congenitalanomalies. JAMA 265:731–736, 1991Standards of Medical CareS58 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 47. 300. Goldman JA, Dicker D, Feldberg D, Ye-shaya A, Samuel N, Karp M: Pregnancyoutcome in patients with insulin-depen-dent diabetes mellitus with preconcep-tional diabetic control: a comparativestudy. AmJ Obstet Gynecol 155:293–297,1986301. Rosenn B, Miodovnik M, Combs CA,Khoury J, Siddiqi TA: Pre-conceptionmanagement of insulin-dependent dia-betes: improvement of pregnancy out-come. Obstet Gynecol 77:846–849,1991302. Tchobroutsky C, Vray MM, Altman JJ:Risk/benefit ratio of changing late ob-stetrical strategies in the management ofinsulin-dependent diabetic pregnancies:a comparison between 1971–1977 and1978–1985 periods in 389 pregnancies.Diabete Metab 17:287–294, 1991303. Willhoite MB, Bennert HW Jr, PalomakiGE, Zaremba MM, Herman WH, Wil-liams JR, Spear NH: The impact of pre-conception counseling on pregnancyoutcomes: the experience of the MaineDiabetes in Pregnancy Program. DiabetesCare 16:450–455, 1993304. Cooper WO, Hernandez-Diaz S, Arbo-gast PG, Dudley JA, Dyer S, Gideon PS,Hall K, Ray WA: Major congenital mal-formations after first-trimester exposureto ACE inhibitors. N Engl J Med354:2443–2451, 2006305. Kitzmiller JL, Buchanan TA, Kjos S,Combs CA, Ratner RE: Pre-conceptioncare of diabetes, congenital malforma-tions, and spontaneous abortions. Dia-betes Care 19:514–541, 1996306. American Diabetes Association: Precon-ception care of women with diabetes(Position Statement). Diabetes Care 27(Suppl. 1):S76–S78, 2004307. Brown AF, Mangione CM, Saliba D,Sarkisian CA: Guidelines for improvingthe care of the older person with diabe-tes mellitus. J Am Geriatr Soc 51:S265–S280, 2003308. Curb JD, Pressel SL, Cutler JA, SavagePJ, Applegate WB, Black H, Camel G,Davis BR, Frost PH, Gonzalez N, GuthrieG, Oberman A, Rutan GH, Stamler J: Ef-fect of diuretic-based antihypertensivetreatment on cardiovascular disease riskin older diabetic patients with isolatedsystolic hypertension: Systolic Hyper-tension in the Elderly Program Cooper-ative Research Group. JAMA 276:1886–1892, 1996309. Beckett NS, Peters R, Fletcher AE, Staes-sen JA, Liu L, Dumitrascu D, Stoy-anovsky V, Antikainen RL, Nikitin Y,Anderson C, Belhani A, Forette F, Raj-kumar C, Thijs L, Banya W, Bulpitt CJ:Treatment of hypertension in patients80 years of age or older. N Engl J Med358:1887–1898, 2008310. Clement S, Braithwaite SS, Magee MF,Ahmann A, Smith EP, Schafer RG, HirshIB: Management of diabetes and hyper-glycemia in hospitals. Diabetes Care 27:553–591, 2004311. American Association of Clinical Endo-crinologists: Inpatient diabetes and met-abolic control: conference proceedings.Endocr Pract 10 (Suppl. 2):1–108, 2004312. Garber AJ, Moghissi ES, Bransome ED Jr,Clark NG, Clement S, Cobin RH, Fur-nary AP, Hirsch IB, Levy P, Roberts R,van den BG, Zamudio V: American Col-lege of Endocrinology position state-ment on inpatient diabetes andmetabolic control. EndocrPract 10(Suppl. 2):4–9, 2004313. ACE/ADA Task Force on Inpatient Dia-betes: American College of Endocrinol-ogy and American Diabetes AssociationConsensus statement on inpatient dia-betes and glycemic control: a call to ac-tion. Diabetes Care 29:1955–1962, 2006314. Centers for Disease Control and Preven-tion: Hospitalizations for Diabetes asAny-Listed Diagnosis. National DiabetesSurveillance System. Atlanta, Georgia,Centers for Disease Control and Preven-tion, 2003315. Pomposelli JJ, Baxter JK III, Babineau TJ,Pomfret EA, Driscoll DF, Forse RA,Bistrian BR: Early postoperative glucosecontrol predicts nosocomial infectionrate in diabetic patients. J Parenter En-teral Nutr 22:77–81, 1998316. Umpierrez GE, Isaacs SD, Bazargan N,You X, Thaler LM, Kitabchi