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  • 1. P O S I T I O N S T A T E M E N T Standards of Medical Care in Diabetes—2009 AMERICAN DIABETES ASSOCIATION I. CLASSIFICATION AND D iabetes is a chronic illness that re- B. Diagnosis of diabetes quires continuing medical care DIAGNOSIS Current criteria for the diagnosis of diabetes and patient self-management ed- in nonpregnant adults are shown in Table 2. ucation to prevent acute complications A. Classification Three ways to diagnose diabetes are recom- and to reduce the risk of long-term In 1997, ADA issued new diagnostic and mended at the time of this statement, and complications. Diabetes care is complex classification criteria (4); in 2003, modi- each must be confirmed on a subsequent and requires that many issues, beyond fications were made regarding the diagno- day unless unequivocal symptoms of hy- glycemic control, be addressed. A large sis of impaired fasting glucose (5). The perglycemia are present. Although the 75-g body of evidence exists that supports a classification of diabetes includes four oral glucose tolerance test (OGTT) is more range of interventions to improve dia- clinical classes: sensitive and modestly more specific than betes outcomes. the fasting plasma glucose (FPG) to diag- These standards of care are in- ● type 1 diabetes (results from -cell de- nose diabetes, it is poorly reproducible and tended to provide clinicians, patients, struction, usually leading to absolute difficult to perform in practice. Because of researchers, payors, and other inter- insulin deficiency) ease of use, acceptability to patients, and ested individuals with the components ● type 2 diabetes (results from a progres- lower cost, the FPG has been the preferred of diabetes care, treatment goals, and sive insulin secretory defect on the diagnostic test. Though FPG is less sensitive tools to evaluate the quality of care. background of insulin resistance) than the OGTT, the vast majority of people While individual preferences, comor- ● who do not meet diagnostic criteria for dia- other specific types of diabetes due to bidities, and other patient factors may betes by FPG but would by OGTT will have other causes, e.g., genetic defects in an A1C value well under 7.0% (6). require modification of goals, targets -cell function, genetic defects in insu- Though the OGTT is not recom- that are desirable for most patients with lin action, diseases of the exocrine pan- mended for routine clinical use, it may be diabetes are provided. These standards creas (such as cystic fibrosis), and drug- useful for further evaluation of patients in are not intended to preclude more ex- or chemical-induced (such as in the whom diabetes is still strongly suspected tensive evaluation and management of treatment of AIDS or after organ trans- but who have normal FPG or IFG (see the patient by other specialists as plantation) Section I.C). needed. For more detailed information, ● gestational diabetes mellitus (GDM) The use of the A1C for the diagnosis refer to references 1–3. (diabetes diagnosed during pregnancy) of diabetes has previously not been rec- The recommendations included are ommended due to lack of global stan- screening, diagnostic, and therapeutic Some patients cannot be clearly classified as dardization and uncertainty about actions that are known or believed to type 1 or type 2 diabetes. Clinical presenta- diagnostic thresholds. However, with a favorably affect health outcomes of pa- tion and disease progression vary consider- world-wide move toward a standardized tients with diabetes. A grading system ably in both types of diabetes. Occasionally, assay and with increasing observational (Table 1), developed by the American patients who otherwise have type 2 diabetes evidence about the prognostic signifi- Diabetes Association (ADA) and mod- may present with ketoacidosis. Similarly, cance of A1C, an Expert Committee on eled after existing methods, was utilized patients with type 1 may have a late onset the Diagnosis of Diabetes was convened to clarify and codify the evidence that and slow (but relentless) progression of dis- in 2008. This joint committee of ADA, the forms the basis for the recommenda- ease despite having features of autoimmune European Association for the Study of Di- tions. The level of evidence that sup- disease. Such difficulties in diagnosis may abetes, and the International Diabetes ports each recommendation is listed occur in children, adolescents, and adults. Federation will likely recommend that the after each recommendation using the The true diagnosis may become more obvi- A1C become the preferred diagnostic test letters A, B, C, or E. ous over time. for diabetes. Diagnostic cut-points are be- ing discussed at the time of publication of this statement. Updated recommenda- ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● tions will be published in Diabetes Care The recommendations in this article are based on the evidence reviewed in the following publication: and will be available at diabetes.org. 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 properly C. Diagnosis of pre-diabetes cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons. Hyperglycemia not sufficient to meet the org/licenses/by-nc-nd/3.0/ for details. diagnostic criteria for diabetes is catego- DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S13
  • 2. Standards of Medical Care Table 1—ADA evidence grading system for clinical practice recommendations same tests would be used for “screening” as for diagnosis. Type 2 diabetes has a Level of long asymptomatic phase and significant evidence Description clinical risk markers. Diabetes may be identified anywhere along a spectrum of A Clear evidence from well-conducted, generalizable, randomized controlled clinical scenarios ranging from a seem- trials that are adequately powered, including: ingly low-risk individual who happens to ● Evidence from a well-conducted multicenter trial have glucose testing, to a higher-risk in- ● Evidence from a meta-analysis that incorporated quality ratings in the dividual whom the provider tests because analysis Compelling nonexperimental evidence, i.e., “all or none” rule developed of high suspicion of diabetes, to the symp- by the Centre for Evidence-Based Medicine at Oxford tomatic patient. The discussion herein is Supportive evidence from well-conducted randomized controlled trials primarily framed as testing for diabetes in that are adequately powered, including: those without symptoms. Testing for dia- ● Evidence from a well-conducted trial at one or more institutions ● Evidence from a meta-analysis that incorporated quality ratings in the betes will also detect individuals with pre- analysis diabetes. B Supportive evidence from well-conducted cohort studies, including: ● Evidence from a well-conducted prospective cohort study or registry A. Testing for pre-diabetes and type ● Evidence from a well-conducted meta-analysis of cohort studies 2 diabetes in adults Supportive evidence from a well-conducted case-control study Type 2 diabetes is frequently not diag- C Supportive evidence from poorly controlled or uncontrolled studies nosed until complications appear, and ● Evidence from randomized clinical trials with one or more major or approximately one-third of all people three or more minor methodological flaws that could invalidate the with diabetes may be undiagnosed. Al- results though the effectiveness of early identifi- ● Evidence from observational studies with high potential for bias (such as case series with comparison to historical controls) cation of pre-diabetes and diabetes ● Evidence from case series or case reports through mass testing of asymptomatic in- Conflicting evidence with the weight of evidence supporting the dividuals has not been definitively proven recommendation (and rigorous trials to provide such proof E Expert consensus or clinical experience are unlikely to occur), pre-diabetes and diabetes meet established criteria for con- ditions in which early detection is appro- rized as either impaired fasting glucose be carried out at least at 3-year inter- priate. Both conditions are common, (IFG) or impaired glucose tolerance vals. (E) increasing in prevalence, and impose sig- (IGT), depending on whether it is identi- ● To test for pre-diabetes or diabetes, an nificant public health burdens. There is a fied through the FPG or the OGTT: FPG test or 2-h OGTT (75-g glucose long presymptomatic phase before the di- load) or both are appropriate. (B) agnosis of type 2 diabetes is usually made. ● IFG FPG 100 mg/dl (5.6 mmol/l) to ● An OGTT may be considered in pa- Relatively simple tests are available to de- 125 mg/dl (6.9 mmol/l) tients with IFG to better define the risk tect preclinical disease (8). Additionally, ● IGT 2-h plasma glucose 140 mg/dl of diabetes. (E) the duration of glycemic burden is a (7.8 mmol/l) to 199 mg/dl (11.0 ● In those identified with pre-diabetes, strong predictor of adverse outcomes, mmol/l) identify and, if appropriate, treat other and effective interventions exist to pre- CVD risk factors. (B) vent progression of pre-diabetes to diabe- IFG and IGT have been officially termed tes (see Section IV) and to reduce risk of “pre-diabetes.” Both categories of pre- For many illnesses, there is a major dis- complications of diabetes (see Section diabetes are risk factors for future diabetes tinction between screening and diagnos- VI). and for cardiovascular disease (CVD) (7). tic testing. However, for diabetes, the Recommendations for testing for pre- II. TESTING FOR PRE- Table 2—Criteria for the diagnosis of diabetes DIABETES AND DIABETES IN ASYMPTOMATIC 1. FPG 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at PATIENTS least 8 h.* OR Recommendations 2. Symptoms of hyperglycemia and a casual (random) plasma glucose 200 ● Testing to detect pre-diabetes and type mg/dl (11.1 mmol/l). Casual (random) is defined as any time of day without 2 diabetes in asymptomatic people regard to time since last meal. The classic symptoms of hyperglycemia should be considered in adults of any include polyuria, polydipsia, and unexplained weight loss. age who are overweight or obese (BMI OR 25 kg/m2) and who have one or more 3. 2-h plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT. The test additional risk factors for diabetes (Ta- should be performed as described by the World Health Organization using ble 3). In those without these risk fac- a glucose load containing the equivalent of 75-g anhydrous glucose tors, testing should begin at age 45 dissolved in water.* years. (B) *In the absence of unequivocal hyperglycemia, these criteria should be confirmed by repeat testing on a ● If tests are normal, repeat testing should different day (5). S14 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 3. Position Statement Table 3—Criteria for testing for pre-diabetes and diabetes in asymptomatic adult individuals relatives with type 1 diabetes, in the context 1. 2 Testing should be considered in all adults who are overweight (BMI 25 kg/m *) and of clinical research studies (see, for exam- have additional risk factors: ple, http://www2.diabetestrialnet.org). ● physical inactivity Widespread clinical testing of asymptom- ● first-degree relative with diabetes atic low-risk individuals cannot currently ● members of a high-risk ethnic population (e.g., African American, Latino, Native be recommended, as it would identify very American, Asian American, Pacific Islander) few individuals in the general population ● women who delivered a baby weighing 9 lb or were diagnosed with GDM who are at risk. Individuals who screen pos- ● hypertension ( 140/90 mmHg or on therapy for hypertension) ● HDL cholesterol level 35 mg/dl (0.90 mmol/l) and/or a triglyceride level 250 itive should be counseled about their risk of mg/dl (2.82 mmol/l) developing diabetes. Clinical studies are be- ● women with polycystic ovarian syndrome (PCOS) ing conducted to test various methods of ● IGT or IFG on previous testing preventing type 1 diabetes, or reversing ● other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) early type 1 diabetes, in those with evidence ● history of CVD of autoimmunity. 2. In the absence of the above criteria, testing for pre-diabetes and diabetes should begin at age 45 years III. DETECTION AND 3. If results are normal, testing should be repeated at least at 3-year intervals, with DIAGNOSIS OF GDM consideration of more frequent testing depending on initial results and risk status. *At-risk BMI may be lower in some ethnic groups. Recommendations ● Screen for GDM using risk factor anal- ysis and, if appropriate, use of an diabetes and diabetes in asymptomatic, tests may not seek, or have access to, ap- OGTT. (C) undiagnosed adults are listed in Table 3. propriate follow-up testing and care. ● Women with GDM should be screened Testing should be considered in adults of Conversely, there may be failure to ensure for diabetes 6 –12 weeks postpartum any age with BMI 25 kg/m2 and one or appropriate repeat testing for individuals and should be followed up with subse- more risk factors for diabetes. Because age who test negative. Community screening quent screening for the development of is a major risk factor for diabetes, testing may also be poorly targeted, i.e., it may diabetes or pre-diabetes. (E) of those without other risk factors should fail to reach the groups most at risk and begin no later than age 45 years. inappropriately test those at low risk (the GDM is defined as any degree of glucose Either FPG testing or the 2-h OGTT is worried well) or even those already diag- intolerance with onset or first recognition appropriate for testing. The 2-h OGTT nosed (18,19). during pregnancy (4). Although most identifies people with either IFG or IGT, cases resolve with delivery, the definition and thus, more pre-diabetic people at in- B. Testing for type 2 diabetes in applies whether or not the condition per- creased risk for the development of dia- children sists after pregnancy and does not exclude betes and CVD. It should be noted that The incidence of type 2 diabetes in ado- the possibility that unrecognized glucose the two tests do not necessarily detect the lescents has increased dramatically in the intolerance may have antedated or begun same pre-diabetic individuals (9). The ef- last decade, especially in minority popu- concomitantly with the pregnancy. Ap- ficacy of interventions for primary pre- lations (20), although the disease remains vention of type 2 diabetes (10 –16) has rare in the general adolescent population primarily been demonstrated among in- (21). Consistent with recommendations Table 4—Testing for type 2 diabetes in dividuals with IGT, not individuals with for adults, children and youth at in- asymptomatic children IFG (who do not also have IGT). As noted creased risk for the presence or the devel- Criteria: in the diagnosis section (Section I.B), the opment of type 2 diabetes should be ● Overweight (BMI 85th percentile for FPG test is more convenient, more repro- tested within the health care setting (22). age and sex, weight for height 85th ducible, less costly, and easier to admin- The recommendations of the ADA con- percentile, or weight 120% of ideal for ister than the 2-h OGTT (4,5). An OGTT sensus statement on type 2 diabetes in height) may be useful in patients with IFG to bet- children and youth, with some modifica- Plus any two of the following risk factors: ter define the risk of diabetes. tions, are summarized in Table 4. ● Family history of type 2 diabetes in first- or second-degree relative The appropriate interval between ● Race/ethnicity (Native American, African tests is not known (17). The rationale for C. Screening for type 1 diabetes American, Latino, Asian American, Pacific the 3-year interval is that false-negatives Generally, people with type 1 diabetes Islander) will be repeated before substantial time present with acute symptoms of diabetes ● Signs of insulin resistance or conditions elapses, and there is little likelihood that and markedly elevated blood glucose lev- associated with insulin resistance (acanthosis nigricans, hypertension, an individual will develop significant els, and most cases are diagnosed soon dyslipidemia, PCOS, or small-for- complications of diabetes within 3 years after the onset of hyperglycemia. How- gestational-age birthweight) of a negative test result. ever, evidence from type 1 prevention ● Maternal history of diabetes or GDM Because of the need for follow-up and studies suggests that measurement of islet during the child’s gestation discussion of abnormal results, testing autoantibodies identifies individuals who Age of initiation: age 10 years or at onset of should be carried out within the health are at risk for developing type 1 diabetes. puberty, if puberty occurs at a younger care setting. Community screening out- Such testing may be appropriate in high- age side a health care setting is not recom- risk individuals, such as those with prior Frequency: every 3 years mended because people with positive transient hyperglycemia or those who have Test: FPG preferred DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S15
  • 4. Standards of Medical Care Table 5—Screening for and diagnosis of GDM IV. PREVENTION/DELAY Carry out GDM risk assessment at the first prenatal visit. OF TYPE 2 DIABETES Women at very high risk for GDM should be screened for diabetes as soon as possible after the confirmation of pregnancy. Criteria for very high risk are: Recommendations ● Patients with IGT (A) or IFG (E) should ● severe obesity ● prior history of GDM or delivery of large-for-gestational-age infant be referred to an effective ongoing sup- ● presence of glycosuria port program for weight loss of 5–10% ● diagnosis of PCOS of body weight and for increasing phys- ● strong family history of type 2 diabetes ical activity to at least 150 min per week Screening/diagnosis at this stage of pregnancy should use standard diagnostic testing (Table 2). of moderate activity such as walking. ● Follow-up counseling appears to be im- All women of greater than low risk of GDM, including those above not found to have diabetes early in pregnancy, should undergo GDM testing at 24–28 weeks of gestation. portant for success. (B) ● Based on potential cost savings of dia- Low risk status, which does not require GDM screening, is defined as women with ALL of the following characteristics: betes prevention, such counseling ● age 25 years should be covered by third-party pay- ● weight normal before pregnancy ors. (E) ● In addition to lifestyle counseling, met- ● member of an ethnic group with a low prevalence of diabetes ● no known diabetes in first-degree relatives formin may be considered in those who ● no history of abnormal glucose tolerance are at very high risk for developing di- ● no history of poor obstetrical outcome abetes (combined IFG and IGT plus Two approaches may be followed for GDM screening at 24–28 weeks: other risk factors such as A1C 6%, 1. Two-step approach: hypertension, low HDL cholesterol, el- A. Perform initial screening by measuring plasma or serum glucose 1 h after a 50-g oral evated triglycerides, or family history of glucose load. A glucose threshold after 50-g load of 140 mg/dl identifies 80% of diabetes in a first-degree relative) and women with GDM, while the sensitivity is further increased to 90% by a threshold of who are obese and under 60 years of 130 mg/dl. age. (E) ● Monitoring for the development of di- B. Perform a diagnostic 100-g OGTT on a separate day in women who exceed the chosen threshold on 50-g screening. abetes in those with pre-diabetes 2. One-step approach (may be preferred in clinics with high prevalence of GDM): Perform should be performed every year. (E) a 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. Randomized controlled trials have shown To make a diagnosis of GDM, at least two of the following plasma glucose values must be found: that individuals at high risk for develop- Fasting: 95 mg/dl ing diabetes (those with IFG, IGT, or 1 h: 180 mg/dl both) can be given interventions that sig- 2 h: 155 mg/dl nificantly decrease the rate of onset of di- 3 h: 140 mg/dl abetes (10 –16). These interventions include intensive lifestyle modification programs that have been shown to be very proximately 7% of all pregnancies (rang- These results have led to careful reconsid- effective ( 58% reduction after 3 years) ing from 1 to 14% depending on the eration of the diagnostic criteria for GDM. and use of the pharmacologic agents met- population studied and the diagnostic An international group representing mul- formin, acarbose, orlistat, and thiazo- tests employed) are complicated by GDM, tiple obstetrical and diabetes organiza- lidinediones (TZDs), each of which has resulting in more than 200,000 cases tions, including ADA, is currently been shown to decrease incident diabetes annually. working on consensus toward 1) a world- to various degrees. A summary of major Because of the risks of GDM to the wide standard for which diagnostic test to diabetes prevention trials is shown in Ta- mother and neonate, screening and di- use for GDM and 2) rational diagnostic ble 6. agnosis are warranted. The screening cut points. Two studies of lifestyle intervention and diagnostic strategies, based on the Because women with a history of have shown persistent reduction in the 2004 ADA position statement on gesta- rate of conversion to type 2 diabetes with GDM have a greatly increased subse- tional diabetes mellitus (23), are outlined in 3 (26) to 14 years (27) of postintervention quent risk for diabetes (25), they should Table 5. follow-up. Results of the Hyperglycemia and Ad- be screened for diabetes 6 –12 weeks Based on the results of clinical trials verse Pregnancy Outcomes study (24), a postpartum, using nonpregnant OGTT and the known risks of progression of large-scale (including 25,000 pregnant criteria, and should be followed up with pre-diabetes to diabetes, an ADA Consen- women) multinational epidemiologic subsequent screening for the develop- sus Development Panel (7) concluded study, demonstrated that risk of adverse ment of diabetes or pre-diabetes, as out- that persons with pre-diabetes (IGT maternal, fetal, and neonatal outcomes lined in Section II. For information on and/or IFG) should be counseled on life- continuously increased as a function of the National Diabetes Education Pro- style changes with goals similar to those of maternal glycemia at 24 –28 weeks, even gram (NDEP) campaign to prevent type the Diabetes Prevention Program (DPP) within ranges previously considered nor- 2 diabetes in women with GDM, go to (5–10% weight loss and moderate physi- mal for pregnancy. For most complica- www.ndep.nih.gov/diabetes/pubs/ cal activity of 30 min per day). Regard- tions, there was no threshold for risk. NeverTooEarly_Tipsheet.pdf. ing the more difficult issue of drug S16 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 5. Position Statement Table 6—Therapies proven effective in diabetes prevention trials Mean Conversion in age Duration Intervention control subjects Study (ref.) n Population (years) (years) (daily dose) (%/year) Relative risk Lifestyle Finnish DPS (11) 522 IGT, BMI 25 kg/m2 55 3.2 Individual 6 0.42 (0.30–0.70) diet/exercise DPP (10) 2,161* IGT, BMI 24 kg/m2, 51 3 Individual 10 0.42 (0.34–0.52) FPG 5.3 mmol/l diet/exercise Da Qing (12) 259* IGT (randomized 45 6 Group diet/exercise 16 0.62 (0.44–0.86) groups) Toranomon study (28) 458 IGT (men), BMI 24 55 4 Individual 2 0.33 (0.10–1.0)† kg/m2 diet/exercise Indian DPP (16) 269* IGT 46 2.5 Individual 22 0.71 (0.63–0.79) diet/exercise Medications DPP (10) 2,155* IGT, BMI 24 kg/m2, 51 2.8 Metformin (1,700 mg) 10 0.69 (0.57–0.83) FPG 5.3 mmol/l 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 5.6 mmol/l 54 3.2 Acarbose (300 mg) 13 0.75 (0.63–0.90) XENDOS (29) 3,277 BMI 30 kg/m2 43 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 Prevention Program; DREAM, Diabetes REduction Assessment with ramipril and rosiglitazone Medication; DPS, Diabetes Prevention Study; STOP NIDDM, Study to Prevent Non-Insulin Dependent Diabetes; XENDOS, Xenical in the prevention of Diabetes in Obese Subjects. This table has been reprinted with permission (30) with some modification. therapy for diabetes prevention, the con- ensure optimal management of the pa- patient’s age, school or work schedule sensus panel felt that metformin should tient with diabetes. and conditions, physical activity, eating be the only drug considered for use in patterns, social situation and personality, diabetes prevention. For other drugs, the B. Management cultural factors, and presence of compli- issues of cost, side effects, and lack of per- People with diabetes should receive med- cations of diabetes or other medical con- sistence of effect in some studies led the ical care from a physician-coordinated ditions. panel to not recommend their use for di- team. Such teams may include, but are abetes prevention. Metformin use was not limited to, physicians, nurse practitio- C. Glycemic control recommended only for very-high-risk in- ners, physician’s assistants, nurses, dieti- dividuals (those with combined IGT and tians, pharmacists, and mental health 1. Assessment of glycemic control IFG who are obese and under 60 years of professionals with expertise and a special Two primary techniques are available for age with at least one other risk factor for interest in diabetes. It is essential in this health providers and patients to assess the diabetes). In addition, the panel high- collaborative and integrated team ap- effectiveness of the management plan on lighted the evidence that in the DPP, met- proach that individuals with diabetes as- glycemic control: patient self-monitoring formin was most effective compared to sume an active role in their care. of blood glucose (SMBG) or of interstitial lifestyle in those with BMI of at least 35 The management plan should be for- glucose and measurement of A1C. kg/m2 and those under age 60 years. mulated as an individualized therapeutic alliance among the patient and family, the a. Glucose monitoring V. DIABETES CARE physician, and other members of the health care team. A variety of strategies Recommendations A. Initial evaluation and techniques should be used to provide ● SMBG should be carried out three or A complete medical evaluation should be adequate education and development of more times daily for patients using mul- performed to classify the diabetes, detect problem-solving skills in the various as- tiple insulin injections or insulin pump the presence of diabetes complications, pects of diabetes management. Imple- therapy. (A) review previous treatment and glycemic mentation of the management plan ● For patients using less frequent insulin control in patients with established diabe- requires that each aspect is understood injections, noninsulin therapies, or tes, assist in formulating a management and agreed on by the patient and the care medical nutrition therapy (MNT) and plan, and provide a basis for continuing providers and that the goals and treat- physical activity alone, SMBG may be care. Laboratory tests appropriate to the ment plan are reasonable. Any plan useful as a guide to the success of ther- evaluation of each patient’s medical con- should recognize diabetes self-manage- apy. (E) dition should be performed. A focus on ment education (DSME) as an integral ● To achieve postprandial glucose tar- the components of comprehensive care component of care. In developing the gets, postprandial SMBG may be appro- (Table 7) will assist the health care team to plan, consideration should be given to the priate. (E) DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S17
  • 6. Standards of Medical Care Table 7—Components of the comprehensive diabetes evaluation their individual response to therapy and Medical history assess whether glycemic targets are being ● age and characteristics of onset of diabetes (e.g., DKA, asymptomatic laboratory finding) achieved. Results of SMBG can be useful ● eating patterns, physical activity habits, nutritional status, and weight history; growth in preventing hypoglycemia and adjust- and development in children and adolescents ing medications (particularly prandial in- ● diabetes education history sulin doses), MNT, and physical activity. ● review of previous treatment regimens and response to therapy (A1C records) The frequency and timing of SMBG ● current treatment of diabetes, including medications, meal plan, physical activity should be dictated by the particular needs patterns, and results of glucose monitoring and patient’s use of data and goals of the patients. SMBG is espe- ● DKA frequency, severity, and cause cially important for patients treated with ● hypoglycemic episodes insulin to monitor for and prevent asymp- ● hypoglycemia awareness tomatic hypoglycemia and hyperglyce- ● any severe hypoglycemia: frequency and cause mia. For most patients with type 1 ● history of diabetes-related complications diabetes and pregnant women taking in- ● microvascular: retinopathy, nephropathy, neuropathy (sensory, including history of sulin, SMBG is recommended three or foot lesions; autonomic, including sexual dysfunction and gastroparesis) more times daily. For this population, sig- ● macrovascular: CHD, cerebrovascular disease, PAD nificantly more frequent testing may be ● other: psychosocial problems,* dental disease* required to reach A1C targets safely with- Physical examination out hypoglycemia. The optimal frequency ● height, weight, BMI and timing of SMBG for patients with type ● blood pressure determination, including orthostatic measurements when indicated 2 diabetes on noninsulin therapy is un- ● fundoscopic examination* clear. A meta-analysis of SMBG in non– ● thyroid palpation insulin-treated patients with type 2 ● skin examination (for acanthosis nigricans and insulin injection sites) diabetes concluded that some regimen of ● comprehensive foot examination: SMBG was associated with a reduction in ● inspection A1C of 0.4%. However, many of the ● palpation of dorsalis pedis and posterior tibial pulses studies in this analysis also included pa- ● presence/absence of patellar and Achilles reflexes tient education with diet and exercise ● determination of proprioception, vibration, and monofilament sensation counseling and, in some cases, pharma- Laboratory evaluation cologic intervention, making it difficult to ● A1C, if results not available within past 2–3 months assess the contribution of SMBG alone to If not performed/available within past year: improved control (33). Several recent tri- ● fasting lipid profile, including total, LDL- and HDL-cholesterol and triglycerides als have called into question the clinical ● liver function tests utility and cost-effectiveness of routine ● test for urine albumin excretion with spot urine albumin/creatinine ratio SMBG in non–insulin-treated patients ● serum creatinine and calculated GFR (34 –36). ● thyroid-stimulating hormone in type 1 diabetes, dyslipidemia or women over age 50 Because the accuracy of SMBG is instru- Referrals ment and user dependent (37), it is impor- ● annual dilated eye exam tant to evaluate each patient’s monitoring ● family planning for women of reproductive age technique, both initially and at regular in- ● registered dietitian for MNT tervals thereafter. In addition, optimal use ● diabetes self-management education of SMBG requires proper interpretation of ● dental examination the data. Patients should be taught how to ● mental Health professional, if needed use the data to adjust food intake, exercise, *See appropriate referrals for these categories. or pharmacological therapy to achieve spe- cific glycemic goals, and these skills should be reevaluated periodically. ● When prescribing SMBG, ensure that ● CGM may be a supplemental tool to CGM through the measurement of in- patients receive initial instruction in, SMBG in those with hypoglycemia un- terstitial glucose (which correlates well and routine follow-up evaluation of, awareness and/or frequent hypoglyce- with plasma glucose) is available. These SMBG technique and their ability to use mic episodes. (E) sensors require calibration with SMBG, data to adjust therapy. (E) and the latter are still recommended for ● Continuous glucose monitoring (CGM) The ADA’s consensus and position state- making acute treatment decisions. CGM in conjunction with intensive insulin ments on SMBG provide a comprehensive devices also have alarms for hypo- and regimens can be a useful tool to lower review of the subject (31,32). Major clin- hyperglycemic excursions. Small studies A1C in selected adults (age 25 years) ical trials of insulin-treated patients that in selected patients with type 1 diabetes with type 1 diabetes (A). demonstrated the benefits of intensive have suggested that CGM use reduces the ● Although the evidence for A1C lowering glycemic control on diabetes complica- time spent in hypo- and hyperglycemic is less strong in children, teens, and tions have included SMBG as part of mul- ranges and may modestly improve glyce- younger adults, CGM may be helpful in tifactorial interventions, suggesting that mic control. A larger 26-week random- these groups. Success correlates with ad- SMBG is a component of effective ther- ized trial of 322 type 1 patients showed herence to ongoing use of the device. (C) apy. SMBG allows patients to evaluate that adults age 25 years and older using S18 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 7. Position Statement intensive insulin therapy and CGM expe- Table 8—Correlation of A1C with average ferent, as they are based on 2,800 read- rienced a 0.5% reduction in A1C (from glucose ings per A1C in the ADAG trial. 7.6 to 7.1%) compared with usual in- In the ADAG study, there were no sig- tensive insulin therapy with SMBG (38). Mean plasma glucose nificant differences among racial and eth- Sensor use in children, teens, and adults nic groups in the regression lines between to age 24 years did not result in significant A1C (%) mg/dl mmol/l A1C and mean glucose, although there A1C lowering, and there was no signifi- 6 126 7.0 was a trend toward a difference between cant difference in hypoglycemia in any 7 154 8.6 African/African-American and Caucasian group. Importantly, the greatest predictor 8 183 10.2 participants’ regression lines that might of A1C lowering in this study for all age- 9 212 11.8 have been significant had more African/ groups was frequency of sensor use, 10 240 13.4 African-American participants been stud- which was lower in younger age-groups. 11 269 14.9 ied. A recent study comparing A1C to Although CGM is an evolving technology, 12 298 16.5 CGM data in 48 type 1 children found a emerging data suggest that, in appropri- Estimates based on ADAG data of 2,700 glucose highly statistically significant correlation ately selected patients who are motivated measurements over 3 months per A1C measure- between A1C and mean blood glucose, to wear it most of the time, it may offer ment in 507 adults with type 1, type 2, and no dia- although the correlation (r 0.7) was sig- benefit. CGM may be particularly useful betes. Correlation between A1C and average nificantly lower than in the ADAG trial in those with hypoglycemia unawareness glucose: 0.92 (42). A calculator for converting A1C (44). Whether there are significant differ- results into eAG, in either mg/dl or mmol/l, is avail- and/or frequent episodes of hypoglyce- able at http://professional.diabetes.org/eAG. ences in how A1C relates to average glu- mia, and studies in this area are ongoing. cose in children or in African-American patients is an area for further study. For b. A1C itations. Conditions that affect erythro- the time being, the question has not led to cyte turnover (hemolysis, blood loss) and different recommendations about testing Recommendations hemoglobin variants must be considered, A1C or to different interpretations of the ● Perform the A1C test at least two times particularly when the A1C result does not clinical meaning of given levels of A1C in a year in patients who are meeting treat- correlate with the patient’s clinical situa- those populations. ment goals (and who have stable glyce- tion (37). In addition, A1C does not pro- For patients in whom A1C/eAG and mic control). (E) vide a measure of glycemic variability or measured blood glucose appear discrep- ● Perform the A1C test quarterly in pa- hypoglycemia. For patients prone to gly- ant, clinicians should consider the possi- tients whose therapy has changed or cemic variability (especially type 1 pa- bilities of hemoglobinopathy or altered who are not meeting glycemic goals. (E) tients, or type 2 patients with severe red cell turnover and the options of more ● Use of point-of-care testing for A1C al- insulin deficiency), glycemic control is frequent and/or different timing of SMBG lows for timely decisions on therapy best judged by the combination of results or use of CGM. Other measures of chronic changes, when needed. (E) of SMBG testing and the A1C. The A1C glycemia such as fructosamine are avail- may also serve as a check on the accuracy able, but their linkage to average glucose Because A1C is thought to reflect average of the patient’s meter (or the patient’s re- and their prognostic significance are not glycemia over several months (37), and ported SMBG results) and the adequacy of as clear as is the case for A1C. has strong predictive value for diabetes the SMBG testing schedule. complications (10,39), A1C testing Table 8 contains the correlation be- should be performed routinely in all pa- tween A1C levels and mean plasma glu- 2. Glycemic goals in adults tients with diabetes at initial assessment cose levels based on data from the ● Lowering A1C to below or around 7% and then as part of continuing care. Mea- international A1C-Derived Average Glu- has been shown to reduce microvascu- surement approximately every 3 months cose (ADAG) trial utilizing frequent lar and neuropathic complications of determines whether a patient’s glycemic SMBG and continuous glucose monitor- type 1 and type 2 diabetes. Therefore, targets have been reached and main- ing in 507 adults (83% Caucasian) with for microvascular disease prevention, tained. For any individual patient, the fre- type 1, type 2, and no diabetes (49) The the A1C goal for nonpregnant adults in quency of A1C testing should be ADA and American Association of Clini- general is 7%. (A) dependent on the clinical situation, the cal Chemists have determined that the ● In type 1 and type 2 diabetes, random- treatment regimen used, and the judg- correlation (r 0.92) is strong enough to ized controlled trials of intensive versus ment of the clinician. Some patients with justify reporting both an A1C result and standard glycemic control have not stable glycemia well within target may do an estimated average glucose (eAG) result shown a significant reduction in CVD well with testing only twice per year, when a clinician orders the A1C test. The outcomes during the randomized por- while unstable or highly intensively man- table in previous versions of the Stan- tion of the trials. Long-term follow-up aged patients (e.g., pregnant type 1 dards of Medical Care in Diabetes describ- of the DCCT and UK Prospective Dia- women) may be tested more frequently ing the correlation between A1C and betes Study (UKPDS) cohorts suggests than every 3 months. The availability of mean glucose was derived from relatively that treatment to A1C targets below or the A1C result at the time that the patient sparse data (one seven-point profile over around 7% in the years soon after the is seen (point-of-care testing) has been re- 1 day per A1C reading) in the primarily diagnosis of diabetes is associated with ported to result in increased intensifica- Caucasian type 1 participants in the Dia- long-term reduction in risk of macro- tion of therapy and improvement in betes Control and Complications Trial vascular disease. Until more evidence glycemic control (40,41). (DCCT) trial (43). Clinicians should note becomes available, the general goal of The A1C test is subject to certain lim- that the numbers in the table are now dif- 7% appears reasonable for many DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S19
  • 8. Standards of Medical Care adults for macrovascular risk reduc- rates of microvascular complications, with those previously in the standard arm tion. (B) even with loss of glycemic separation be- (55). ● Subgroup analyses of clinical trials such tween the intensive and standard cohorts The UKPDS trial of type 2 diabetes as the DCCT and UKPDS and the mi- after the end of the randomized con- observed a 16% reduction in cardiovascu- crovascular evidence from the Action in trolled (51). lar complications (combined fatal or non- Diabetes and Vascular Disease: Preterax In each of these large randomized fatal MI and sudden death) in the and Diamicron MR Controlled Evalua- prospective clinical trials, treatment regi- intensive glycemic control arm, although tion (ADVANCE) trial suggest a small mens that reduced average A1C to 7% this difference was not statistically signif- but incremental benefit in microvascu- ( 1% above the upper limits of normal) icant (P 0.052), and there was no sug- lar outcomes with A1C values closer to were associated with fewer long-term mi- gestion of benefit on other CVD outcomes normal. Therefore, for selected individ- crovascular complications; however, in- such as stroke. In an epidemiologic anal- ual patients, providers might reason- tensive control was found to increase the ysis of the study cohort, a continuous as- ably suggest even lower A1C goals than risk of severe hypoglycemia, most notably sociation was observed, such that for the general goal of 7%, if this can be in the DCCT, and led to weight gain every percentage point lower median on- achieved without significant hypogly- (39,52). study A1C (e.g., 8 to 7%) there was a sta- cemia or other adverse effects of treat- Epidemiological analyses of the tistically significant 18% reduction in ment. Such patients might include DCCT and UKPDS (39,45) demonstrate a CVD events, again with no glycemic those with short duration of diabetes, curvilinear relationship between A1C and threshold. A recent report of 10 years of long life expectancy, and no significant microvascular complications. Such anal- follow-up of the UKPDS cohort describes, CVD. (B) yses suggest that, on a population level, for the participants originally randomized ● Conversely, less stringent A1C goals to intensive glycemic control compared the greatest number of complications will than the general goal of 7% may be be averted by taking patients from very with those randomized to conventional appropriate for patients with a history poor control to fair or good control. These glycemic control, long-term reductions in of severe hypoglycemia, limited life ex- analyses also suggest that further lowering MI (15% with sulfonylurea or insulin as pectancy, advanced microvascular or of A1C from 7 to 6% is associated with initial pharmacotherapy, 33% with met- macrovascular complications, exten- further reduction in the risk of microvas- formin as initial pharmacotherapy, both sive comorbid conditions, and those cular complications, albeit the absolute statistically significant) and in all-cause with longstanding diabetes in whom mortality (13 and 27%, respectively, both risk reductions become much smaller. the general goal is difficult to attain de- statistically significant) (51). Given the substantially increased risk of spite DSME, appropriate glucose mon- Because of ongoing uncertainty re- hypoglycemia (particularly in those with itoring, and effective doses of multiple garding whether intensive glycemic con- type 1 diabetes) and the relatively much glucose-lowering agents including in- trol can reduce the increased risk of CVD greater effort required to achieve near- sulin. (C) events in people with type 2 diabetes, sev- normoglycemia, the risks of lower targets eral large long-term trials were launched Glycemic control is fundamental to the may outweigh the potential benefits on in the past decade to compare the effects management of diabetes. The DCCT, a microvascular complications on a popu- of intensive versus standard glycemic prospective, randomized, controlled trial lation level. However, selected individual control on CVD outcomes in relatively of intensive versus standard glycemic patients, especially those with little co- high-risk participants with established control in patients with relatively recently morbidity and long life expectancy (who type 2 diabetes. diagnosed type 1 diabetes, showed defin- may reap the benefits of further lowering The Action to Control Cardiovascular itively that improved glycemic control is of glycemia below 7%) may, at patient Risk in Diabetes (ACCORD) study ran- associated with significantly decreased and provider judgment, adopt glycemic domized 10,251 participants with either rates of microvascular (retinopathy and targets as close to normal as possible as history of a CVD event (ages 40 –79 years) nephropathy) as well as neuropathic long as significant hypoglycemia does not or significant CVD risk (ages 55–79) to a complications (45). Follow-up of the become a barrier. strategy of intensive glycemic control (tar- DCCT cohorts in the Epidemiology of Di- Whereas many epidemiologic studies get A1C 6.0%) or standard glycemic abetes Interventions and Complications and meta-analyses (53,54) have clearly control (A1C target 7.0 –7.9%). Investiga- (EDIC) study has shown persistence of shown a direct relationship between A1C tors used multiple glycemic medications this effect in previously intensively and CVD, the potential of intensive glyce- in both arms. ACCORD participants were treated subjects, even though their glyce- mic control to reduce CVD has been less on average 62 years old and had a mean mic control has been equivalent to that of clearly defined. In the DCCT, there was a duration of diabetes of 10 years, with 35% previous standard arm subjects during trend toward lower risk of CVD events already treated with insulin at baseline. follow-up (46,47). with intensive control (risk reduction From a baseline median A1C of 8.1%, the In type 2 diabetes, the Kumamoto 41%, 95% CI 10 – 68%), but the number intensive arm reached a median A1C of study (48) and the UKPDS (49,50) dem- of events was small. However, 9-year 6.4% within 12 months of randomiza- onstrated significant reductions in micro- post-DCCT follow-up of the cohort has tion, while the standard group reached a vascular and neuropathic complications shown that participants previously ran- median A1C of 7.5%. Other risk factors with intensive therapy. Similar to the domized to the intensive arm had a 42% were treated aggressively and equally in DCCT-EDIC findings, long-term fol- reduction (P 0.02) in CVD outcomes both groups. The intensive glycemic con- low-up of the UKPDS cohort has recently and a 57% reduction (P 0.02) in the trol group had more use of insulin in com- demonstrated a “legacy effect” of early in- risk of nonfatal myocardial infarction bination with multiple oral agents, tensive glycemic control on long-term (MI), stroke, or CVD death compared significantly more weight gain, and more S20 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 9. Position Statement episodes of severe hypoglycemia than the Intensive glycemic control significantly use of insulin, TZDs, other drugs, and standard group. reduced the primary endpoint (HR 0.90 drug combinations; and greater weight In February 2008, the glycemic con- [95% CI 0.82– 0.98]; P 0.01), although gain. Such factors may be associated sta- trol study of ACCORD was halted on the this was due to a significant reduction in tistically with the higher mortality rate in recommendation of the study’s data safety the microvascular outcome (0.86 [0.77– the intensive arm but may not be caus- monitoring board due to the finding of an 0.97], P 0.01), primarily development ative. It is biologically plausible that se- increased rate of mortality in the intensive of macroalbuminuria, with no significant vere hypoglycemia could increase the risk arm compared with the standard arm reduction in the macrovascular outcome of cardiovascular death in participants (1.41%/year vs. 1.14%/year; HR 1.22 (0.94 [0.84 –1.06]; P 0.32). There was with high underlying CVD risk. Other [95% CI 1.01–1.46]), with a similar in- no difference in overall or cardiovascular plausible mechanisms for the increase in crease in cardiovascular deaths. The pri- mortality between the intensive and the mortality in ACCORD include weight mary outcome of ACCORD (MI, stroke, standard glycemic control arms (57). gain, unmeasured drug effects or interac- or cardiovascular death) was lower in the The VADT randomized 1,791 partic- tions, or the overall “intensity” of the AC- intensive glycemic control group due to a ipants with type 2 diabetes uncontrolled CORD intervention (use of multiple oral reduction in nonfatal MI, although this on insulin or maximal dose oral agents glucose-lowering drugs along with multi- finding was not statistically significant (median entry A1C 9.4%) to a strategy of ple doses of insulin, frequent therapy ad- when the study was terminated (HR 0.90 intensive glycemic control (goal A1C justments to push A1C and self- [95% CI 0.78 –1.04]; P 0.16) (56). 