AE: Hyper-glycemia: an independent marker of in-hospital mortality in patients withundiagnosed diabetes. J Clin EndocrinolMetab 87:978–982, 2002317. Capes SE, Hunt D, Malmberg K, Ger-stein HC: Stress hyperglycaemia and in-creased risk of death after myocardialinfarction in patients with and withoutdiabetes: a systematic overview. Lancet355:773–778, 2000318. Bolk J, van der PT, Cornel JH, ArnoldAE, Sepers J, Umans VA: Impaired glu-cose metabolism predicts mortality aftera myocardial infarction. Int J Cardiol 79:207–214, 2001319. Malmberg K: Prospective randomisedstudy of intensive insulin treatment onlong term survival after acute myocardialinfarction in patients with diabetes mel-litus: DIGAMI (Diabetes Mellitus, Insu-lin Glucose Infusion in AcuteMyocardial Infarction) Study Group.BMJ 314:1512–1515, 1997320. Malmberg K, Ryden L, Efendic S, HerlitzJ, Nicol P, Waldenstrom A, Wedel H,Welin L: Randomized trial of insulin-glucose infusion followed by subcutane-ous insulin treatment in diabeticpatients with acute myocardial infarc-tion (DIGAMI study): effects on mortal-ity at 1 year. J Am Coll Cardiol 26:57–65,1995321. Malmberg K, Ryden L, Wedel H, Birke-land K, Bootsma A, Dickstein K, EfendicS, Fisher M, Hamsten A, Herlitz J, Hilde-brandt P, MacLeod K, Laakso M, Torp-Pedersen C, Waldenstrom A: Intensemetabolic control by means of insulin inpatients with diabetes mellitus and acutemyocardial infarction (DIGAMI 2): ef-fects on mortality and morbidity. EurHeart J 26:650–661, 2005322. Mehta SR, Yusuf S, Diaz R, Zhu J, Pais P,Xavier D, Paolasso E, Ahmed R, Xie C,Kazmi K, Tai J, Orlandini A, Pogue J, LiuL: Effect of glucose-insulin-potassiuminfusion on mortality in patients withacute ST-segment elevation myocardialinfarction: the CREATE-ECLA random-ized controlled trial. JAMA 293:437–446, 2005323. Cheung NW, Wong VW, McLean M:The hyperglycemia: intensive insulin in-fusion in infarction (HI-5) study: a ran-domized controlled trial of insulininfusion therapy for myocardial infarc-tion. Diabetes Care 29:765–770, 2006324. Furnary AP, Gao G, Grunkemeier GL,Wu Y, Zerr KJ, Bookin SO, Floten HS,Starr A: Continuous insulin infusion re-duces mortality in patients with diabetesundergoing coronary artery bypassgrafting. J Thorac Cardiovasc Surg 125:1007–1021, 2003325. Furnary AP, Zerr KJ, Grunkemeier GL,Starr A: Continuous intravenous insulininfusion reduces the incidence of deepsternal wound infection in diabetic pa-tients after cardiac surgical procedures.Ann Thorac Surg 67:352–360, 1999326. Golden SH, Peart-Vigilance C, Kao WH,Brancati FL: Perioperative glycemic con-trol and the risk of infectious complica-tions in a cohort of adults with diabetes.Diabetes Care 22:1408–1414, 1999327. Zerr KJ, Furnary AP, Grunkemeier GL,Bookin S, Kanhere V, Starr A: Glucosecontrol lowers the risk of wound infec-tion in diabetics after open heart opera-tions. Ann Thorac Surg 63:356–361,1997328. van den BG, Wouters P, Weekers F, Ver-waest C, Bruyninckx F, Schetz M, Vlas-selaers D, Ferdinande P, Lauwers P,Bouillon R: Intensive insulin therapy inthe critically ill patients. N Engl J Med345:1359–1367, 2001329. van den BG, Wouters PJ, Bouillon R,Weekers F, Verwaest C, Schetz M, Vlas-selaers D, Ferdinande P, Lauwers P:Outcome benefit of intensive insulintherapy in the critically ill: insulin doseversus glycemic control. Crit Care Med31:359–366, 2003330. van den BG, Wilmer A, Hermans G,Meersseman W, Wouters PJ, Milants I,Van Wijngaerden E, Bobbaers H, Bouil-lon R: Intensive insulin therapy in themedical ICU. N Engl J Med 354:449–461, 2006331. Brunkhorst FM, Engel C, Bloos F, Meier-Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S59