6.0%) or standard glycemic control, monitored blood glucose to very low Exploratory analyses of the mortality with a planned A1C separation of at least targets, and an intense effort to aggres- findings of ACCORD (evaluating vari- 1.5%. Medication treatment algorithms sively reduce A1C by 2% in participants ables including weight gain, use of any were used to achieve the specified glyce- entering the trial with advanced diabetes specific drug or drug combination, and mic goals, with a goal of using similar and multiple comorbidities). hypoglycemia) were reportedly unable to medications in both groups. Median A1C Since the ADVANCE trial did not identify an explanation for the excess levels of 6.9 and 8.4% were achieved in show any increase in mortality in the in- mortality in the intensive arm. Prespeci- the intensive and standard arms, respec- tensive glycemic control arm, examining fied subset analyses showed that partici- tively, within the first year of the study. the differences between ADVANCE and pants with no previous CVD event and Other CVD risk factors were treated ag- ACCORD supports additional hypothe- those who had a baseline A1C 8% had a gressively and equally in both groups. ses. ADVANCE participants on average statistically significant reduction in the The primary outcome of the VADT appeared to have earlier or less advanced primary CVD outcome. was a composite of CVD events (MI, diabetes, with shorter duration by 2–3 The ADVANCE study randomized stroke, cardiovascular death, revascular- years and lower A1C at entry despite very 11,140 participants to a strategy of inten- ization, hospitalization for heart failure, little use of insulin at baseline. A1C was sive glycemic control (with primary ther- and amputation for ischemia). During a also lowered less and more gradually in apy being the sulfonylurea gliclizide and mean 6-year follow-up period, the cumu- the ADVANCE trial, and there was no sig- additional medications as needed to lative primary outcome was nonsignifi- nificant weight gain with intensive achieve a target A1C of 6.5%) or to stan- cantly lower in the intensive arm (HR glycemic therapy. Although severe hypo- dard therapy (in which any medication 0.87 [95% CI 0.73–1.04]; P 0.12). glycemia was defined somewhat differ- but gliclizide could be used and the gly- There were more CVD deaths in the in- ently in the three trials, it appears that this cemic target was according to “local tensive arm than in the standard arm (40 occurred in fewer than 3% of intensively guidelines”). ADVANCE participants vs. 33; sudden deaths 11 vs. 4), but the treated ADVANCE participants for the (who had to be at least 55 years of age difference was not statistically significant. entire study duration (median 5 years) with either known vascular disease or at Post hoc subgroup analyses suggested compared with 16% of intensively least one other vascular risk factor) were that duration of diabetes interacted with treated subjects in ACCORD and 21% in slightly older and of similar high CVD risk randomization such that participants VADT. as those in ACCORD. However, they had with duration of diabetes less than about It is likely that the increase in mortal- an average duration of diabetes 2 years 12 years appeared to have a CVD benefit ity in ACCORD was related to the overall shorter, lower baseline A1C (median of intensive glycemic control while those treatment strategies for intensifying glyce- 7.2%), and almost no use of insulin at with longer duration of disease before mic control in the study population, not enrollment. The median A1C levels study entry had a neutral or even adverse the achieved A1C per se. The ADVANCE achieved in the intensive and standard effect of intensive glycemic control. Other study achieved a median A1C in its inten- arms were 6.3 and 7.0%, respectively, exploratory analyses suggested that se- sive arm similar to that in the ACCORD and maximal separation between the vere hypoglycemia within the past 90 study, with no increased mortality haz- arms took several years to achieve. Use of days was a strong predictor of the primary ard. Thus, the ACCORD mortality find- other drugs that favorably impact CVD outcome and of CVD mortality (58). ings do not imply that patients with type 2 risk (aspirin, statins, ACE inhibitors) was The cause of the excess deaths in the diabetes who can easily achieve or main- lower in ADVANCE than in the ACCORD intensive glycemic control arm of AC- tain low A1C levels with lifestyle modifi- or Veterans Affairs Diabetes Trial (VADT). CORD compared with the standard arm cations with or without pharmacotherapy The primary outcome of ADVANCE has been difficult to pinpoint. By design of are at risk and need to “raise” their A1C. was a combination of microvascular the trial, randomization to the intensive The three trials compared treatments events (nephropathy and retinopathy) arm was associated with or led to many to A1C levels in the “flatter” part of the and major adverse cardiovascular events downstream effects, such as higher rates observational glycemia-CVD risk curves (MI, stroke, and cardiovascular death). of severe hypoglycemia; more frequent (median A1C of 6.4 – 6.9% in the inten- DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S21
  • 10. Standards of Medical Care Table 9—Summary of glycemic recommendations for non-pregnant adults with diabetes gate measures of vascular pathology, such A1C 7.0%* as endothelial dysfunction, are negatively Preprandial capillary plasma glucose 70–130 mg/dl (3.9–7.2 mmol/l) affected by postprandial hyperglycemia Peak postprandial capillary plasma glucose 180 mg/dl ( 10.0 mmol/l) (60). It is clear that postprandial hyper- Key concepts in setting glycemic goals: glycemia, like preprandial hyperglyce- ● A1C is the primary target for glycemic control. mia, contributes to elevated A1C levels, ● Goals should be individualized based on: with its relative contribution being higher ● duration of diabetes at A1C levels that are closer to 7%. How- ● age/life expectancy ever, outcome studies have clearly shown ● comorbid conditions A1C to be the primary predictor of com- ● known CVD or advanced microvascular plications, and landmark glycemic con- complications trol trials such as the DCCT and UKPDS ● hypoglycemia unawareness relied overwhelmingly on preprandial ● individual patient considerations SMBG. Additionally, a randomized con- ● More or less stringent glycemic goals may be trolled trial presented at the 68th Scien- appropriate for individual patients. tific Sessions of the American Diabetes ● Postprandial glucose may be targeted if A1C goals are Association in June 2008 found no CVD not met despite reaching preprandial glucose goals. benefit of insulin regimens targeting post- *Referenced to a nondiabetic range of 4.0 – 6.0% using a DCCT-based assay. Postprandial glucose measure- prandial glucose compared with those ments should be made 1–2 h after the beginning of the meal, generally peak levels in patients with diabetes. targeting preprandial glucose. A reason- able recommendation for postprandial testing and targets is that for individuals sive arms compared with 7.0 – 8.4% in events with intensive glycemic control in who have premeal glucose values within the standard arms). Importantly, their re- ACCORD, ADVANCE, and VADT should target but have A1C values above target, sults should not be extrapolated to imply not lead clinicians to abandon the general monitoring postprandial plasma glucose that there would be no cardiovascular target of an A1C 7.0% and thereby dis- (PPG) 1–2 h after the start of the meal and benefit of glucose lowering from very count the benefit of good control on what treatment aimed at reducing PPG values poor control (e.g., A1C 9%) to good are serious and debilitating microvascular to 180 mg/dl may help lower A1C. control (e.g., A1C 7%). complications. As noted above, less stringent treat- All three trials were carried out in par- The evidence for a cardiovascular ment goals may be appropriate for adults ticipants with established diabetes (mean benefit of intensive glycemic control pri- with limited life expectancies or advanced duration 8 –11 years) and either known marily rests on long-term follow-up of vascular disease. Glycemic goals for chil- CVD or multiple risk factors suggesting study cohorts treated early in the course dren are provided in Section VII.A.1.a. the presence of established atherosclero- of type 1 and type 2 diabetes and subset Severe or frequent hypoglycemia is an ab- sis. Subset analyses of the three trials sug- analyses of ACCORD, ADVANCE, and solute indication for the modification of gested a significant benefit of intensive VADT. Conversely, the mortality findings treatment regimens, including setting glycemic control on CVD in participants in ACCORD suggest that the potential higher glycemic goals. with shorter duration of diabetes, lower risks of very intensive glycemic control Regarding goals for glycemic control A1C at entry, and/or or absence of known may outweigh its benefits in some pa- for women with GDM, recommendations CVD. The DCCT-EDIC study and the tients, such as those with very long dura- from the Fifth International Workshop- long-term follow-up of the UKPDS cohort tion of diabetes, known history of severe Conference on Gestational Diabetes Mel- both suggest that intensive glycemic con- hypoglycemia, advanced atherosclerosis, litus (61) were to target the following trol initiated soon after diagnosis of dia- and advanced age/frailty. Certainly, pro- maternal capillary glucose concentra- betes in patients with a lower level of CVD viders should be vigilant in preventing se- tions: risk may impart long-term protection vere hypoglycemia in patients with from CVD events. As is the case with mi- advanced disease and should not aggres- crovascular complications, it may be that sively attempt to achieve near-normal ● preprandial: 95 mg/dl (5.3 mmol/l) glycemic control plays a greater role be- A1C levels in patients in whom such a and either fore macrovascular disease is well devel- target cannot be reasonably easily and ● 1-h postmeal: 140 mg/dl (7.8 mmol/l) oped and minimal or no role when it is safely achieved. or advanced. Recommended glycemic goals for ● 2-h postmeal: 120 mg/dl (6.7 mmol/l) The benefits of intensive glycemic nonpregnant adults are shown in Table 9. control on microvascular and neuro- The recommendations are based on those For women with preexisting type 1 or pathic complications are well established for A1C, with listed blood glucose levels type 2 diabetes who become pregnant, a for both type 1 and type 2 diabetes. The that appear to correlate with achievement recent consensus statement (62) recom- ADVANCE trial has added to that evi- of an A1C of 7%. The issue of pre- ver- mended the following as optimal glyce- dence base by demonstrating a significant sus postprandial SMBG targets is complex mic goals, if they can be achieved without reduction in the risk of new or worsening (59). Elevated postchallenge (2-h OGTT) excessive hypoglycemia: albuminuria when A1C was lowered to glucose values have been associated with 6.3% compared with standard glycemic increased cardiovascular risk indepen- control achieving an A1C of 7.0%. The dent of FPG in some epidemiological ● premeal, bedtime, and overnight glu- lack of significant reduction in CVD studies. In diabetic subjects, some surro- cose 60 –99 mg/dl S22 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 11. Position Statement ● peak postprandial glucose 100 –129 The algorithm took into account the dietary strategies including reduced mg/dl evidence for A1C-lowering of the individ- calories and reduced intake of dietary ● A1C 6.0% ual interventions, their additive effects, fat, can reduce the risk for developing and their expense. The precise drugs used diabetes and are therefore recom- 3. Approach to treatment and their exact sequence may not be as mended. (A) important as achieving and maintaining ● Individuals at high risk for type 2 diabetes a. Therapy for type 1 diabetes. The glycemic targets safely. Medications not should be encouraged to achieve the U.S. DCCT clearly showed that intensive insu- included in the consensus algorithm, ow- Department of Agriculture recommenda- lin therapy (three or more injections per ing to less glucose-lowering effectiveness, tion for dietary fiber (14 g fiber/1,000 day of insulin or continuous subcutane- limited clinical data, and/or relative ex- kcal) and foods containing whole grains ous insulin infusion (CSII, or insulin pense, still may be appropriate choices in (one-half of grain intake). (B) pump therapy) was a key part of im- individual patients to achieve glycemic proved glycemia and better outcomes goals. Initiation of insulin at time of diagno- Dietary fat intake in diabetes (45). At the time of the study, therapy was sis is recommended for individuals present- management carried out with short- and intermediate- ing with weight loss or other severe ● Saturated fat intake should be 7% of acting human insulins. Despite better mi- hyperglycemic symptoms or signs. For a list total calories. (A) crovascular outcomes, intensive insulin of currently approved diabetes medica- ● Intake of trans fat should be minimized. (B) therapy was associated with a marked in- tions, see http://ndep.nih.gov/diabetes/ crease in severe hypoglycemia (62 epi- pubs/Drug_tables_supplement.pdf. Carbohydrate intake in diabetes sodes per 100 patient-years of therapy). management Since the time of the DCCT, a number of D. MNT ● Monitoring carbohydrate, whether by rapid-acting and long-acting insulin ana- carbohydrate counting, exchanges, or logs have been developed. These analogs General recommendations experience-based estimation, remains a were designed to be more “physiological” ● Individuals who have pre-diabetes or key strategy in achieving glycemic con- in their pharmacokinetics and pharmaco- diabetes should receive individualized trol. (A) dynamics and are associated with less hy- MNT as needed to achieve treatment ● For individuals with diabetes, the use of poglycemia with equal A1C lowering in goals, preferably provided by a regis- the glycemic index and glycemic load type 1 diabetes (63,64). tered dietitian familiar with the compo- may provide a modest additional bene- Therefore, recommended therapy for nents of diabetes MNT. (B) fit for glycemic control over that ob- type 1 diabetes consists of the following ● MNT should be covered by insurance served when total carbohydrate is components: 1) use of multiple dose in- and other payors. (E) considered alone. (B) sulin injections (3– 4 injections per day of basal and prandial insulin) or CSII ther- Energy balance, overweight, and Other nutrition recommendations apy; 2) matching of prandial insulin to obesity ● Sugar alcohols and nonnutritive sweet- carbohydrate intake, premeal blood glu- ● In overweight and obese insulin- eners are safe when consumed within cose, and anticipated activity; and 3) for resistant individuals, modest weight the acceptable daily intake levels estab- many patients (especially if hypoglycemia loss has been shown to reduce insulin lished by the Food and Drug Adminis- is a problem), use of insulin analogs. resistance. Thus, weight loss is recom- tration (FDA). (A) There are excellent reviews available that mended for all overweight or obese in- ● If adults with diabetes choose to use alco- guide the initiation and management of dividuals who have or are at risk for hol, daily intake should be limited to a insulin therapy to achieve desired glyce- diabetes. (A) moderate amount (one drink per day or mic goals (3,63,65). ● For weight loss, either low-carbohy- less for adult women and two drinks per b. Therapy for type 2 diabetes. The ADA drate or low-fat calorie restricted diets day or less for adult men). (E) and the European Association for the may be effective in the short-term (up ● Routine supplementation with antioxi- Study of Diabetes published a consensus to 1 year). (A) dants, such as vitamins E and C and statement on the approach to manage- ● For patients on low-carbohydrate diets, carotene, is not advised because of lack ment of hyperglycemia in individuals monitor lipid profiles, renal function, of evidence of efficacy and concern re- with type 2 diabetes (66) and recently and protein intake (in those with ne- lated to long-term safety. (A) published an update (67). Highlights of phropathy) and adjust hypoglycemic ● Benefit from chromium supplementa- this approach are: intervention at the time therapy as needed. (E) tion in people with diabetes or obesity of diagnosis with metformin in combina- ● Physical activity and behavior modifica- has not been conclusively demon- tion with lifestyle changes (MNT and tion are important components of weight strated and, therefore, cannot be rec- exercise) and continuing timely augmen- loss programs and are most helpful in ommended. (E) tation of therapy with additional agents maintenance of weight loss. (B) (including early initiation of insulin ther- MNT is an integral component of diabetes apy) as a means of achieving and main- Primary prevention of diabetes prevention, management, and self- taining recommended levels of glycemic ● Among individuals at high risk for de- management education. In addition to its control (i.e., A1C 7% for most patients). veloping type 2 diabetes, structured role in preventing and controlling diabe- The overall objective is to achieve and programs that emphasize lifestyle tes, ADA recognizes the importance of maintain glycemic control and to change changes that include moderate weight nutrition as an essential component of an interventions when therapeutic goals are loss (7% body weight) and regular overall healthy lifestyle. A full review of not being met. physical activity (150 min/week), with the evidence regarding nutrition in pre- DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S23
  • 12. Standards of Medical Care venting and controlling diabetes and its (10). Look AHEAD (Action for Health in sources of energy, fiber, vitamins, and complications and additional nutrition- Diabetes) is a large clinical trial designed minerals that are important in dietary pal- related recommendations can be found in to determine whether long-term weight atability (92). the ADA position statement “Nutrition loss will improve glycemia and prevent Although numerous studies have at- Recommendations and Interventions for cardiovascular events in subjects with tempted to identify the optimal mix of Diabetes,” published in 2007 and up- type 2 diabetes. One-year results of the macronutrients for meal plans of people dated for 2008 (68). Achieving nutrition- intensive lifestyle intervention in this trial with diabetes, it is unlikely that one such related goals requires a coordinated team show an average of 8.6% weight loss, sig- combination of macronutrients exists. effort that includes the active involvement nificant reduction of A1C, and reduction The best mix of carbohydrate, protein, of the person with pre-diabetes or diabe- in several CVD risk factors (87). When and fat appears to vary depending on tes. Because of the complexity of nutrition completed, the Look AHEAD trial should individual circumstances. For those indi- issues, it is recommended that a registered provide insight into the effects of long- viduals seeking guidance as to macronu- dietitian who is knowledgeable and term weight loss on important clinical trient distribution in healthy adults, the skilled in implementing nutrition therapy outcomes. Dietary Reference Intake (DRI) system into diabetes management and education The optimal macronutrient distribu- may be helpful (92). It must be clearly be the team member who provides MNT. tion of weight loss diets has not been es- recognized that regardless of the macro- Clinical trials/outcome studies of tablished. Although low-fat diets have nutrient mix, total caloric intake must be MNT have reported decreases in A1C at traditionally been promoted for weight appropriate for the weight management 3– 6 months ranging from 0.25 to 2.9% loss, several randomized controlled trials goal. Further, individualization of the ma- with higher reductions seen in type 2 found that subjects on low-carbohydrate cronutrient composition will depend on diabetes of shorter duration. Multiple diets ( 130 g/day of carbohydrate) lost the metabolic status of the patient (e.g., studies have demonstrated sustained im- more weight at 6 months than subjects on lipid profile, renal function) and/or food provements in A1C at 12 months and low-fat diets (88,89); however, at 1 year, preferences. Individuals who choose to longer when a registered dietician pro- the difference in weight loss between the consume plant-based diets that are well vided follow-up visits ranging from low-carbohydrate and low-fat diets was planned and nutritionally adequate (i.e., monthly to three sessions per year (69 – not significant, and weight loss was mod- vegetarian) may continue, as this can be 76). Meta-analyses of studies in nondia- est with both diets. Another study of over- done without being deleterious to meta- betic, free-living subjects report that MNT weight women randomized to one of four bolic control (93,94). reduces LDL cholesterol by 15–25 mg/dl diets showed significantly more weight The primary goal with respect to di- (77) or can lower LDL cholesterol by up loss at 12 months with the Atkins low- etary fat in individuals with diabetes is to to 16% (78), while clinical trials support a carbohydrate diet than with higher- limit saturated fatty acids, trans fatty ac- role for lifestyle modification in treating carbohydrate diets (90). Changes in ids, and cholesterol intake so as to reduce hypertension (78,79). serum triglyceride and HDL cholesterol risk for CVD. Saturated and trans fatty ac- Because of the effects of obesity on were more favorable with the low- ids are the principal dietary determinants insulin resistance, weight loss is an im- carbohydrate diets. In one study, those of plasma LDL cholesterol. There is a lack portant therapeutic objective for over- subjects with type 2 diabetes demon- of evidence on the effects of specific fatty weight or obese individuals with pre- strated a greater decrease in A1C with a acids on people with diabetes, so the rec- diabetes or diabetes (80). Short-term low-carbohydrate diet than with a low-fat ommended goals are consistent with studies have demonstrated that moderate diet (89). A recent meta-analysis showed those for individuals with CVD (78,95). weight loss (5% of body weight) in sub- that at 6 months, low-carbohydrate diets The FDA has approved five nonnutri- jects with type 2 diabetes is associated were associated with greater improve- tive sweeteners for use in the U.S.: acesul- with decreased insulin resistance, im- ments in triglyceride and HDL cholesterol fame potassium, aspartame, neotame, proved measures of glycemia and lipemia, concentrations than low-fat diets; how- saccharin, and sucralose. Before being al- and reduced blood pressure (81); longer- ever, LDL cholesterol was significantly lowed on the market, all underwent rig- term studies (52 weeks) showed mixed higher on the low-carbohydrate diets orous scrutiny and were shown to be safe effects on A1C in adults with type 2 dia- (91). In a 2-year dietary intervention when consumed by the public, including betes (82– 85), and results were con- study, Mediterranean and low-carbohy- people with diabetes and women during founded by pharmacologic weight loss drate diets were found to be effective and pregnancy. Reduced calorie sweeteners therapy. A systematic review of 80 weight safe alternatives to a low-fat diet for approved by the FDA include sugar alco- loss studies of 1 year duration demon- weight reduction in moderately obese hols (polyols) such as erythritol, isomalt, strated that moderate weight loss participants (85). lactitol, maltitol, mannitol, sorbitol, xyli- achieved through diet alone, diet and ex- The recommended dietary allowance tol, tagatose, and hydrogenated starch hy- ercise, and meal replacements can be for digestible carbohydrate is 130 g/day drolysates. The use of sugar alcohols achieved and maintained over the long and is based on providing adequate glu- appears to be safe; however, they may term (4.8 – 8% weight loss at 12 months) cose as the required fuel for the central cause diarrhea, especially in children. (86). The multifactorial intensive lifestyle nervous system without reliance on glu- intervention employed in the DPP, which cose production from ingested protein or Reimbursement for MNT included reduced intake of fat and calo- fat. Although brain fuel needs can be met MNT, when delivered by a registered di- ries, led to weight loss averaging 7% at 6 on lower carbohydrate diets, long-term etitian according to nutrition practice months and maintenance of 5% weight metabolic effects of very-low-carbohy- guidelines, is reimbursed as part of the loss at 3 years, associated with a 58% re- drate diets are unclear, and such diets Medicare program as overseen by the duction in incidence of type 2 diabetes eliminate many foods that are important Centers for Medicare and Medicaid Ser- S24 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 13. Position Statement vices (CMS) (www.cms.hhs.gov/ therapy in subjects with type 2 diabetes they are first diagnosed. Ongoing DSME medicalnutritiontherapy) diagnosed less than 2 years before ran- also helps people with diabetes maintain domization and BMI 30 – 40 kg/m2 (97). effective self-management as their diabe- E. Bariatric surgery In this trial, 73% of surgically treated pa- tes presents new challenges and treatment tients achieved “remission” of their diabe- advances become available. DSME helps Recommendations tes, compared with 13% of those treated patients optimize metabolic control, pre- ● Bariatric surgery should be considered medically. The latter group lost only 1.7% vent and manage complications, and for adults with BMI 35 kg/m2 and of body weight, suggesting that their ther- maximize quality of life in a cost-effective type 2 diabetes, especially if the diabe- apy was not optimal. Overall, the trial had manner (108). tes is difficult to control with lifestyle 60 subjects, and only 13 had a BMI under Since the 1990s, there has been a shift and pharmacologic therapy. (B) 35 kg/m2, making it difficult to generalize from a didactic approach, with DSME fo- ● Patients with type 2 diabetes who have these results widely to diabetic patients cusing on providing information, to a undergone bariatric surgery need life- who are less severely obese or with longer skill-based approach that focuses on long lifestyle support and medical duration of diabetes. helping those with diabetes make in- monitoring. (E) Bariatric surgery is costly in the short formed self-management choices. Care of ● Although small trials have shown glyce- term and has some risks. Rates of morbid- diabetes has shifted to an approach that is mic benefit of bariatric surgery in patients ity and mortality directly related to the more patient centered and that places the with type 2 diabetes and BMI of 30 –35 surgery have been reduced considerably person with diabetes, and joint decision- kg/m2, there is currently insufficient evi- in recent years, with 30-day mortality making with heath care professionals, at dence to generally recommend surgery in rates now 0.28%, similar to those of lapa- the center of the care model. Patient- patients with BMI 35 kg/m2 outside of a roscopic cholecystectomy (98). Longer- centered care is respectful of and respon- research protocol. (E) term concerns include vitamin and sive to individual patient preferences, ● The long-term benefits, cost- mineral deficiencies, osteoporosis, and needs, and values and ensures that patient effectiveness, and risks of bariatric sur- rare but often severe hypoglycemia from values guide all decision making (109). gery in individuals with type 2 diabetes insulin hypersecretion. Cohort studies at- should be studied in well-designed ran- tempting to match subjects suggest that domized controlled trials with optimal the procedure may reduce longer-term Evidence for the benefits of DSME medical and lifestyle therapy as the mortality rates (99), and it is reasonable to Several studies have found that DSME is comparator. (E) postulate that there may be recouping of associated with improved diabetes costs over the long run. However, studies knowledge and improved self-care behav- Gastric reduction surgery, either gastric of the mechanisms of glycemic improve- ior (101), improved clinical outcomes banding or procedures that involve by- ment, long-term benefits and risks, and such as lower A1C (102,103,105,106, passing or transposing sections of the cost-effectiveness of bariatric surgery in 110), lower self-reported weight (101), small intestine, when part of a compre- individuals with type 2 diabetes will re- hensive team approach, can be an effec- quire well-designed randomized clinical and improved quality of life (104). Better tive weight loss treatment for severe trials, with optimal medical and lifestyle outcomes were reported for DSME inter- obesity, and national guidelines support therapy of diabetes and cardiovascular ventions that were longer and included its consideration for people with type 2 risk factors as the comparitor. follow-up support (101), that were tai- diabetes who have BMI at or exceeding 35 lored to individual needs and preferences kg/m2. Bariatric surgery has been shown F. DSME (100), and that addressed psychosocial is- to lead to near or complete normalization sues (100,101,105). Both individual and of glycemia in 55–95% of patients with Recommendations group approaches have been found effec- type 2 diabetes, depending on the surgical ● People with diabetes should receive tive ((111,112). There is increasing evi- procedure. A meta-analysis of studies of DSME according to national standards dence for the role of a community health bariatric surgery reported that 78% of when their diabetes is diagnosed and as worker in delivering diabetes education individuals with type 2 diabetes had com- needed thereafter. (B) in addition to the core team (113). plete “resolution” of diabetes (normaliza- ● Self-management behavior change is tion of blood glucose levels in the absence the key outcome of DSME and should of medications), and that the resolution be measured and monitored as part of National standards for DSME rates were sustained in studies that had care. (E) ADA-recognized DSME programs have follow-up exceeding 2 years (96). Resolu- ● DSME should address psychosocial is- staff that must be certified diabetes edu- tion rates are lowest with procedures that sues, since emotional well-being is cators or have recent experience in diabe- only constrict the stomach and higher strongly associated with positive diabe- tes education and management. The with those that bypass portions of the tes outcomes. (C) curriculum of ADA-recognized DSME small intestine. Additionally, there is in- ● DSME should be reimbursed by third- programs must cover all nine areas of di- creasing evidence that intestinal bypass party payors. (E) abetes management, with the assessed procedures may have glycemic effects that needs of the individual determining are independent of, and additive to, their DSME is an essential element of diabetes which areas are addressed. The ADA Ed- effects on weight. care (100 –106), and National Standards ucation Recognition Program (ERP) is a A recent randomized controlled trial for DSME (107) are based on evidence for mechanism to ensure diabetes education compared adjustable gastric banding to its benefits. Education helps people with programs meet the national standards and “best available” medical and lifestyle diabetes initiate effective self-care when provide quality diabetes care. DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S25
  • 14. Standards of Medical Care Reimbursement for DSME older adults with type 2 diabetes Exercise in the presence of specific DSME, when provided by a program that (120,121) and for an additive benefit of long-term complications of diabetes meets ADA ERP standards, is reimbursed combined aerobic and resistance exercise Retinopathy. In the presence of prolifer- as part of the Medicare program as over- in adults with type 2 diabetes (122). ative diabetic retinopathy (PDR) or severe seen by the Centers for Medicare and nonproliferative diabetic retinopathy Medicaid Services (CMS) (www.cms.hhs. (NPDR), vigorous aerobic or resistance gov/DiabetesSelfManagement). Evaluation of the diabetic patient exercise may be contraindicated because before recommending an exercise of the risk of triggering vitreous hemor- G. Physical activity program rhage or retinal detachment (127). Prior guidelines suggested that before rec- Peripheral neuropathy. Decreased pain Recommendations ommending a program of physical activ- sensation in the extremities results in in- ● People with diabetes should be advised ity, the provider should assess patients creased risk of skin breakdown and infec- to perform at least 150 min/week of with multiple cardiovascular risk factors tion and of Charcot joint destruction. moderate-intensity aerobic physical ac- for coronary artery disease (CAD). As dis- Therefore, in the presence of severe pe- tivity (50 –70% of maximum heart cussed more fully in Section VI.A.5, the ripheral neuropathy, it may be best to en- rate). (A) area of screening asymptomatic diabetic courage non–weight-bearing activities ● In the absence of contraindications, such as swimming, bicycling, or arm ex- patients for CAD remains unclear, and a people with type 2 diabetes should be recent ADA consensus statement on this ercises (128,129). encouraged to perform resistance train- issue concluded that routine screening is Autonomic neuropathy. Autonomic ing three times per week. (A) not recommended (123). Providers neuropathy can increase the risk of exer- should use clinical judgment in this area. cise-induced injury or adverse events ADA technical reviews on exercise in pa- Certainly, high-risk patients should be through decreased cardiac responsiveness tients with diabetes have summarized the encouraged to start with short periods of to exercise, postural hypotension, impaired value of exercise in the diabetes manage- low-intensity exercise and increase the in- thermoregulation, impaired night vision ment plan (114,115). Regular exercise tensity and duration slowly. due to impaired papillary reaction, and un- has been shown to improve blood glucose Providers should assess patients for predictable carbohydrate delivery from gas- control, reduce cardiovascular risk fac- conditions that might contraindicate cer- troparesis predisposing to hypoglycemia tors, contribute to weight loss, and im- (128). Autonomic neuropathy is also tain types of exercise or predispose to in- prove well being. Furthermore, regular strongly associated with CVD in people jury, such as uncontrolled hypertension, exercise may prevent type 2 diabetes in with diabetes (130,131). People with dia- severe autonomic neuropathy, severe pe- high-risk individuals (10 –12). Struc- betic autonomic neuropathy should un- ripheral neuropathy or history of foot le- tured exercise interventions of at least 8 dergo cardiac investigation before sions, and advanced retinopathy. The weeks’ duration have been shown to beginning physical activity more intense patient’s age and previous physical activ- lower A1C by an average of 0.66% in peo- than that to which they are accustomed. ple with type 2 diabetes, even with no ity level should be considered. Albuminuria and nephropathy. Physical significant change in BMI (116). Higher activity can acutely increase urinary pro- levels of exercise intensity are associated tein excretion. However, there is no evi- with greater improvements in A1C and in Exercise in the presence of dence that vigorous exercise increases the fitness (117). nonoptimal glycemic control rate of progression of diabetic kidney dis- Hyperglycemia. When people with type ease and likely no need for any specific Frequency and type of exercise 1 diabetes are deprived of insulin for exercise restrictions for people with dia- The U.S. Surgeon General’s report (118) 12– 48 h and are ketotic, exercise can betic kidney disease (132). recommended that most adults accumu- worsen hyperglycemia and ketosis (124); late at least 30 min of moderate-intensity therefore, vigorous activity should be avoided in the presence of ketosis. How- H. Psychosocial assessment and care activity on most, ideally all, days of the week. The studies included in the meta- ever, it is not necessary to postpone exer- analysis of effects of exercise interventions cise based simply on hyperglycemia, Recommendations on glycemic control (116) had a mean provided the patient feels well and urine ● Assessment of psychological and social number of sessions per week of 3.4, with and/or blood ketones are negative. situation should be included as an on- a mean of 49 min per session. The DPP Hypoglycemia. In individuals taking in- going part of the medical management lifestyle intervention, which included 150 sulin and/or insulin secretagogues, phys- of diabetes. (E) min per week of moderate intensity exer- ical activity can cause hypoglycemia if ● Psychosocial screening and follow-up cise, had a beneficial effect on glycemia in medication dose or carbohydrate con- should include, but is not limited to, those with pre-diabetes. Therefore, it sumption is not altered. For individuals attitudes about the illness, expectations seems reasonable to recommend 150 on these therapies, added carbohydrate for medical management and out- min of exercise per week for people with should be ingested if pre-exercise glucose comes, affect/mood, general and diabe- diabetes. levels are 100 mg/dl (5.6 mmol/l) tes-related quality of life, resources Resistance exercise improves insulin (125,126). Hypoglycemia is rare in dia- (financial, social, and emotional), and sensitivity to about the same extent as aer- betic individuals who are not treated with psychiatric history. (E) obic exercise (119). Clinical trials have insulin or insulin secretagogues, and no ● Screen for psychosocial problems such provided strong evidence for the A1C- preventive measures for hypoglycemia as depression, anxiety, eating disor- lowering value of resistance training in are usually advised in these cases. ders, and cognitive impairment when S26 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 15. Position Statement adherence to the medical regimen is ment (Table 9). Re-thinking the treatment Once SMBG glucose returns to normal, poor. (E) regimen may require assessment of barri- the individual should consume a meal ers to adherence including income, edu- or snack to prevent recurrence of hypo- Psychological and social problems can im- cational attainment, and competing glycemia. (E) pair the individual’s (133–138) or family’s demands, including those related to fam- ● Glucagon should be prescribed for all (139) ability to carry out diabetes care tasks ily responsibilities and family dynamics. individuals at significant risk of severe and therefore compromise health status. Other strategies may include culturally hypoglycemia, and caregivers or family There are opportunities for the clinician to appropriate and enhanced DSME, co- members of these individuals should be assess psychosocial status in a timely and management with a diabetes team, refer- instructed in its administration. Gluca- efficient manner so that referral for appro- ral to a medical social worker for gon administration is not limited to priate services can be accomplished. assistance with insurance coverage or health care professionals. (E) Key opportunities for screening of change in pharmacological therapy. Initi- ● Individuals with hypoglycemia un- psychosocial status occur at diagnosis, ation of or increase in SMBG, utilization awareness or one or more episodes of during regularly scheduled management of continuous glucose monitoring, fre- severe hypoglycemia should be advised visits, during hospitalizations, at discov- quent contact with the patient, or referral to raise their glycemic targets to strictly ery of complications, or when problems to an endocrinologist may be useful. avoid further hypoglycemia for at least with glucose control, quality of life, or ad- several weeks to partially reverse hypo- herence are identified (140). Patients are J. Intercurrent illness glycemia unawareness and reduce risk likely to exhibit psychological vulnerabil- The stress of illness, trauma, and/or sur- of future episodes. (B) ity at diagnosis and when their medical gery frequently aggravates glycemic con- status changes, i.e., the end of the honey- trol and may precipitate diabetic Hypoglycemia is the leading limiting fac- moon period, when the need for intensi- ketoacidosis (DKA) or nonketotic hyper- tor in the glycemic management of type 1 fied treatment is evident, and when osmolar state, life-threatening conditions and insulin-treated type 2 diabetes (146). complications are discovered (135,137). that require immediate medical care to Treatment of hypoglycemia (plasma glu- Issues known to impact self- prevent complications and death (145). cose 70 mg/dl) requires ingestion of management and health outcomes in- Any condition leading to deterioration in glucose- or carbohydrate-containing clude but are not limited to attitudes glycemic control necessitates more fre- foods. The acute glycemic response cor- about the illness, expectations for medical quent monitoring of blood glucose and relates better with the glucose content management and outcomes, affect/mood, (in ketosis-prone patients) urine or blood than with the carbohydrate content of the general and diabetes-related quality of ketones. Marked hyperglycemia requires food. Although pure glucose is the pre- life, resources (financial, social, and emo- temporary adjustment of the treatment ferred treatment, any form of carbohy- tional) (136), and psychiatric history program and, if accompanied by ketosis, drate that contains glucose will raise (137,140,141). Screening tools are avail- vomiting, or alteration in level of con- blood glucose. Added fat may retard and able for a number of these areas (142). sciousness, immediate interaction with then prolong the acute glycemic response Indications for referral to a mental health the diabetes care team. The patient treated (147). Ongoing activity of insulin or in- specialist familiar with diabetes manage- with noninsulin therapies or MNT alone sulin secretagogues may lead to recur- ment may include gross noncompliance may temporarily require insulin. Ade- rence of hypoglycemia unless further with medical regimen (by self or others) quate fluid and caloric intake must be as- food is ingested after recovery. (141), depression with the possibility of sured. Infection or dehydration are more Severe hypoglycemia (where the indi- self-harm (134,143), debilitating anxiety likely to necessitate hospitalization of the vidual requires the assistance of another (alone or with depression), indications of person with diabetes than the person person and cannot be treated with oral an eating disorder (144), or cognitive without diabetes. carbohydrate due to confusion or uncon- functioning that significantly impairs The hospitalized patient should be sciousness) should be treated using emer- judgment (143). It is preferable to incor- treated by a physician with expertise in the gency glucagon kits, which require a porate psychological assessment and management of diabetes. For further infor- prescription. Those in close contact with, treatment into routine care rather than mation on management of patients with hy- or having custodial care of, people with waiting for identification of a specific perglycemia in the hospital, see Section hypoglycemia-prone diabetes (family problem or deterioration in psychological VIII.A. For further information on manage- members, roommates, school personnel, status (142). Although the clinician may ment of DKA or nonketotic hyperosmolar child care providers, correctional institu- not feel qualified to treat psychological state, refer to the ADA position statement on tion staff, or coworkers) should be in- problems, utilizing the patient-provider hyperglycemic crises (145). structed in use of such kits. An individual relationship as a foundation for further does not need to be a health care profes- treatment can increase the likelihood that K. Hypoglycemia sional to safely administer glucagon. Care the patient will accept referral for other should be taken to ensure that unexpired services. It is important to establish that Recommendations glucagon kits are available. emotional well-being is part of diabetes ● Glucose (15–20 g) is the preferred Prevention of hypoglycemia is a crit- management (140). treatment for the conscious individual ical component of diabetes management. with hypoglycemia, although any form Teaching people with diabetes to balance I. When treatment goals are not met of carbohydrate that contains glucose insulin use, carbohydrate intake, and ex- For a variety of reasons, some people with may be used. If SMBG 15 min after ercise is a necessary but not always suffi- diabetes and their health care providers treatment shows continued hypoglyce- cient strategy. In type 1 diabetes and do not achieve the desired goals of treat- mia, the treatment should be repeated. severely insulin-deficient type 2 diabetes, DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S27
  • 16. Standards of Medical Care the syndrome of hypoglycemia unaware- as 79% during flu epidemics (151). There Goals ness, or hypoglycemia-associated auto- is sufficient evidence to support that peo- nomic failure, can severely compromise ple with diabetes have appropriate sero- ● Patients with diabetes should be treated stringent diabetes control and quality of logic and clinical responses to these to a systolic blood pressure 130 life. The deficient counter-regulatory hor- vaccinations. The Centers for Disease mmHg. (C) mone release and autonomic responses in Control and Prevention’s Advisory Com- ● Patients with diabetes should be treated this syndrome are both risk factors for, mittee on Immunization Practices recom- to a diastolic blood pressure 80 and caused by, hypoglycemia. A corollary mends influenza and pneumococcal mmHg. (B) to this “vicious cycle” is that several weeks vaccines for all individuals with diabetes of avoidance of hypoglycemia has been (http://www.cdc.gov/vaccines/recs/). For Treatment demonstrated to improve counter- a complete discussion on the prevention ● Patients with a systolic blood pressure regulation and awareness to some extent of influenza and pneumococcal disease in of 130 –139 mmHg or a diastolic blood in many patients (146,148,149). Hence, people with diabetes, consult the techni- pressure of 80 – 89 mmHg may be given patients with one or more episodes of se- cal review and position statement on this lifestyle therapy alone for a maximum vere hypoglycemia may benefit from at subject (150,153). of 3 months and then, if targets are not least short-term relaxation of glycemic achieved, be treated with the addition targets. of pharmacological agents. (E) VI. PREVENTION AND ● Patients with more severe hyperten- L. Immunization MANAGEMENT OF sion (systolic blood pressure 140 DIABETES COMPLICATIONS mmHg or diastolic blood pressure Recommendations 90 mmHg) at diagnosis or fol- ● Annually provide an influenza vaccine to A. CVD low-up should receive pharmacologic all diabetic patients 6 months of age. CVD is the major cause of morbidity and therapy in addition to lifestyle ther- (C) mortality for individuals with diabetes apy. (A) ● Administer pneumococcal polysaccha- and the largest contributor to the direct ● Pharmacologic therapy for patients ride vaccine to all diabetic patients 2 and indirect costs of diabetes. The com- with diabetes and hypertension should years of age. A one-time revaccination is mon conditions coexisting with type 2 be with a regimen that includes either recommended for individuals 64 diabetes (e.g., hypertension and dyslipi- an ACE inhibitor or an angiotensin re- years of age previously immunized demia) are clear risk factors for CVD, and ceptor blocker (ARB). If one class is not when they were 65 years of age if the diabetes itself confers independent risk. tolerated, the other should be substi- vaccine was administered 5 years Numerous studies have shown the effi- tuted. If needed to achieve blood pres- ago. Other indications for repeat vacci- cacy of controlling individual cardiovas- sure targets, a thiazide diuretic should nation include nephrotic syndrome, cular risk factors in preventing or slowing be added to those with an estimated chronic renal disease, and other immu- CVD in people with diabetes. Large ben- GFR (see below) 30 ml/min per 1.73 nocompromised states, such as after efits are seen when multiple risk factors m2 and a loop diuretic for those with an transplantation. (C) are addressed globally (154). Evidence is estimated GFR 30 ml/min per 1.73 summarized in the following sections and m2. (C) Influenza and pneumonia are common, reviewed in detail in the ADA technical ● Multiple drug therapy (two or more preventable infectious diseases associated reviews on hypertension (155), dyslipide- agents at maximal doses) is generally re- with high mortality and morbidity in the mia (156), aspirin therapy (157), and quired to achieve blood pressure targets. elderly and in people with chronic dis- smoking cessation (158) and in the Amer- (B) eases. Though there are limited studies ican Heart Association (AHA)/ADA scien- ● If ACE inhibitors, ARBs, or diuretics are reporting the morbidity and mortality of tific statement on prevention of CVD in used, kidney function and serum potas- influenza and pneumococcal pneumonia people with diabetes (159). sium levels should be closely moni- specifically in people with diabetes, ob- tored. (E) servational studies of patients with a vari- ● In pregnant patients with diabetes and ety of chronic illnesses, including 1. Hypertension/blood pressure chronic hypertension, blood pressure diabetes, show that these conditions are control target goals of 110 –129/65–79 mmHg associated with an increase in hospitaliza- are suggested in the interest of long- tions for influenza and its complications. term maternal health and minimizing Recommendations People with diabetes may be at increased impaired fetal growth. ACE inhibitors risk of the bacteremic form of pneumo- Screening and diagnosis and ARBs are contraindicated during coccal infection and have been reported ● Blood pressure should be measured at pregnancy. (E) to have a high risk of nosocomial bactere- every routine diabetes visit. Patients mia, which has a mortality rate as high as found to have a systolic blood pres- Hypertension is a common comorbidity 50% (150). sure of 130 mmHg or a diastolic of diabetes, affecting the majority of pa- Safe and effective vaccines are avail- blood pressure of 80 mmHg should tients, with prevalence depending on type able that can greatly reduce the risk of have blood pressure confirmed on a of diabetes, age, obesity, and ethnicity. serious complications from these diseases separate day. Repeat systolic blood Hypertension is a major risk factor for (151,152). In a case-control series, influ- pressure of 130 mmHg or diastolic both CVD and microvascular complica- enza vaccine was shown to reduce diabe- blood pressure of 80 mmHg con- tions. In type 1 diabetes, hypertension is tes-related hospital admission by as much firms a diagnosis of hypertension. (C) often the result of underlying nephropa- S28 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 17. Position Statement thy, while in type 2 it usually coexists als have shown anti-hypertensive effects pressure arm of the ADVANCE trial dem- with other cardiometabolic risk factors. similar to pharmacologic monotherapy of onstrated that routine administration of a reducing sodium intake and excess body fixed combination of the ACE inhibitor Screening and diagnosis weight; increasing consumption of fruits, perindopril and the diuretic indapamide Measurement of blood pressure in the of- vegetables, and low-fat dairy products; significantly reduced combined micro- fice should be done by a trained individ- avoiding excessive alcohol consumption; vascular and macrovascular outcomes, as ual and follow the guidelines established and increasing activity levels (160,168). well as CVD and total mortality. The im- for nondiabetic individuals: measure- These nonpharmacological strategies may proved outcomes could also have been ment in the seated position, with feet on also positively affect glycemia and lipid due to lower achieved blood pressure in the floor and arm supported at heart level, control. Their effects on cardiovascular the perindopril-indapamide arm (183). after 5 min of rest. Cuff size should be events have not been established. An ini- The compelling benefits of RAS inhibitors appropriate for the upper arm circumfer- tial trial of nonpharmacologic therapy in diabetic patients with albuminuria or ence. Elevated values should be con- may be reasonable in diabetic individuals renal insufficiency provide additional ra- firmed on a separate day. Because of the with mild hypertension (systolic blood tionale for use of these agents (see section clear synergistic risks of hypertension and pressure 130 –139 mmHg or diastolic VI.B below). diabetes, the diagnostic cutoff for a diag- blood pressure 80 – 89 mmHg). If the An important caveat is that most pa- nosis of hypertension is lower in people blood pressure is 140 mmHg systolic tients with hypertension require multi- with diabetes (blood pressure 130/80) and/or 90 mmHg diastolic at the time of drug therapy to reach treatment goals, than in those without diabetes (blood diagnosis, pharmacologic therapy should especially diabetic patients whose targets pressure 140/90 mmHg) (160). be initiated along with nonpharmacologic are lower. Many patients will require Home blood pressure self-monitoring therapy (160). three or more drugs to reach target goals and 24-h ambulatory blood pressure Lowering of blood pressure with reg- (160). If blood pressure is refractory to monitoring may provide additional evi- imens based on a variety of antihyperten- multiple agents, clinicians should con- dence of “white coat” and masked hyper- sive drugs, including ACE inhibitors, sider an evaluation for secondary forms of tension and other discrepancies between ARBs, -blockers, diuretics, and calcium hypertension. office and “true” blood pressure, and channel blockers, has been shown to be During pregnancy in diabetic women studies in nondiabetic populations show effective in reducing cardiovascular with chronic hypertension, target blood that home measurements may better events. Several studies have suggested pressure goals of systolic blood pressure correlate with CVD risk than office mea- that ACE inhibitors may be superior to 110 –129 mmHg and diastolic blood surements (161,162). However, the pre- dihydropyridine calcium channel block- pressure 65–79 mmHg are reasonable, as ponderance of the clear evidence of ers in reducing cardiovascular events they contribute to long-term maternal benefits of treatment of hypertension in (169 –171). However, a variety of other health. Lower blood pressure levels may people with diabetes is based on office studies have shown no specific advantage be associated with impaired fetal growth. measurements. to ACE inhibitors as initial treatment of During pregnancy, treatment with ACE hypertension in the general hypertensive inhibitors and ARBs is contraindicated, Treatment goals population, but rather an advantage on since they are likely to cause fetal damage. Randomized clinical trials have demon- cardiovascular outcomes of initial therapy Antihypertensive drugs known to be ef- strated the benefit (reduction of CHD with low-dose thiazide diuretics (160, fective and safe in pregnancy include events, stroke, and nephropathy) of low- 172,173). methyldopa, labetalol, diltiazem, ering blood pressure to 140 mmHg sys- In people with diabetes, inhibitors of clonidine, and prazosin. Chronic diuretic tolic and 80 mmHg diastolic in the renin-angiotensin system (RAS) may use during pregnancy has been associated individuals with diabetes (160,163–165). have unique advantages for initial or early with restricted maternal plasma volume, Epidemiologic analyses show that blood therapy of hypertension. In a nonhyper- which might reduce uteroplacental perfu- pressure 115/75 mmHg is associated tension trial of high-risk individuals, in- sion (184). with increased cardiovascular event rates cluding a large subset with diabetes, an and mortality in individuals with diabetes ACE inhibitor reduced CVD outcomes 2. Dyslipidemia/lipid management (160,166,167). Therefore, a target blood (174). In patients with congestive heart Recommendations pressure goal of 130/80 mmHg is rea- failure (CHF), including diabetic sub- sonable if it can be safely achieved. The groups, ARBs have been shown to reduce Screening ongoing ACCORD trial is designed to de- major CVD outcomes (175–178), and in ● In most adult patients, measure fasting termine whether blood pressure lowering type 2 patients with significant nephrop- lipid profile at least annually. In adults to systolic blood pressure 120 mmHg athy, ARBs were superior to calcium with low-risk lipid values (LDL choles- provides greater cardiovascular protec- channel blockers for reducing heart fail- terol 100 mg/dl, HDL cholesterol tion than a systolic blood pressure level of ure (179 –181). Though evidence for dis- 50 mg/dl, and triglycerides 150 140 mmHg in patients with type 2 dia- tinct advantages of RAS inhibitors on mg/dl), lipid assessments may be re- betes (www.accord.org). CVD outcomes in diabetes remains con- peated every 2 years. (E) flicting (163,182), the high CVD risks as- Treatment strategies sociated with diabetes, and the high Treatment recommendations and goals Although there are no well-controlled prevalence of undiagnosed CVD, may still ● Lifestyle modification focusing on the studies of diet and exercise in the treat- favor recommendations for their use as reduction of saturated fat, trans fat, and ment of hypertension in individuals with first-line hypertension therapy in people cholesterol intake; weight loss (if indi- diabetes, studies in nondiabetic individu- with diabetes (160). Recently, the blood cated); and increased physical activity DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S29
  • 18. Standards of Medical Care 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) Relative risk Absolute risk CVD Risk reduction reduction reduction LDL cholesterol Study (ref.) prevention Statin dose and comparator (%) (%) (%) reduction 4S-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 CVD risk of the control group and the absolute risk reduction with statin therapy is highly significant (P 0.0007). Analyses provided by Craig Williams, Pharm.D., Oregon Health & Science University, 2007. should be recommended to improve mg/dl (1.0 mmol/l) in men and 50 events CHD deaths in diabetic popula- the lipid profile in patients with diabe- mg/dl (1.3 mmol/l) in women are desir- tions. As shown in Table 10, and similar tes. (A) able. However, LDL cholesterol– to findings in nondiabetic subjects, re- ● Statin therapy should be added to life- targeted statin therapy remains the duction in “hard” CVD outcomes (CHD style therapy, regardless of baseline preferred strategy. (C) death and nonfatal MI) can be more lipid levels, for diabetic patients: ● If targets are not reached on maximally clearly seen in diabetic subjects with high ● with overt CVD (A) tolerated doses of statins, combination baseline CVD risk (known CVD and/or ● without CVD who are over the age of therapy using statins and other lipid- very high LDL cholesterol levels), but 40 and have one or more other CVD lowering agents may be considered to overall the benefits of statin therapy in risk factors. (A) achieve lipid targets but has not been people with diabetes at moderate or high ● For lower-risk patients than the above risk for CVD are convincing. evaluated in outcome studies for either (e.g., without overt CVD and under the CVD outcomes or safety. (E) Low levels of HDL cholesterol, often age of 40), statin therapy should be ● Statin therapy is contraindicated in associated with elevated triglyceride lev- considered in addition to lifestyle ther- pregnancy. (E) els, are the most prevalent pattern of dys- apy if LDL cholesterol remains above lipidemia in persons with type 2 diabetes. 100 mg/dl or in those with multiple However, the evidence base for drugs that CVD risk factors. (E) Evidence for benefits of lipid- target these lipid fractions is significantly ● In individuals without overt CVD, the lowering therapy less robust than that for statin therapy primary goal is an LDL cholesterol Patients with type 2 diabetes have an in- (193). Nicotinic acid has been shown to 100 mg/dl (2.6 mmol/l). (A) creased prevalence of lipid abnormalities, reduce CVD outcomes (194), although ● In individuals with overt CVD, a lower contributing to their high risk of CVD. the study was done in a nondiabetic co- LDL cholesterol goal of 70 mg/dl (1.8 For the past decade or more, multiple hort. Gemfibrozil has been shown to de- mmol/l), using a high dose of a statin, is clinical trials demonstrated significant ef- crease rates of CVD events in subjects an option. (B) fects of pharmacologic (primarily statin) without diabetes (195,196) and in the di- ● If drug-treated patients do not reach the therapy on CVD outcomes in subjects abetic subgroup in one of the larger trials above targets on maximal tolerated sta- with CHD and for primary CVD preven- (195). However, in a large trial specific to tin therapy, a reduction in LDL choles- tion (185). Subanalyses of diabetic sub- diabetic patients, fenofibrate failed to re- terol of 30 – 40% from baseline is an groups of larger trials (186 –190) and duce overall cardiovascular outcomes alternative therapeutic goal. (A) trials specifically in subjects with diabetes (197). ● Triglycerides levels 150 mg/dl (1.7 (191,192) showed significant primary mmol/l) and HDL cholesterol 40 and secondary prevention of CVD Dyslipidemia treatment and target lipid levels Table 11—Summary of recommendations for glycemic, blood pressure, and lipid control for For most patients with diabetes, the first adults with diabetes priority of dyslipidemia therapy (unless A1C 7.0%* severe hypertriglyceridemia is the imme- Blood pressure 130/80 mmHg diate issue) is to lower LDL cholesterol to Lipids a target goal of 100 mg/dl (2.60 mmol/l) LDL cholesterol 100 mg/dl ( 2.6 mmol/l)† (198). Lifestyle intervention, including *Referenced to a nondiabetic range of 4.0 – 6.0% using a DCCT-based assay. †In individuals with overt CVD, MNT, increased physical activity, weight a lower LDL cholesterol goal of 70 mg/dl (1.8 mmol/l), using a high dose of a statin, is an option. loss, and smoking cessation, may allow S30 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 19. Position Statement some patients to reach lipid goals. Nutri- Recent clinical trials in high-risk pa- myolysis. The risk of rhabdomyolysis is tion intervention should be tailored ac- tients, such as those with acute coronary higher with higher doses of statins and cording to each patient’s age, type of syndromes or previous cardiovascular with renal insufficiency and seems to be diabetes, pharmacological treatment, events (200 –202), have demonstrated lower when statins are combined with fe- lipid levels, and other medical conditions that more aggressive therapy with high nofibrate than gemfibrozil (207). Several and should focus on the reduction of sat- doses of statins to achieve an LDL choles- ongoing trials may provide much-needed urated fat, cholesterol, and trans unsatur- terol of 70 mg/dl led to a significant re- evidence for the effects of combination ated fat intake. Glycemic control can also duction in further events. Therefore, a therapy on cardiovascular outcomes. beneficially modify plasma lipid levels, reduction in LDL cholesterol to a goal of In 2008, a consensus panel convened particularly in patients with very high 70 mg/dl is an option in very-high-risk by ADA and the American College of Car- triglycerides and poor glycemic control. diabetic patients with overt CVD (203). diology recommended a greater focus on In those with clinical CVD or over age In individual patients, LDL choles- non-HDL cholesterol and apolipoprotein 40 with other CVD risk factors, pharma- terol lowering with statins is highly vari- B (apo B) in patients who are likely to have cological treatment should be added to able, and this variable response is poorly small LDL particles, such as people with lifestyle therapy regardless of baseline understood (204). Reduction of CVD diabetes (208). The consensus panel sug- lipid levels. Statins are the drugs of choice events with statins correlates very closely gested that for statin-treated patients in for LDL cholesterol lowering. with LDL cholesterol lowering (185). whom the LDL cholesterol goal would be In patients other than those described When maximally tolerated doses of st- 70 mg/dl (non-HDL cholesterol 100 above, statin treatment should be consid- atins fail to significantly lower LDL cho- mg/dl), apo B should be measured and ered if there is an inadequate LDL choles- lesterol ( 30% reduction from patients treated to 80 mg/dl. For patients on st- terol response to lifestyle modifications baseline), the primary aim of combination atins with an LDL cholesterol goal of and improved glucose control, or if the therapy should be to achieve additional 100 mg/dl (non-HDL cholesterol 130 patient has increased cardiovascular risk LDL cholesterol lowering. Niacin, fenofi- mg/dl), apo B should be measured and (e.g., multiple cardiovascular risk factors brate, ezetimibe, and bile acid seques- treated to below 90 mg/dl. or long duration of diabetes). Very little trants all offer additional LDL cholesterol Table 11 summarizes the general rec- clinical trial evidence exists for type 2 pa- lowering. The evidence that combination ommendations for glycemic, blood pres- tients under the age of 40, or for type 1 therapy provides a significant increment sure, and lipid control for adults with patients of any age. In the Heart Protec- in CVD risk reduction over statin therapy diabetes. tion Study, the subgroup of 600 patients alone is still elusive. with type 1 diabetes (lower age limit 40 3. Antiplatelet agents years) had a proportionately similar Treatment of other lipoprotein reduction in risk as patients with type 2 fractions or targets Recommendations diabetes, although not statistically signif- Severe hypertriglyceridemia may warrant ● Use aspirin therapy (75–162 mg/day) icant (187). Although the data are not de- immediate therapy of this abnormality as a primary prevention strategy in finitive, consideration should be given to with lifestyle and usually pharmacologic those with type 1 or type 2 diabetes at similar lipid-lowering goals in type 1 dia- therapy (fibric acid derivative or niacin) increased cardiovascular risk, includ- betic patients as those in type 2 diabetic to reduce the risk of acute pancreatitis. In ing those who are 40 years of age or patients, particularly if they have other the absence of severe hypertriglyceride- who have additional risk factors (family cardiovascular risk factors. mia, therapy targeting HDL cholesterol or history of CVD, hypertension, smok- triglycerides has intuitive appeal but lacks ing, dyslipidemia, or albuminuria). (C) Alternative LDL cholesterol goals the evidence base of statin therapy (162). ● Use aspirin therapy (75–162 mg/day) Virtually all trials of statins and CVD out- If the HDL cholesterol is 40 mg/dl and as a secondary prevention strategy in comes have tested specific doses of statins the LDL cholesterol is between 100 and those with diabetes with a history of against placebo, other doses of statin, or 129 mg/dl, gemfibrozil or niacin might be CVD. (A) other statins, rather than aiming for spe- used, especially if a patient is intolerant to ● For patients with CVD and docu- cific LDL cholesterol goals (199). As can statins. Niacin is the most effective drug mented aspirin allergy, clopidogrel (75 be seen in Table 10, placebo-controlled for raising HDL cholesterol. It can signif- mg/day) should be used. (B) trials generally achieved LDL cholesterol icantly increase blood glucose at high ● Combination therapy with ASA (75– reductions of 30 – 40% from baseline. doses, but recent studies demonstrate that 162 mg/day) and clopidogrel (75 mg/ Hence, LDL cholesterol lowering of this at modest doses (750 –2,000 mg/day), day) is reasonable for up to a year after magnitude is an acceptable outcome for significant improvements in LDL choles- an acute coronary syndrome. (B) patients who cannot reach LDL choles- terol, HDL cholesterol, and triglyceride ● Aspirin therapy is not recommended in terol goals due to severe baseline eleva- levels are accompanied by only modest people under 30 years of age due to lack tions in LDL cholesterol and/or changes in glucose that are generally ame- of evidence of benefit and is contrain- intolerance of maximal, or any, statin nable to adjustment of diabetes therapy dicated in patients under the age of 21 doses. Additionally, for those with base- (205,206). years because of the associated risk of line LDL cholesterol minimally above 100 Combination therapy, with a statin Reye’s syndrome. (E) mg/dl, prescribing statin therapy to lower and a fibrate or a statin and niacin, may be LDL cholesterol about 30 – 40% from efficacious for treatment for all three lipid The use of aspirin in diabetes is reviewed baseline is probably more effective than fractions, but this combination is associ- in detail in the ADA technical review prescribing just enough to get LDL cho- ated with an increased risk for abnormal (157) and position statement (210) on lesterol slightly below 100 mg/dl. transaminase levels, myositis, or rhabdo- this topic. Aspirin has been recom- DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S31
  • 20. Standards of Medical Care mended for primary (211,212) and and other forms of treatment as a rou- microalbuminuria, cardiac autonomic secondary (213,214) prevention of car- tine component of diabetes care. (B) neuropathy, or smoking), aspirin and diovascular events in high-risk diabetic statin therapy (if not contraindicated) and nondiabetic individuals. One large Issues of smoking in diabetes are reviewed should be used to reduce the risk of meta-analysis and several clinical trials in detail in the ADA technical review (158) cardiovascular events. (B) demonstrate the efficacy of using aspirin and position statement (218) on this topic. ● In patients with CHF, TZD use is con- as a preventive measure for cardiovascu- A large body of evidence from epidemiolog- traindicated. (C) lar events, including stroke and myocar- ical, case-control, and cohort studies pro- ● Metformin may be used in patients with dial infarction. Many trials have shown an vides convincing documentation of the stable CHF if renal function is normal. 