  • 48. Hellmann A, Ragaller M, Weiler N,Moerer O, Gruendling M, Oppert M,Grond S, Olthoff D, Jaschinski U, JohnS, Rossaint R, Welte T, Schaefer M, KernP, Kuhnt E, Kiehntopf M, Hartog C, Na-tanson C, Loeffler M, Reinhart K: Inten-sive insulin therapy and pentastarchresuscitation in severe sepsis. N EnglJ Med 358:125–139, 2008332. Pittas AG, Siegel RD, Lau J: Insulin ther-apy for critically ill hospitalized patients:a meta-analysis of randomized con-trolled trials. Arch Intern Med 164:2005–2011, 2004333. Wiener RS, Wiener DC, Larson RJ: Ben-efits and risks of tight glucose control incritically ill adults: a meta-analysis.JAMA 300:933–944, 2008334. Krinsley J: Glycemic control in criticallyill patients: Leuven and beyond. Chest132:1–2, 2007335. Miller CD, Phillips LS, Ziemer DC,Gallina DL, Cook CB, El Kebbi IM: Hy-poglycemia in patients with type 2 dia-betes mellitus. Arch Intern Med 161:1653–1659, 2001336. Misbin RI, Green L, Stadel BV, Guerigu-ian JL, Gubbi A, Fleming GA: Lactic ac-idosis in patients with diabetes treatedwith metformin. N Engl J Med 338:265–266, 1998337. Misbin RI: The phantom of lactic acido-sis due to metformin in patients with di-abetes. Diabetes Care 27:1791–1793,2004338. Salpeter SR, Greyber E, Pasternak GA,Salpeter EE: Risk of fatal and nonfatallactic acidosis with metformin use intype 2 diabetes mellitus: systematic re-view and meta-analysis. Arch Intern Med163:2594–2602, 2003339. Queale WS, Seidler AJ, Brancati FL: Gly-cemic control and sliding scale insulinuse in medical inpatients with diabetesmellitus. Arch Intern Med 157:545–552,1997340. Gearhart JG, Duncan JL, III, ReplogleWH, Forbes RC, Walley EJ: Efficacy ofsliding-scale insulin therapy: a compar-ison with prospective regimens. FamPract Res J 14:313–322, 1994341. Walts LF, Miller J, Davidson MB, BrownJ: Perioperative management of diabetesmellitus. Anesthesiology 55:104–109,1981342. Umpierrez GE, Smiley D, Zisman A, Pri-eto LM, Palacio A, Ceron M, Puig A, Me-jia R: Randomized study of basal-bolusinsulin therapy in the inpatient manage-ment of patients with type 2 diabetes(RABBIT 2 trial). Diabetes Care 30:2181–2186, 2007343. Schmeltz LR, DeSantis AJ, Schmidt K,O’Shea-Mahler E, Rhee C, Brandt S,Peterson S, Molitch ME: Conversion ofintravenous insulin infusions to subcu-taneously administered insulin glarginein patients with hyperglycemia. EndocrPract 12:641–650, 2006344. Shilo S, Berezovsky S, Friedlander Y,Sonnenblick M: Hypoglycemia in hospi-talized nondiabetic older patients. J AmGeriatr Soc 46:978–982, 1998345. Fischer KF, Lees JA, Newman JH: Hypo-glycemia in hospitalized patients: causesand outcomes. N Engl J Med 315:1245–1250, 1986346. Markovitz LJ, Wiechmann RJ, Harris N,Hayden V, Cooper J, Johnson G, Harel-stad R, Calkins L, Braithwaite SS: De-scription and evaluation of a glycemicmanagement protocol for patients withdiabetes undergoing heart surgery. En-docrPract 8:10–18, 2002347. Levetan CS, Salas JR, Wilets IF, ZumoffB: Impact of endocrine and diabetesteam consultation on hospital length ofstay for patients with diabetes. Am J Med99:22–28, 1995348. Levetan CS, Passaro MD, Jablonski KA,Ratner RE: Effect of physician specialtyon outcomes in diabetic ketoacidosis.Diabetes Care 22:1790–1795, 1999349. Koproski J, Pretto Z, Poretsky L: Effectsof an intervention by a diabetes team inhospitalized patients with diabetes. Dia-betes Care 20:1553–1555, 1997350. Furnary AP, Braithwaite SS: Effects ofoutcome on in-hospital transition fromintravenous insulin infusion to subcuta-neous therapy. Am J Cardiol 98:557–564, 2006351. American Diabetes Association: Diabe-tes nutrition recommendations forhealth care institutions (Position State-ment). Diabetes Care 27 (Suppl. 1):S55–S57, 2004352. Boucher JL, Swift CS, Franz MJ,Kulkarni K, Schafer RG, Pritchett E,Clark NG: Inpatient management of di-abetes and hyperglycemia: implicationsfor nutrition practice and the food andnutrition professional. J Am Diet Assoc107:105–111, 2007353. American Diabetes Association: Diabe-tes care in the school and day care set-ting. Diabetes Care 29 (Suppl. 1):S49–S55, 2006354. National Diabetes Education Program:Helping the student with diabetes suc-ceed: a guide for school personnel (arti-cle online), 2006. Available from American Diabetes Association: Diabe-tes care tasks at school: what key person-nel need to know (article online), 2005.Available from http://diabetes.org356. American Diabetes Association: Diabe-tes care at diabetes camps. Diabetes Care29 (Suppl. 1):S56–S58, 2006357. American Diabetes Association: Diabe-tes management in correctional institu-tions. Diabetes Care 29 (Suppl. 1):S59–S66, 2006358. American Diabetes Association State-ment on Emergency and Disaster Pre-paredness: a report of the DisasterResponse Task Force. Diabetes Care 30:2395–2398, 2007359. Cefalu WT, Smith SR, Blonde L, FonsecaV: The Hurricane Katrina aftermath andits impact on diabetes care: observationsfrom “ground zero”: lessons in disasterpreparedness of people with diabetes.Diabetes Care 29:158–160, 2006360. American Diabetes Association: Hypo-glycemia and employment/licensure.Diabetes Care 29 (Suppl. 1):S67, 2006361. American Diabetes Association: Third-party reimbursement for diabetes care,self-management education, and sup-plies. Diabetes Care 29 (Suppl. 1):S68–S69, 2006362. Saydah SH, Fradkin J, Cowie CC: Poorcontrol of risk factors for vascular dis-ease among adults with previously diag-nosed diabetes. JAMA 291:335–342,2004363. Clark CM Jr, Snyder JW, Meek RL, StutzLM, Parkin CG: A systematic approachto risk stratification and interventionwithin a managed care environment im-proves diabetes outcomes and patientsatisfaction. Diabetes Care 24:1079–1086, 2001364. Meigs JB, Cagliero E, Dubey A, Murphy-Sheehy P, Gildesgame C, Chueh H,Barry MJ, Singer DE, Nathan DM: A con-trolled trial of web-based diabetes dis-ease management: the MGH diabetesprimary care improvement project. Dia-betes Care 26:750–757, 2003365. O’Connor PJ, Desai J, Solberg LI, RegerLA, Crain AL, Asche SE, Pearson TL,Clark CK, Rush WA, Cherney LM,Sperl-Hillen JM, Bishop DB: Random-ized trial of quality improvement inter-vention to improve diabetes care inprimary care settings. Diabetes Care 28:1890–1897, 2005366. Sperl-Hillen JM, O’Connor PJ: Factorsdriving diabetes care improvement in alarge medical group: ten years ofprogress. Am J Manag Care 11:S177–S185, 2005367. Siminerio LM: Implementing diabetesself-management training programs:breaking through the barriers in primarycare. Endocr Pract 12 (Suppl. 1):124–130, 2006368. Mahoney JJ: Reducing patient drug ac-quisition costs can lower diabetes healthclaims. Am J Manag Care 11:S170–S176,2005369. Maney M, Tseng CL, Safford MM, MillerDR, Pogach LM: Impact of self-reportedpatient characteristics upon assessmentof glycemic control in the VeteransHealth Administration. Diabetes Care30:245–251, 2007Standards of Medical CareS60 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 49. 370. Bergenstal RM: Treatment models fromthe International Diabetes Center: ad-vancing from oral agents to insulin ther-apy in type 2 diabetes. Endocr Pract 12(Suppl. 1):98–104, 2006371. O’Connor PJ: Electronic medical recordsand diabetes care improvement: are wewaiting for Godot? Diabetes Care26:942–943, 2003372. Shojania KG, Ranji SR, McDonald KM,Grimshaw JM, Sundaram V, RushakoffRJ, Owens DK: Effects of quality im-provement strategies for type 2 diabeteson glycemic control: a meta-regressionanalysis. JAMA 296:427–440, 2006Position StatementDIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S61