30% decrease in myocardial infarction causal link between cigarette smoking and It should be avoided in unstable or hos- and a 20% decrease in stroke in a wide health risks. Cigarette smoking contributes pitalized patients with CHF. (C) range of patients, including young and to one of every five deaths in the U.S. and is middle-aged patients, patients with and the most important modifiable cause of pre- Screening for CAD is reviewed in a re- without a history of CVD, men and mature death. Much of the prior work doc- cently updated consensus statement women, and patients with hypertension. umenting the impact of smoking on health (123). To identify the presence of CAD in Dosages used in most clinical trials did not separately discuss results on subsets diabetic patients without clear or sugges- ranged from 75 to 325 mg/day. There is of individuals with diabetes, suggesting that tive symptoms, a risk factor– based ap- little evidence to support any specific dose, the identified risks are at least equivalent to proach to the initial diagnostic evaluation but using the lowest possible dosage may those found in the general population. and subsequent follow-up has intuitive help reduce side effects (215). Conversely, a Other studies of individuals with diabetes appeal. However, recent studies con- randomized trial of 100 mg of aspirin daily consistently found a heightened risk of cluded that using this approach fails to showed less of a primary prevention effect, CVD and premature death among smokers. identify which patients will have silent without statistical significance, in the large Smoking is also related to the premature de- ischemia on screening tests (130,221). diabetic subgroup in contrast to significant velopment of microvascular complications Candidates for cardiac testing include benefit in those without diabetes (216), of diabetes and may have a role in the de- those with 1) typical or atypical cardiac raising the issue of aspirin resistance in velopment of type 2 diabetes. symptoms and 2) an abnormal resting elec- those with diabetes. A number of large randomized clini- trocardiogram (ECG). The screening of The systematic review of evidence for cal trials have demonstrated the efficacy asymptomatic patients remains controver- the U.S. Preventive Services Task Force and cost-effectiveness of smoking cessa- sial, especially as intensive medical therapy (USPSTF) estimated that aspirin reduced tion counseling in changing smoking be- indicated in diabetic patients at high risk for the risk for nonfatal and fatal MI (odds havior and reducing tobacco use. The CVD has an increasing evidence base for ratio 0.72 [95% CI 0.60 – 0.87]). The re- routine and thorough assessment of to- providing equal outcomes to invasive revas- view acknowledged the low numbers of bacco use is important as a means of pre- cularization, including in diabetic patients diabetic subjects in most trials but con- venting smoking or encouraging (222). There is also recent preliminary evi- cluded that subset analyses and a single cessation. Special considerations should dence that silent myocardial ischemia may trial in diabetic patients suggested that the include assessment of level of nicotine de- reverse over time, adding to the controversy estimates extended to those with diabetes pendence, which is associated with diffi- concerning aggressive screening strategies (211). The USPSTF stated that the risk- culty in quitting and relapse (219,220). (223). Finally, a recent randomized obser- to-benefit ratio favors aspirin use when Free telephone quit lines are available in vational trial presented at the ADA’s Scien- 5-year CHD risk equals or exceeds 3% each state (see www.naquitline.org). tific Sessions in June 2008 demonstrated no and suggested aspirin therapy be consid- clinical benefit to routine screening of ered for men 40 years of age, postmeno- 5. CHD screening and treatment asymptomatic patients with type 2 diabetes pausal women, and younger persons with and normal ECGs. Despite abnormal myo- CHD risk factors (including diabetes) cardial perfusion imaging in more than one (212). Recommendations in five patients, cardiac outcomes were es- There is no evidence for a specific age Screening sentially equal (and very low) in screened ● In asymptomatic patients, evaluate risk at which to start aspirin, but aspirin has versus unscreened patients. not been studied at ages 30 years. factors to stratify patients by 10-year risk, In all patients with diabetes, cardio- Clopidogrel has been demonstrated and treat risk factors accordingly. (B) vascular risk factors should be assessed at to reduce CVD events in diabetic individ- least annually. These risk factors include uals (217). Adjunctive therapy in the first Treatment dyslipidemia, hypertension, smoking, a year after acute coronary syndrome in ● In patients with known CVD, ACE in- positive family history of premature cor- very-high-risk patients, or as alternative hibitor (C), aspirin (A), and statin ther- onary disease, and the presence of micro- therapy in aspirin-intolerant patients, apy (A) (if not contraindicated) should or macroalbuminuria. Abnormal risk fac- should be considered. be used to reduce the risk of cardiovas- tors should be treated as described else- cular events. where in these guidelines. Patients at ● In patients with a prior myocardial in- increased CHD risk should receive aspirin 4. Smoking cessation farction, add -blockers (if not contra- and a statin and ACE inhibitor or ARB indicated) to reduce mortality. (A) therapy if hypertensive, unless there are Recommendations ● In patients 40 years of age with an- contraindications to a particular drug ● Advise all patients not to smoke. (A) other cardiovascular risk factor (hyper- class. While clear benefit exists for ACE ● Include smoking cessation counseling tension, family history, dyslipidemia, inhibitor and ARB therapy in patients S32 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 21. Position Statement with nephropathy or hypertension, the ● Reduction of protein intake to 0.8 –1.0 and can slow the decline in GFR in benefits in patients with CVD in the ab- g kg body wt 1 day 1 in individuals patients with macroalbuminuria sence of these conditions is less clear, es- with diabetes and the earlier stages of (180,181,232). In type 2 diabetes with pecially when LDL cholesterol is CKD and to 0.8 g kg body wt 1 hypertension and normoalbuminuria, concomitantly controlled (224,225) day 1 in the later stages of CKD may ACE inhibition has been demonstrated to improve measures of renal function delay progression to microalbuminuria (urine albumin excretion rate, GFR) (233). B. Nephropathy screening and and is recommended. (B) In addition, ACE inhibitors have been treatment ● When ACE inhibitors, ARBs, or diuret- shown to reduce major CVD outcomes ics are used, monitor serum creatinine (i.e., myocardial infarction, stroke, death) Recommendations and potassium levels for the develop- in patients with diabetes (174), thus fur- ment of acute kidney disease and hy- ther supporting the use of these agents in General recommendations perkalemia. (E) patients with microalbuminuria, a CVD ● To reduce the risk or slow the progres- ● Continued monitoring of urine albu- risk factor. ARBs have also been shown to sion of nephropathy, optimize glucose min excretion to assess both response reduce the rate of progression from mi- control. (A) to therapy and progression of disease is cro- to macroalbuminuria as well as ESRD ● To reduce the risk or slow the progres- recommended. (E) in patients with type 2 diabetes (234 – sion of nephropathy, optimize blood ● Consider referral to a physician experi- 236). Some evidence suggests that ARBs pressure control. (A) enced in the care of kidney disease have a smaller magnitude of rise in potas- when there is uncertainty about the eti- sium compared with ACE inhibitors in Screening ology of kidney disease (active urine people with nephropathy (237,238). It is ● Perform an annual test to assess urine sediment, absence of retinopathy, rapid important to note that the benefits of both albumin excretion in type 1 diabetic pa- decline in GFR), difficult management ACE inhibitors and ARBs in those with tients with diabetes duration of 5 issues, or advanced kidney disease. (B) diabetic nephropathy are strongly associ- years and in all type 2 diabetic patients, ated with the reduction in albuminuria. starting at diagnosis. (E) Diabetic nephropathy occurs in 20 – 40% Combinations of drugs that block the ren- ● Measure serum creatinine at least annu- of patients with diabetes and is the single nin-angiotensin-aldosterone system (e.g., ally in all adults with diabetes regard- leading cause of end-stage renal disease an ACE inhibitor plus an ARB, a miner- less of the degree of urine albumin (ESRD). Persistent albuminuria in the alocorticoid antagonist, or a direct renin excretion. The serum creatinine should range of 30 –299 mg/24 h (microalbu- inhibitor) have been shown to provide ad- be used to estimate GFR and stage the minuria) has been shown to be the earliest ditional lowering of albuminuria (239 – level of chronic kidney disease (CKD), stage of diabetic nephropathy in type 1 242). However, the long-term effects of if present. (E) diabetes and a marker for development of such combinations on renal or cardiovas- nephropathy in type 2 diabetes. Mi- cular outcomes have not yet been evalu- croalbuminuria is also a well-established ated in clinical trials. Treatment marker of increased CVD risk (226,227). Other drugs, such as diuretics, cal- ● In the treatment of the nonpregnant pa- Patients with microalbuminuria who cium channel blockers, and -blockers, tient with micro- or macroalbuminuria, progress to macroalbuminuria (300 should be used as additional therapy to either ACE inhibitors or ARBs should mg/24 h) are likely to progress to ESRD further lower blood pressure in patients be used. (A) (228,229). However, a number of inter- already treated with ACE inhibitors or ● While there are no adequate head-to- ventions have been demonstrated to re- ARBs (179) or as alternate therapy in the head comparisons of ACE inhibitors duce the risk and slow the progression of rare individual unable to tolerate ACE in- and ARBs, there is clinical trial support renal disease. hibitors or ARBs. for each of the following statements: Intensive diabetes management with Studies in patients with varying stages ● In patients with type 1 diabetes, hy- the goal of achieving near normoglycemia of nephropathy have shown that protein pertension, and any degree of albu- has been shown in large prospective ran- restriction helps slow the progression of minuria, ACE inhibitors have been domized studies to delay the onset of mi- albuminuria, GFR decline, and occur- shown to delay the progression of ne- croalbuminuria and the progression of rence of ESRD (243–246). Protein restric- phropathy. (A) micro- to macroalbuminuria in patients tion should be considered particularly in ● In patients with type 2 diabetes, hy- with type 1 (230,231) and type 2 (49,50) patients whose nephropathy seems to be pertension, and microalbuminuria, diabetes. The UKPDS provided strong ev- progressing despite optimal glucose and both ACE inhibitors and ARBs have idence that control of blood pressure can blood pressure control and use of ACE been shown to delay the progression reduce the development of nephropathy inhibitor and/or ARBs (246). to macroalbuminuria. (A) (163). In addition, large prospective ran- ● In patients with type 2 diabetes, hy- domized studies in patients with type 1 Assessment of albuminuria status pertension, macroalbuminuria, and diabetes have demonstrated that achieve- and renal function renal insufficiency (serum creatinine ment of lower levels of systolic blood Screening for microalbuminuria can be 1.5 mg/dl), ARBs have been shown pressure ( 140 mmHg) resulting from performed by measurement of the albu- to delay the progression of nephrop- treatment using ACE inhibitors provides a min-to-creatinine ratio in a random spot athy. (A) selective benefit over other antihyperten- collection (preferred method); 24-h or ● If one class is not tolerated, the other sive drug classes in delaying the progres- timed collections are more burdensome should be substituted. (E) sion from micro- to macroalbuminuria and add little to prediction or accuracy DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S33
  • 22. Standards of Medical Care Table 12—Definitions of abnormalities in albumin excretion sure, blood glucose, and hyperlipid- emia, and the potential need for renal Category Spot collection ( g/mg creatinine) replacement therapy. Normal 30 Microalbuminuria 30–299 C. Retinopathy screening and Macro (clinical)-albuminuria 300 treatment Recommendations (247,248). Measurement of a spot urine ter diagnosis of microalbuminuria and General recommendations for albumin only, whether by immunoas- institution of ACE inhibitor or ARB ther- ● To reduce the risk or slow the progres- say or by using a dipstick test specific for apy and blood pressure control is unclear. sion of retinopathy, optimize glycemic microalbumin, without simultaneously Continued surveillance can assess both control. (A) measuring urine creatinine, is somewhat response to therapy and progression of ● To reduce the risk or slow the progres- less expensive but susceptible to false- disease. Some suggest that reducing ab- sion of retinopathy, optimize blood negative and -positive determinations as a normal albuminuria ( 30 mg/g) to the pressure control. (A) result of variation in urine concentration normal or near-normal range may im- due to hydration and other factors. prove renal and cardiovascular prognosis, Screening Abnormalities of albumin excretion but this approach has not been formally ● Adults and children aged 10 years or are defined in Table 12. Because of vari- evaluated in prospective trials. older with type 1 diabetes should have ability in urinary albumin excretion, two Complications of kidney disease cor- an initial dilated and comprehensive of three specimens collected within a 3- to relate with level of kidney function. When eye examination by an ophthalmologist 6-month period should be abnormal be- the estimated GFR is 60 ml/min per or optometrist within 5 years after the fore considering a patient to have crossed 1.73 m2, screening for anemia, malnutri- onset of diabetes. (B) one of these diagnostic thresholds. Exer- tion, and metabolic bone disease is indi- ● Patients with type 2 diabetes should cise within 24 h, infection, fever, CHF, cated. Early vaccination against hepatitis have an initial dilated and comprehen- marked hyperglycemia, and marked hy- B is indicated in patients likely to progress sive eye examination by an ophthalmol- pertension may elevate urinary albumin to end-stage kidney disease. ogist or optometrist shortly after the excretion over baseline values. Consider referral to a physician ex- diagnosis of diabetes. (B) Information on presence of abnormal perienced in the care of kidney disease ● Subsequent examinations for type 1 urine albumin excretion in addition to when there is uncertainty about the eti- and type 2 diabetic patients should be level of GFR may be used to stage CKD. ology of kidney disease (active urine repeated annually by an ophthalmolo- The National Kidney Foundation classifi- sediment, absence of retinopathy, rapid gist or optometrist. Less frequent exams cation (Table 13) is primarily based on decline in GFR), difficult management (every 2–3 years) may be considered GFR levels and therefore differs from issues, or advanced kidney disease. The following one or more normal eye ex- other systems, in which staging is based threshold for referral may vary depend- ams. Examinations will be required primarily on urinary albumin excretion ing on the frequency with which a pro- more frequently if retinopathy is pro- (249). Studies have found decreased GFR vider encounters diabetic patients with gressing. (B) in the absence of increased urine albumin significant kidney disease. Consultation ● Women with preexisting diabetes who excretion in a substantial percentage of with a nephrologist when stage 4 CKD are planning pregnancy or who have adults with diabetes (250,251). Epidemi- develops has been found to reduce cost, become pregnant should have a com- ologic evidence suggests that a substantial improve quality of care, and keep peo- prehensive eye examination and be fraction of those with CKD in the setting ple off dialysis longer (253,254). How- counseled on the risk of development of diabetes have little or no detectable ever, nonrenal specialists should not and/or progression of diabetic retinop- albuminuria (250). Serum creatinine delay educating their patients about the athy. Eye examination should occur in should therefore be measured at least an- progressive nature of diabetic kidney the first trimester with close follow-up nually in all adults with diabetes, regard- disease, the renal preservation benefits throughout pregnancy and 1 year post- less of the degree of urine albumin of aggressive treatment of blood pres- partum. (B) excretion. Serum creatinine should be used to estimate GFR and to stage the level of Table 13—Stages of CKD CKD, if present. GFR can be estimated using formulae such as the Cockroft- GFR (ml/min per 1.73 m2 Gault equation or a prediction formula Stage Description body surface area) using data from the Modification of Diet and Renal Disease study (252). GFR 1 Kidney damage* with normal or increased GFR 90 calculators are available at http://www. 2 Kidney damage* with mildly decreased GFR 60–89 nkdep.nih.gov. Many clinical laboratories 3 Moderately decreased GFR 30–59 now report estimated GFR in addition to 4 Severely decreased GFR 15–29 serum creatinine. 5 Kidney failure 15 or dialysis The role of continued annual quanti- *Kidney damage defined as abnormalities on pathologic, urine, blood, or imaging tests. Adapted and tative assessment of albumin excretion af- reprinted with permission (248). S34 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 23. Position Statement Treatment among patients whose baseline evalua- experts. In-person exams are still neces- ● Promptly refer patients with any level of tion revealed high-risk characteristics sary when the photos are unacceptable macular edema, severe NPDR, or any (chiefly disc neovascularization or vitre- and for follow-up of abnormalities de- PDR to an ophthalmologist who is ous hemorrhage). Given the risks of mod- tected. This technology has great poten- knowledgeable and experienced in the est loss of visual acuity and contraction of tial in areas where qualified eye care management and treatment of diabetic the visual field from panretinal laser sur- professionals are not available and may retinopathy. (A) gery, such therapy is primarily recom- enhance efficiency and reduce costs when ● Laser photocoagulation therapy is indi- mended for eyes with PDR approaching the expertise of ophthalmologists can be cated to reduce the risk of vision loss in or having high-risk characteristics. utilized for more complex examinations patients with high-risk PDR and clini- The ETDRS (261) established the and for therapy (267). cally significant macular edema and in benefit of focal laser photocoagulation Results of eye examinations should be some cases of severe NPDR. (A) surgery in eyes with macular edema, par- documented and transmitted to the refer- ● The presence of retinopathy is not a ticularly those with clinically significant ring health care professional. For a de- contraindication to aspirin therapy for macular edema, with reduction of dou- tailed review of the evidence and further cardioprotection, as this therapy does bling of the visual angle (e.g., 20/50 to discussion of diabetic retinopathy, see the not increase the risk of retinal hemor- 20/100) from 20% in untreated eyes to ADA’s technical review and position state- rhage. (A) 8% in treated eyes. The ETDRS also veri- ment on this subject (268,269). fied the benefits of panretinal photocoag- Diabetic retinopathy is a highly specific ulation for high-risk PDR, but not for D. Neuropathy screening and vascular complication of both type 1 and mild or moderate NPDR. In older-onset treatment (270) type 2 diabetes, with prevalence strongly patients with severe NPDR or less-than- related to the duration of diabetes. Dia- high-risk PDR, the risk of severe vision Recommendations betic retinopathy is the most frequent loss or vitrectomy was reduced 50% by ● All patients should be screened for dis- cause of new cases of blindness among early laser photocoagulation surgery at tal symmetric polyneuropathy (DPN) at adults aged 20 –74 years. Glaucoma, cat- these stages. diagnosis and at least annually thereaf- aracts, and other disorders of the eye oc- Laser photocoagulation surgery in ter using simple clinical tests. (B) cur earlier and more frequently in people both trials was beneficial in reducing the ● Electrophysiological testing is rarely with diabetes. risk of further vision loss, but generally needed, except in situations where the In addition to duration of diabetes, not beneficial in reversing already dimin- clinical features are atypical. (E) other factors that increase the risk of, or ished acuity. This preventive effect and ● Screening for signs and symptoms of are associated with, retinopathy include the fact that patients with PDR or macular cardiovascular autonomic neuropathy chronic hyperglycemia (255), the pres- edema may be asymptomatic provide should be instituted at diagnosis of type ence of nephropathy (256), and hyper- strong support for a screening program to 2 diabetes and 5 years after the diagno- tension (257). Intensive diabetes detect diabetic retinopathy. sis of type 1 diabetes. Special testing is management with the goal of achieving As retinopathy is estimated to take at rarely needed and may not affect man- near normoglycemia has been shown in least 5 years to develop after the onset of agement or outcomes. (E) large prospective randomized studies to hyperglycemia (262), patients with type 1 ● Medications for the relief of specific prevent and/or delay the onset and pro- diabetes should have an initial dilated and symptoms related to DPN and auto- gression of diabetic retinopathy comprehensive eye examination within 5 nomic neuropathy are recommended, (45,49,50). Lowering blood pressure has years after the onset of diabetes. Patients as they improve the quality of life of the been shown to decrease the progression with type 2 diabetes, who generally have patient. (E) of retinopathy (163). Several case series had years of undiagnosed diabetes (263) and a controlled prospective study sug- and who have a significant risk of preva- The diabetic neuropathies are heteroge- gest that pregnancy in type 1 diabetic pa- lent diabetic retinopathy at time of diabe- neous with diverse clinical manifesta- tients may aggravate retinopathy tes diagnosis, should have an initial tions. They may be focal or diffuse. Most (258,259); laser photocoagulation sur- dilated and comprehensive eye examina- common among the neuropathies are gery can minimize this risk (259). tion soon after diagnosis. Examinations chronic sensorimotor DPN and auto- One of the main motivations for should be performed by an ophthalmolo- nomic neuropathy. Although DPN is a screening for diabetic retinopathy is the gist or optometrist who is knowledgeable diagnosis of exclusion, complex investi- established efficacy of laser photocoagu- and experienced in diagnosing the pres- gations to exclude other conditions are lation surgery in preventing vision loss. ence of diabetic retinopathy and is aware rarely needed. Two large trials, the Diabetic Retinopathy of its management. Subsequent examina- The early recognition and appropri- Study (DRS) and the Early Treatment Di- tions for type 1 and type 2 diabetic pa- ate management of neuropathy in the pa- abetic Retinopathy Study (ETDRS), pro- tients are generally repeated annually. tient with diabetes is important for a vide the strongest support for the Less frequent exams (every 2–3 years) number of reasons: 1) nondiabetic neu- therapeutic benefits of photocoagulation may be cost effective after one or more ropathies may be present in patients with surgery. normal eye exams (264 –266), while ex- diabetes and may be treatable; 2) a num- The DRS (260) showed that panreti- aminations will be required more fre- ber of treatment options exist for symp- nal photocoagulation surgery reduced the quently if retinopathy is progressing. tomatic diabetic neuropathy; 3) up to risk of severe vision loss from PDR from Examinations can also be done with 50% of DPN may be asymptomatic, and 15.9% in untreated eyes to 6.4% in retinal photographs (with or without di- patients are at risk of insensate injury to treated eyes. The benefit was greatest lation of the pupil) read by experienced their feet; 4) autonomic neuropathy may DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S35
  • 24. Standards of Medical Care Table 14—Table of drugs to treat symptomatic DPN optimization of control, but also with the avoidance of extreme blood glucose fluc- Class Examples Typical doses* tuations. Patients with painful DPN may benefit from pharmacological treatment Tricyclic drugs Amitriptyline 10–75 mg at bedtime of their symptoms: many agents have ef- Nortriptyline 25–75 mg at bedtime ficacy confirmed in published random- Imipramine 25–75 mg at bedtime ized controlled trials, with several FDA- Anticonvulsants Gabapentin 300–1,200 mg t.i.d. approved for the management of painful Carbamazepine 200–400 mg t.i.d. DPN. See Table 14 for examples of agents Pregabalin† 100 mg t.i.d. to treat DPN pain. 5-hydroxytryptamine and Duloxetine† 60–120 mg daily norepinephrine uptake Treatment of autonomic neuropathy inhibitor Gastroparesis symptoms may improve Substance P inhibitor Capsaicin cream 0.025–0.075% applied t.i.d. or q.i.d. with dietary changes and prokinetic *Dose response may vary; initial doses should be low and titrated up. †Has FDA indication for treatment of agents such as metoclopramide or eryth- painful diabetic neuropathy. romycin. Treatments for erectile dysfunc- tion may include phosphodiesterase type 5 inhibitors, intracorporeal or intraure- involve every system in the body; and 5) indicated by resting tachycardia ( 100 thral prostaglandins, vacuum devices, or cardiovascular autonomic neuropathy bpm), orthostasis (a fall in systolic blood penile prostheses. Interventions for other causes substantial morbidity and mortal- pressure 20 mmHg upon standing manifestations of autonomic neuropathy ity. Specific treatment for the underlying without an appropriate heart rate re- are described in the ADA statement on nerve damage is currently not available, sponse), or other disturbances in auto- neuropathy (270). As with DPN treat- other than improved glycemic control, nomic nervous system function involving ments, these interventions do not change which may slow progression but not re- the skin, pupils, or gastrointestinal and the underlying pathology and natural his- verse neuronal loss. Effective symptom- genitourinary systems. tory of the disease process but may have a atic treatments are available for some Gastrointestinal neuropathies (e.g., positive impact on the quality of life of the manifestations of DPN and autonomic esophageal enteropathy, gastroparesis, patient. neuropathy. constipation, diarrhea, fecal inconti- nence) are common, and any section of Diagnosis of neuropathy the gastrointestinal tract may be affected. E. Foot care Gastroparesis should be suspected in in- Distal symmetric polyneuropathy dividuals with erratic glucose control or Recommendations Patients with diabetes should be screened ● For all patients with diabetes, perform with upper gastrointestinal symptoms annually for DPN using tests such as pin- without other identified cause. Evalua- an annual comprehensive foot exami- prick sensation, vibration perception tion of solid-phase gastric emptying using nation to identify risk factors predictive (using a 128-Hz tuning fork), 10-g mono- double-isotope scintigraphy may be done of ulcers and amputations. The foot ex- filament pressure sensation at the distal if symptoms are suggestive, but test re- amination should include inspection, plantar aspect of both great toes and sults often correlate poorly with symp- assessment of foot pulses, and testing metatarsal joints, and assessment of ankle toms. Constipation is the most common for loss of protective sensation (10-g reflexes. Combinations of more than one lower-gastrointestinal symptom but can monofilament plus testing any one of test have 87% sensitivity in detecting alternate with episodes of diarrhea. the following: vibration using 128-Hz DPN. Loss of 10-g monofilament percep- Diabetic autonomic neuropathy is tuning fork, pinprick sensation, ankle tion and reduced vibration perception also associated with genitourinary tract reflexes, or vibration perception predict foot ulcers (270). disturbances. In men, diabetic autonomic threshold). (B) Diabetic autonomic neuropathy (271) neuropathy may cause erectile dysfunc- ● Provide general foot self-care education The symptoms and signs of autonomic tion and/or retrograde ejaculation. Evalu- to all patients with diabetes. (B) dysfunction should be elicited carefully ation of bladder dysfunction should be ● A multidisciplinary approach is recom- during the history and physical examina- performed for individuals with diabetes mended for individuals with foot ulcers tion. Major clinical manifestations of dia- who have recurrent urinary tract infec- and high-risk feet, especially those with betic autonomic neuropathy include tions, pyelonephritis, incontinence, or a a history of prior ulcer or amputation. resting tachycardia, exercise intolerance, palpable bladder. (B) orthostatic hypotension, constipation, ● Refer patients who smoke, have loss of gastroparesis, erectile dysfunction, sudo- protective sensation and structural ab- motor dysfunction, impaired neurovas- Symptomatic treatments normalities, or have history of prior cular function, “brittle diabetes,” and DPN lower-extremity complications to foot hypoglycemic autonomic failure. The first step in management of patients care specialists for ongoing preventive Cardiovascular autonomic neuropa- with DPN should be to aim for stable and care and life-long surveillance. (C) thy, a CVD risk factor (93), is the most optimal glycemic control. Although con- ● Initial screening for peripheral arterial studied and clinically important form of trolled trial evidence is lacking, several disease (PAD) should include a history diabetic autonomic neuropathy. Cardio- observational studies suggest that neuro- for claudication and an assessment of vascular autonomic neuropathy may be pathic symptoms improve not only with the pedal pulses. Consider obtaining an S36 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 25. Position Statement ankle-brachial index (ABI), as many pa- ropathy. The clinical examination to iden- physical ability to conduct proper foot tients with PAD are asymptomatic. (C) tify LOPS is simple and requires no surveillance and care should be assessed. ● Refer patients with significant claudica- expensive equipment. Five simple clinical Patients with visual difficulties, physical tion or a positive ABI for further vascu- tests (use of a 10-g monofilament, vibra- constraints preventing movement, or cog- lar assessment and consider exercise, tion testing using a 128-Hz tuning fork, nitive problems that impair their ability to medications, and surgical options. (C) tests of pinprick sensation, ankle reflex assess the condition of the foot and to in- assessment, and testing vibration percep- stitute appropriate responses will need Amputation and foot ulceration, conse- tion threshold with a biothesiometer), other people, such as family members, to quences of diabetic neuropathy and/or each with evidence from well-conducted assist in their care. PAD, are common and major causes of prospective clinical cohort studies, are People with neuropathy or evidence morbidity and disability in people with considered useful in the diagnosis of of increased plantar pressure (e.g., ery- diabetes. Early recognition and manage- LOPS in the diabetic foot. The task force thema, warmth, callus, or measured ment of risk factors can prevent or delay agrees that any of the five tests listed could pressure) may be adequately managed adverse outcomes. be used by clinicians to identify LOPS, with well-fitted walking shoes or ath- The risk of ulcers or amputations is although ideally two of these should be letic shoes that cushion the feet and re- increased in people who have the follow- regularly performed during the screening distribute pressure. Callus can be ing risk factors: exam—normally the 10-g monofilament debrided with a scalpel by a foot care and one other test. One or more abnormal specialist or other health professional ● previous amputation tests would suggest LOPS, while at least with experience and training in foot ● past foot ulcer history two normal tests (and no abnormal test) care. People with bony deformities ● peripheral neuropathy would rule out LOPS. The last test listed, (e.g., hammertoes, prominent metatar- ● foot deformity vibration assessment using a biothesiom- sal heads, bunions) may need extra- ● peripheral vascular disease eter or similar instrument, is widely used wide or -depth shoes. People with ● vision impairment in the U.S.; however, identification of the extreme bony deformities (e.g., Charcot ● diabetic nephropathy (especially pa- patient with LOPS can easily be carried foot) who cannot be accommodated tients on dialysis) out without this or other expensive with commercial therapeutic footwear ● poor glycemic control equipment. may need custom-molded shoes. ● cigarette smoking Initial screening for PAD should in- Foot ulcers and wound care may re- clude a history for claudication and an quire care by a podiatrist, orthopedic or Many studies have been published pro- assessment of the pedal pulses. A diagnos- vascular surgeon, or rehabilitation spe- posing a range of tests that might usefully tic ABI should be performed in any pa- cialist experienced in the management identify patients at risk of foot ulceration, tient with symptoms of PAD. Due to the of individuals with diabetes. For a com- creating confusion among practitioners as high estimated prevalence of PAD in pa- plete discussion, see the ADA’s consen- to which screening tests should be tients with diabetes and the fact that many sus statement on diabetic foot wound adopted in clinical practice. An ADA task patients with PAD are asymptomatic, an care (274). force was therefore assembled in 2008 to ADA consensus statement on PAD (273) concisely summarize recent literature in suggested that a screening ABI be per- VII. DIABETES CARE IN this area and then recommend what formed in patients over 50 years of age SPECIFIC POPULATIONS should be included in the comprehensive and be considered in patients under 50 foot exam for adult patients with diabetes. years of age who have other PAD risk fac- A. Children and adolescents Their recommendations are summarized tors (e.g., smoking, hypertension, hyper- below, but clinicians should refer to the lipidemia, or duration of diabetes 10 1. Type 1 diabetes task force report (272) for further details years). Refer patients with significant Three-quarters of all cases of type 1 dia- and practical descriptions of how to per- symptoms or a positive ABI for further betes are diagnosed in individuals 18 form components of the comprehensive vascular assessment and consider exer- years of age. Because children are not sim- foot examination. cise, medications, and surgical options ply “small adults,” it is appropriate to con- At least annually, all adults with dia- (273). sider the unique aspects of care and betes should undergo a comprehensive Patients with diabetes and high-risk management of children and adolescents foot examination to identify high-risk foot conditions should be educated re- with type 1 diabetes. Children with dia- conditions. Clinicians should ask about garding their risk factors and appropriate betes differ from adults in many respects, history of previous foot ulceration or am- management. Patients at risk should un- including changes in insulin sensitivity putation, neuropathic or peripheral vas- derstand the implications of the loss of related to sexual maturity and physical cular symptoms, impaired vision, tobacco protective sensation, the importance of growth, ability to provide self-care, super- use, and foot care practices. A general in- foot monitoring on a daily basis, the vision in child care and school, and spection of skin integrity and musculo- proper care of the foot, including nail and unique neurologic vulnerability to hypo- skeletal deformities should be done in a skin care, and the selection of appropriate glycemia and DKA. Attention to such is- well-lit room. Vascular assessment should footwear. Patients with loss of protective sues as family dynamics, developmental include inspection and assessment of sensation should be educated on ways to stages, and physiologic differences related pedal pulses. substitute other sensory modalities (hand to sexual maturity are all essential in de- The neurologic exam recommended palpation, visual inspection) for surveil- veloping and implementing an optimal is designed to identify loss of protective lance of early foot problems. The patient’s diabetes regimen. Although recommen- sensation (LOPS) rather than early neu- understanding of these issues and their dations for children and adolescents are DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S37
  • 26. Standards of Medical Care Table 15—Plasma blood glucose and A1C goals for type 1 diabetes by age-group Plasma blood glucose goal range (mg/dl) Values by age (years) Before meals Bedtime/overnight A 1C Rationale Toddlers and preschoolers (0–6) 100–180 110–200 8.5% (but 7.5%) High risk and vulnerability to hypoglycemia School age (6–12) 90–180 100–180 8% Risks of hypoglycemia and relatively low risk of complications prior to puberty Adolescents and young adults (13–19) 90–130 90–150 7.5% ● Risk of severe hypoglycemia ● Developmental and psychological issues ● A lower goal ( 7.0%) is reasonable if it can be achieved without excessive hypoglycemia Key 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 A1C levels and to help assess glycemia in those on basal/bolus regimens. less likely to be based on clinical trial ev- While current standards for diabetes fits on long-term health outcomes of idence, because of current and historical management reflect the need to maintain achieving a lower A1C must be weighed restraints placed on conducting research glucose control as near to normal as safely against the unique risks of hypoglycemia in children, expert opinion and a review possible, special consideration must be and the difficulties achieving near normo- of available and relevant experimental given to the unique risks of hypoglycemia glycemia in children and youth. Age- data are summarized in the ADA state- in young children. Glycemic goals need to specific glycemic and A1C goals are ment on care of children and adolescents be modified to take into account the fact presented in Table 15. with type 1 diabetes (275). that most children 6 or 7 years of age Ideally, the care of a child or adoles- have a form of hypoglycemic unaware- b. Screening and management of cent with type 1 diabetes should be pro- ness. Their counterregulatory mecha- chronic complications in children and vided by a multidisciplinary team of nisms are immature and they may lack the adolescents with type 1 diabetes specialists trained in the care of children cognitive capacity to recognize and re- with pediatric diabetes. At the very least, spond to hypoglycemic symptoms, plac- i. Nephropathy education of the child and family should ing them at greater risk for severe be provided by health care providers hypoglycemia and its sequelae. In addi- Recommendations trained and experienced in childhood di- tion, and unlike the case in adults, young ● Annual screening for microalbumin- abetes and sensitive to the challenges children below the age of 5 years are at uria, with a random spot urine sample posed by diabetes in this age-group. At risk for permanent cognitive impairment for microalbumin-to-creatinine ratio, the time of initial diagnosis, it is essential after episodes of severe hypoglycemia should be initiated once the child is 10 that diabetes education be provided in a (276 –278). Extensive evidence indicates years of age and has had diabetes for 5 timely fashion, with the expectation that that near normalization of blood glucose years. (E) the balance between adult supervision levels is seldom attainable in children and ● Confirmed, persistently elevated mi- and self-care should be defined by, and adolescents after the honeymoon (remis- croalbumin levels on two additional will evolve according to, physical, psy- sion) period. The A1C level achieved in urine specimens should be treated with chological, and emotional maturity. MNT the “intensive” adolescent cohort of the an ACE inhibitor, titrated to normaliza- should be provided at diagnosis, and at DCCT group was 1% higher than that tion of microalbumin excretion if pos- least annually thereafter, by an individual achieved by adult DCCT subjects and sible. (E) experienced with the nutritional needs of above current ADA recommendations for the growing child and the behavioral is- patients in general. However, the in- ii. Hypertension sues that have an impact on adolescent creased frequency of use of basal bolus diets, including risk for disordered eating. regimens (including insulin pumps) in Recommendations youth from infancy through adolescence ● Treatment of high-normal blood pres- a. Glycemic control has been associated with more children sure (systolic or diastolic blood pres- reaching ADA blood glucose targets sure consistently between the 90 –95th Recommendations (279,280) in those families in which both percentile for age, sex, and height) ● Consider age when setting glycemic parents and the child with diabetes are should include dietary intervention goals in children and adolescents with motivated to perform the required diabe- and exercise aimed at weight control type 1 diabetes, with less stringent goals tes-related tasks. and increased physical activity, if ap- for younger children. (E) In selecting glycemic goals, the bene- propriate. If target blood pressure is not S38 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 27. Position Statement reached with 6 –12 months of lifestyle Treatment Although retinopathy most commonly intervention, pharmacologic treatment ● Initial therapy should consist of optimi- occurs after the onset of puberty and after should be initiated. (E) zation of glucose control and MNT us- 5–10 years of diabetes duration, it has ● Pharmacologic treatment of high blood ing a Step 2 AHA diet aimed at a been reported in prepubertal children pressure (systolic or diastolic blood decrease in the amount of saturated fat and with diabetes duration of only 1–2 pressure consistently above the 95th in the diet. (E) years. Referrals should be made to eye percentile for age, sex, and height or ● After the age of 10, the addition of a care professionals with expertise in dia- consistently 130/80 mmHg for ado- statin is recommended in patients who, betic retinopathy, an understanding of lescents) should be initiated along with after MNT and lifestyle changes, have the risk for retinopathy in the pediatric lifestyle intervention as soon as the di- LDL 160 mg/dl (4.1 mmol/l) or LDL population, and experience in counseling agnosis is confirmed. (E) cholesterol 130 mg/dl (3.4 mmol/l) the pediatric patient and family on the ● ACE inhibitors should be considered and one or more CVD risk factors. (E) importance of early prevention/ for the initial treatment of hyperten- ● The goal of therapy is an LDL choles- intervention. sion. (E) terol value 100 mg/dl (2.6 mmol/l). ● The goal of treatment is a blood pres- (E) v. Celiac disease sure consistently 130/80 or below the 90th percentile for age, sex, and height, People diagnosed with type 1 diabetes in Recommendations whichever is lower. (E) childhood have a high risk of early sub- ● Patients with type 1 diabetes should be clinical (281–283) and clinical (284) screened for celiac disease by measur- Hypertension in childhood is defined as CVD. Although intervention data are ing tissue transglutaminase or anti- an average systolic or diastolic blood pres- lacking, the AHA categorizes type 1 chil- endomysial antibodies, with sure 95th percentile for age, sex, and dren in the highest tier for cardiovascular documentation of normal serum IgA height percentile measured on at least 3 risk and recommends both lifestyle and levels, soon after the diagnosis of diabe- separate days. “High-normal” blood pres- pharmacologic treatment for those with tes. (E) elevated LDL cholesterol levels ● Testing should be repeated if growth sure is defined as an average systolic or diastolic blood pressure 90th but 95th (285,286). Initial therapy should be with failure, failure to gain weight, weight percentile for age, sex, and height percen- a Step 2 AHA diet, which restricts satu- loss, or gastroenterologic symptoms oc- tile measured on at least 3 separate days. rated fat to 7% of total calories and re- cur. (E) stricts dietary cholesterol to 200 mg per ● Consideration should be given to peri- Normal blood pressure levels for age, sex, and height and appropriate methods for day. Data from randomized clinical trials odic re-screening of asymptomatic in- determinations are available online at in children as young as 7 months of age dividuals. (E) indicate that this diet is safe and does not ● Children with positive antibodies www.nhlbi.nih.gov/health/prof/heart/ hbp/hbp_ped.pdf. interfere with normal growth and devel- should be referred to a gastroenterolo- opment (287,288). gist for evaluation. (E) For children over the age of 10 with ● Children with confirmed celiac disease iii. Dyslipidemia persistent elevation of LDL cholesterol should have consultation with a dietitian despite lifestyle therapy, statins should be and placed on a gluten-free diet. (E) Recommendations considered. Neither long-term safety nor cardiovascular outcome efficacy has been Celiac disease is an immune-mediated Screening established for children. However, recent disorder that occurs with increased fre- ● If there is a family history of hypercho- studies have shown short-term safety quency in patients with type 1 diabetes lesterolemia (total cholesterol 240 equivalent to that seen in adults and effi- (1–16% of individuals compared with mg/dl) or a cardiovascular event before cacy in lowering LDL cholesterol levels, 0.3–1% in the general population) age 55 years, or if family history is un- improving endothelial function, and (292,293). Symptoms of celiac disease in- known, then a fasting lipid profile causing regression of carotid intimal clude diarrhea, weight loss or poor weight should be performed on children 2 thickening (289 –291). No statin is ap- gain, growth failure, abdominal pain, years of age soon after diagnosis (after proved for use under the age of 10, and chronic fatigue, malnutrition due to mal- glucose control has been established). statin treatment should generally not be absorption, and other gastrointestinal If family history is not of concern, then used in type 1 children before this age. problems and unexplained hypoglycemia the first lipid screening should be per- or erratic blood glucose concentrations. formed at puberty ( 10 years). All chil- iv. Retinopathy dren diagnosed with diabetes at or after vi. Hypothyroidism puberty should have a fasting lipid pro- Recommendations file performed soon after diagnosis ● The first ophthalmologic examination Recommendations (after glucose control has been estab- should be obtained once the child is ● Patients with type 1 diabetes should be lished). (E) 10 years of age and has had diabetes screened for thyroid peroxidase and ● For both age-groups, if lipids are abnor- for 3–5 years. (E) thyroglobulin antibodies at diagnosis. mal, annual monitoring is recom- ● After the initial examination, annual (E) mended. If LDL cholesterol values are routine follow-up is generally recom- ● TSH concentrations should be mea- within the accepted risk levels ( 100 mended. Less frequent examinations sured after metabolic control has been mg/dl [2.6 mmol/l]), a lipid profile may be acceptable on the advice of an established. If normal, they should be should be repeated every 5 years. (E) eye care professional. (E) rechecked every 1–2 years, or if the pa- DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S39
  • 28. Standards of Medical Care tient develops symptoms of thyroid croalbuminuria at diagnosis (298), it is grams were multidisciplinary and de- dysfunction, thyromegaly, or an abnor- recommended that screening for the co- signed to train patients in diabetes self- mal growth rate. Free T4 should be morbidities and complications of diabe- management with diet, intensified insulin measured if TSH is abnormal. (E) tes, including fasting lipid profile, therapy, and SMBG. Goals were set to microalbuminuria assessment, and di- achieve normal blood glucose concentra- Autoimmune thyroid disease is the most lated eye examinations, begin at the time tions, and 80% of subjects achieved common autoimmune disorder associ- of diagnosis. The ADA consensus state- normal A1C concentrations before they ated with diabetes, occurring in 17–30% ment on this subject (22) provides guid- became pregnant (299 –303). In all five of patients with type 1 diabetes (294). The ance on the prevention, screening, and studies, the incidence of major congenital presence of thyroid autoantibodies is pre- treatment of type 2 diabetes and its co- malformations in women who partici- dictive of thyroid dysfunction, generally morbidities in young people. pated in preconception care (range 1.0 – hypothyroidism but less commonly hy- 1.7% of infants) was much lower than the perthyroidism (295). Subclinical hypo- B. Preconception care incidence in women who did not partici- thyroidism may be associated with pate (range 1.4 –10.9% of infants). One increased risk of symptomatic hypoglyce- Recommendations limitation of these studies is that partici- mia (296) and with reduced linear growth ● A1C levels should be as close to normal as pation in preconception care was self- (297). Hyperthyroidism alters glucose possible ( 7%) in an individual patient selected rather than randomized. Thus, it metabolism, potentially resulting in dete- before conception is attempted. (B) is impossible to be certain that the lower rioration of metabolic control. ● Starting at puberty, preconception malformation rates resulted fully from c. “Adherence.” No matter how sound counseling should be incorporated in improved diabetes care. Nonetheless, the the medical regimen, it can only be as the routine diabetes clinic visit for all evidence supports the concept that mal- good as the ability of the family and/or women of child-bearing potential. (C) formations can be reduced or prevented individual to implement it. Family in- ● Women with diabetes who are contem- by careful management of diabetes before volvement in diabetes remains an impor- plating pregnancy should be evaluated pregnancy. tant component of optimal diabetes and, if indicated, treated for diabetic Planned pregnancies greatly facilitate management throughout childhood and retinopathy, nephropathy, neuropathy, preconception diabetes care. Unfortu- into adolescence. Health care providers and CVD. (E) nately, nearly two-thirds of pregnancies who care for children and adolescents, ● Medications used by such women in women with diabetes are unplanned, therefore, must be capable of evaluating should be evaluated before conception, leading to a persistent excess of malfor- the behavioral, emotional, and psychoso- since drugs commonly used to treat di- mations in infants of diabetic mothers. To cial factors that interfere with implemen- abetes and its complications may be minimize the occurrence of these devas- tation and then must work with the contraindicated or not recommended tating malformations, standard care for all individual and family to resolve problems in pregnancy, including statins, ACE women with diabetes who have child- that occur and/or to modify goals as ap- inhibitors, ARBs, and most noninsulin bearing potential, beginning at the onset propriate. therapies. (E) of puberty or at diagnosis, should include d. School and day care. Since a sizable 1) education about the risk of malforma- portion of a child’s day is spent in school, Major congenital malformations remain tions associated with unplanned pregnan- close communication with school or day the leading cause of mortality and serious cies and poor metabolic control and 2) care personnel is essential for optimal di- morbidity in infants of mothers with type use of effective contraception at all times, abetes management, safety, and maximal 1 and type 2 diabetes. Observational stud- unless the patient has good metabolic academic opportunities. See Section ies indicate that the risk of malformations control and is actively trying to conceive. V.III.B, Diabetes Care in the School and increases continuously with increasing Women contemplating pregnancy Day Care Setting, for further discussion. maternal glycemia during the first 6 – 8 need to be seen frequently by a multidis- weeks of gestation, as defined by first- ciplinary team experienced in the man- 2. Type 2 diabetes trimester A1C concentrations. There is no agement of diabetes before and during The incidence of type 2 diabetes in ado- threshold for A1C values below which pregnancy. The goals of preconception lescents is increasing, especially in ethnic risk disappears entirely. However, mal- care are to 1) involve and empower the minority populations (20). Distinction formation rates above the 1–2% back- patient in the management of her diabe- between type 1 and type 2 diabetes in ground rate of nondiabetic pregnancies tes, 2) achieve the lowest A1C test results children can be difficult, since the preva- appear to be limited to pregnancies in possible without excessive hypoglycemia, lence of overweight in children continues which first-trimester A1C concentrations 3) assure effective contraception until sta- to rise and since autoantigens and ketosis are 1% above the normal range for a ble and acceptable glycemia is achieved, may be present in a substantial number of nondiabetic pregnant woman. and 4) identify, evaluate, and treat long- patients with features of type 2 diabetes Preconception care of diabetes ap- term diabetic complications such as reti- (including obesity and acanthosis nigri- pears to reduce the risk of congenital mal- nopathy, nephropathy, neuropathy, cans). Such a distinction at the time of formations. Five nonrandomized studies hypertension, and CHD. diagnosis is critical because treatment compared rates of major malformations in Among the drugs commonly used in regimens, educational approaches, and infants between women who participated the treatment of patients with diabetes, a dietary counsel will differ markedly be- in preconception diabetes care programs number may be relatively or absolutely tween the two diagnoses. Because type 2 and women who initiated intensive diabe- contraindicated during pregnancy. St- diabetes has a significant incidence of tes management after they were already atins are category X (contraindicated for hypertension, dyslipidemia, and mi- pregnant. The preconception care pro- use in pregnancy) and should be discon- S40 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 29. Position Statement tinued before conception, as should ACE riatric syndromes, such as polypharmacy, other cardiovascular risk factors rather than inhibitors (304). ARBs are category C depression, cognitive impairment, uri- from tight glycemic control alone. There is (risk cannot be ruled out) in the first tri- nary incontinence, injurious falls, and strong evidence from clinical trials of the mester but category D (positive evidence persistent pain. value of treating hypertension in the elderly of risk) in later pregnancy and should The American Geriatric Society’s (308,309). There is less evidence for lipid- generally be discontinued before preg- guidelines for improving the care of the lowering and aspirin therapy, although the nancy. Among the oral antidiabetic older person with diabetes (307) have in- benefits of these interventions for primary agents, metformin and acarbose are clas- fluenced the following discussion and and secondary prevention are likely to ap- sified as category B (no evidence of risk in recommendations. The care of older ply to older adults whose life expectancies humans) and all others as category C. Po- adults with diabetes is complicated by equal or exceed the time frames seen in clin- tential risks and benefits of oral antidia- their clinical and functional heterogene- ical trials. betic agents in the preconception period ity. Some older individuals developed di- Special care is required in prescribing must be carefully weighed, recognizing abetes years earlier and may have and monitoring pharmacologic therapy in that data are insufficient to establish the significant complications; others who are older adults. Metformin is often contrain- safety of these agents in pregnancy. newly diagnosed may have had years of dicated because of renal insufficiency or For further discussion of preconcep- undiagnosed diabetes with resultant com- significant heart failure. TZDs can cause tion care, see the ADA’s technical review plications or may have few complications fluid retention, which may exacerbate or (305) and position statement (306) on from the disease. Some older adults with lead to heart failure. They are contraindi- this subject. diabetes are frail and have other underly- cated in patients with CHF (New York ing chronic conditions, substantial diabe- Heart Association class III and IV) and if C. Older adults tes-related comorbidity, or limited used at all should be used very cautiously physical or cognitive functioning. Other in those with, or at risk for, milder degrees Recommendations older individuals with diabetes have little of CHF. Sulfonylureas, other insulin ● Older adults who are functional, cogni- comorbidity and are active. Life expectan- secretagogues, and insulin can cause hy- tively intact, and have significant life cies are highly variable for this popula- poglycemia. Insulin use requires that pa- expectancy should receive diabetes tion, but often longer than clinicians tients or caregivers have good visual and treatment using goals developed for realize. Providers caring for older adults motor skills and cognitive ability. Drugs younger adults. (E) with diabetes must take this heterogeneity should be started at the lowest dose and ● Glycemic goals for older adults not meet- into consideration when setting and pri- titrated up gradually until targets are ing the above criteria may be relaxed us- oritizing treatment goals. reached or side effects develop. ing individual criteria, but hyperglycemia There are few long-term studies in Screening for diabetes complications in leading to symptoms or risk of acute hy- older adults demonstrating the benefits of older adults also should be individualized. perglycemic complications should be intensive glycemic, blood pressure, and Particular attention should be paid to com- avoided in all patients. (E) lipid control. Patients who can be ex- plications that can develop over short peri- ● Other cardiovascular risk factors pected to live long enough to reap the ods of time and/or that would significantly should be treated in older adults with benefits of long-term intensive diabetes impair functional status, such as visual and consideration of the time frame of ben- management and who are active, have lower-extremity complications. efit and the individual patient. Treat- good cognitive function, and are willing ment of hypertension is indicated in to undertake the responsibility of self- virtually all older adults, and lipid and management should be encouraged to do VIII. DIABETES CARE IN aspirin therapy may benefit those with so and be treated using the goals for SPECIFIC SETTINGS life expectancy at least equal to the time younger adults with diabetes. frame of primary or secondary preven- For patients with advanced diabetes A. Diabetes care in the hospital tion trials. (E) complications, life-limiting comorbid ill- ● Screening for diabetes complications ness, or substantial cognitive or func- Recommendations should be individualized in older tional impairment, it is reasonable to set ● All patients with diabetes admitted to the adults, but particular attention should less intensive glycemic target goals. These hospital should have their diabetes be paid to complications that would patients are less likely to benefit from re- clearly identified in the medical record. lead to functional impairment. (E) ducing the risk of microvascular compli- (E) cations and more likely to suffer serious ● All patients with diabetes should have Diabetes is an important health condition adverse effects from hypoglycemia. How- an order for blood glucose monitoring, for the aging population; at least 20% of ever, patients with poorly controlled dia- with results available to all members of patients over the age of 65 years have di- betes may be subject to acute the health care team. (E) abetes, and this number can be expected complications of diabetes, including de- ● Goals for blood glucose levels: to grow rapidly in the coming decades. hydration, poor wound healing, and hy- ● Critically ill surgical patients’ blood Older individuals with diabetes have perglycemic hyperosmolar coma. glucose levels should be kept as close higher rates of premature death, func- Glycemic goals at a minimum should to 110 mg/dl (6.1 mmol/l) as possible tional disability, and coexisting illnesses avoid these consequences. and generally 140 mg/dl (7.8 such as hypertension, CHD, and stroke Although control of hyperglycemia mmol/l). (A) These patients require than those without diabetes. Older adults may be important in older individuals with an intravenous insulin protocol that with diabetes are also at greater risk than diabetes, greater reductions in morbidity has demonstrated efficacy and safety other older adults for several common ge- and mortality may result from control of in achieving the desired glucose DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S41
  • 30. Standards of Medical Care range without increasing risk for se- ● All patients with diabetes admitted to secondary in importance to the condition vere hypoglycemia. (E) the hospital should have an A1C ob- that prompted admission (313). ● Critically ill nonsurgical patients’ gly- tained if the result of testing in the pre- A rapidly growing body of literature cemic targets are less well defined. In- vious 2–3 months is not available. (E) supports targeted glucose control in the travenous insulin infusion protocols ● A diabetes education plan including hospital setting for potential improved targeting blood glucose levels “survival skills education” and fol- mortality, morbidity, and health eco- 110 –140 mg/dl have been shown low-up should be developed for each nomic outcomes. Hyperglycemia in the to reduced morbidity and mortality patient. (E) hospital may result from stress, decom- in some, but not all studies. Intrave- ● Patients with hyperglycemia in the hos- pensation of type 1 or type 2 or other nous insulin infusion protocols that pital who do not have a diagnosis of forms of diabetes, and/or may be iatro- effectively and safely keep blood glu- diabetes should have appropriate plans genic due to withholding of antihypergly- cose 140 mg/dl are recommended. for follow-up testing and care docu- cemic medications or administration of (C) mented at discharge. (E) hyperglycemia-provoking agents such as ● For non– critically ill patients, there glucocorticoids or vasopressors. is no clear evidence for specific blood The management of diabetes in the hos- glucose goals. Since cohort data sug- pital is extensively reviewed in an ADA 1. In-hospital hyperglycemia and gest that outcomes are better in hos- technical review (310). This review, as outcomes pitalized patients with fasting glucose well as a consensus statement by the a. General medicine and surgery. Ob- 126 mg/dl and all random glucoses American Association of Clinical Endocri- servational studies suggest an association 180 –200, these goals are reason- nologists (AACE) with co-sponsorship by between hyperglycemia and increased able if they can be safely achieved. ADA (311,312) and a report of a joint mortality. Surgical patients with at least Insulin is the preferred drug to treat ADA-AACE task force on the topic (313), one blood glucose value 220 mg/dl hyperglycemia in most cases. (E) form the basis for the discussion and (12.2 mmol/l) on the first postoperative ● Due to concerns regarding the risk of guidelines in this section. day have significantly higher infection hypoglycemia, some institutions may The literature on hospitalized pa- rates (315). consider these blood glucose levels to tients with hyperglycemia typically de- When admissions on general medi- be overly aggressive for initial targets. scribes three categories: cine and surgery units were studied, pa- Through quality improvement, glyce- tients with new hyperglycemia had mic goals should systematically be re- ● Medical history of diabetes: diabetes significantly increased in-hospital mortal- duced to the recommended levels. (E) previously diagnosed and acknowl- ity, as did patients with known diabetes. ● Scheduled prandial insulin doses edged by the patient’s treating physi- In addition, length of stay was higher for should be appropriately timed in rela- cian. the new hyperglycemic group, and pa- tion to meals and should be adjusted ● Unrecognized diabetes: hyperglycemia tients in either hyperglycemic group were according to point-of-care glucose lev- (fasting blood glucose 126 mg/dl or more likely to require intensive care unit els. The traditional sliding-scale insulin random blood glucose 200 mg/dl) oc- (ICU) care and transitional or nursing regimens are ineffective as mono- curring during hospitalization and con- home care. Better outcomes were demon- therapy and are generally not recom- firmed as diabetes after hospitalization strated in patients with fasting and admis- mended. (C) by standard diagnostic criteria but un- sion blood glucose 126 mg/dl (7 ● Using correction dose or “supplemen- recognized as diabetes by the treating mmol/l) and all random blood glucose tal” insulin to correct premeal hyper- physician during hospitalization. levels 200 mg/dl (11.1 mmol/l) (316). glycemia in addition to scheduled ● Hospital-related hyperglycemia: hyper- b. CVD and critical care. A significant prandial and basal insulin is recom- glycemia (fasting blood glucose 126 relationship exists between blood glucose mended. (E) mg/dl or random blood glucose 200 levels and mortality in the setting of acute ● Glucose monitoring with orders for mg/dl) occurring during the hospital- myocardial infarction. A meta-analysis of correction insulin should be initiated in ization that reverts to normal after hos- 15 studies compared in-hospital mortal- any patient not known to be diabetic pital discharge. ity in both hyper- and normoglycemic pa- who receives therapy associated with tients with and without diabetes. In high risk for hyperglycemia, including The prevalence of diabetes in hospitalized subjects without known diabetes whose high-dose glucocorticoids therapy, ini- adult patients is not precisely known. In admission blood glucose averaged 109.8 tiation of enteral or parenteral nutri- the year 2000, 12.4% of hospital dis- mg/dl (6.1 mmol/l), the relative risk for tion, or other medications such as charges in the U.S. listed diabetes as a in-hospital mortality was increased signif- octreotide or immunosuppressive diagnosis, but this is likely an underesti- icantly. When diabetes was present and medications. (B) If hyperglycemia is mate. The prevalence of diabetes in hos- admission glucose averaged 180 mg/dl documented and persistent, initiation pitalized adults is conservatively (10 mmol/l), risk of death was moderately of basal/bolus insulin therapy may be estimated at 12–25%, depending on the increased compared with patients who necessary. Such patients should be thoroughness used in identifying pa- had diabetes but less hyperglycemia on treated to the same glycemic goals as tients. In the year 2003, there were 5.1 admission (317). Another study (318) patients with known diabetes. (E) million hospitalizations with diabetes as a demonstrated a strong independent rela- ● A plan for treating hypoglycemia listed diagnosis, a 2.3-fold increase over tionship between admission blood glu- should be established for each patient. 1980 rates (314). cose values and both in-hospital and Episodes of hypoglycemia in the hospi- The management of hyperglycemia in 1-year mortality; rates were significantly tal should be tracked. (E) the hospital was traditionally considered lower in subjects with admission plasma S42 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 31. Position Statement glucose 100.8 mg/dl (5.6 mmol/l) than glucose 80 –110 mg/dl [4.4 – 6.1 mmol/l]) 2. Glycemic targets in hospitalized in those with plasma glucose 199.8 mg/dl or conventional therapy. Intensive insulin patients (11 mmol/l). therapy achieved a mean blood glucose of There is relatively strong evidence from These studies focused on admission 103 mg/dl (5.7 mmol/l) and was associ- randomized controlled trials for a glyce- blood glucose as a predictor of outcomes, ated with reduced mortality during the mic target of blood glucose 110 mg/dl rather than inpatient glycemic manage- ICU stay and decreased overall in- (6.1 mmol/l) in surgical patients in critical ment per se. Higher admission plasma hospital mortality (328). Hospital and care units (328 –330). However, in sev- glucose levels in patients with a prior his- ICU survival were linearly associated with eral studies of critically ill medical pa- tory of diabetes could reflect the degree of ICU glucose levels, with the highest sur- tients (330,331,333), the incidence of glycemic control in the outpatient setting, vival rates occurring in patients achieving severe hypoglycemia (blood glucose 40 thus linking outpatient glycemic control an average blood glucose 110 mg/dl mg/dl) was approximately threefold to outcomes in the inpatient population. (6.1 mmol/l) (329). greater in intensively treated patients. The In patients without a prior history of dia- A subsequent study of a similar inter- identification of hypoglycemia as an inde- betes, admission hyperglycemia could vention in patients in a medical ICU (330) pendent risk factor for death in the med- represent case finding of patients with showed that the group receiving intensive ical ICU population (334) may merit previously undiagnosed diabetes, an un- insulin therapy had reduced morbidity caution in widely promoting the 80 –110 masking of risk in a population at high but no difference in mortality overall. mg/dl target range for all critically ill risk for diabetes or more severe illness at Death rates were significantly lower in populations. admission. those patients who were treated for longer For patients in general medical- In the initial Diabetes and Insulin- than 3 days; but these patients could not surgical units, the evidence for specific Glucose Infusion in Acute Myocardial In- be identified before therapy. In another glycemic goals is less definitive. Epidemi- farction (DIGAMI) study (319,320), study using a similar intervention target- ologic and physiologic data suggest that insulin-glucose infusion followed by at ing a blood glucose range of 4.4 – 6.1 higher blood glucose levels are associated least 3 months of subcutaneous insulin mmol in patients admitted with sepsis, no with worse outcomes, but whether glu- treatment in diabetic patients with acute difference in mortality from the conven- cose is simply a marker of the severity of myocardial infarction improved long- tionally treated group was observed. underlying illness or a mediator of ad- term survival. Mean blood glucose in the There were more episodes of hypoglyce- verse outcomes is unclear. Glycemic tar- intensive insulin intervention arm was gets similar to those of outpatients may be mia, defined as a blood glucose 40 172.8 mg/dl (9.6 mmol/l), compared with difficult to achieve in the hospital due to mg/dl (2.2 mmol/l), and more serious ad- 210.6 mg/dl (11.7 mmol/l) in the “con- the effects of stress hyperglycemia, altered verse events in the group receiving inten- ventional” group. The broad range of nutritional intake, and multiple interrup- sive insulin therapy (331). blood glucose levels within each arm lim- tions to medical care. Blood glucose levels While an earlier meta-analysis con- its the ability to define specific blood glu- shown to be associated with improved cluded that insulin therapy in critically ill cose target thresholds. outcomes in these patients (fasting glu- Three more recent studies (321–323) patients had a beneficial effect on short- cose 126 mg/dl and all blood glucose using an insulin-glucose infusion did not term mortality in different clinical settings readings 180 –200 mg/dl) would ap- show a reduction in mortality in the inter- (332), a more recent meta-analysis, in- pear reasonable, if they can be safely vention groups. However, in each of these volving 29 studies and over 8,000 pa- achieved. studies, blood glucose levels were posi- tients, failed to show any mortality benefit In both the critical care and noncriti- tively correlated with mortality. In the from intensive glucose control. Tight glu- cal care venue, glycemic goals must take Hyperglycemia: Intensive Insulin Infu- cose control did reduce the relative risk of into account the individual patient’s situ- sion In Infarction (HI-5) study, a decrease septicemia by 26% (333). While this lat- ation as well as hospital system support in both CHF and reinfarction was ob- ter meta-analysis investigated strategies for achieving these goals. A continuous served in the group receiving intensive in- with target blood glucose levels of 80 – quality improvement strategy may facili- sulin therapy for at least 24 h. 110 mg/dl (4.4 – 6.1 mmol/l), studies tate gradual improvement in mean glyce- c. Cardiac surgery. Attainment of tar- with less stringent glucose targets were mia hospital wide. geted glucose control in patients with di- also included. Stratification by glucose abetes undergoing cardiac surgery is target did not demonstrate any heteroge- 3. Treatment options in hospitalized associated with reduced mortality and neity. The authors of this analysis as well patients risk of deep sternal wound infections as an accompanying editorial both recom- a. Noninsulin glucose-lowering agents. (324,325). Although these studies used mend that glycemic targets in critically ill No large studies have investigated the po- historical controls and were not random- patients be revisited (328 –331). tential roles of various noninsulin glu- ized, they support the concept that peri- While results from ongoing clinical cose-lowering agents on outcomes of operative hyperglycemia is an trials are still pending, it is clear that un- hospitalized patients with diabetes. Use of independent predictor of infection in pa- controlled hyperglycemia is associated the various noninsulin classes in the inpa- tients with diabetes (326), with the lowest with adverse outcomes in critically ill pa- tient setting presents some specific issues. mortality in patients with blood glucose tients and that achieving levels of glucose The long action of sulfonylureas and 150 mg/dl (8.3 mmol/l) (327). control below 140 mg/dl are reasonable, their predisposition to hypoglycemia in d. Critical care. A mixed group of patients provided that protocols that minimize patients not consuming their normal nu- with and without diabetes admitted to a risk for hypoglycemia are utilized and trition serve as relative contraindications surgical ICU were randomized to receive that personnel are well educated in the to routine use of these agents in the hos- intensive insulin therapy (target blood direct application of these protocols. pital (335). While the meglitinides, repa- DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S43
  • 32. Standards of Medical Care glinide and neteglinide, theoretically tain glucose control in most hospitalized veloped for use in the hospital is contin- would produce less hypoglycemia than patients with diabetes outside of the crit- uous intravenous infusion, using regular sulfonylureas, lack of clinical trial data for ical care arena. The components of the crystalline insulin. There is no advantage these agents, and the fact that they are daily insulin dose requirement can be met to using rapid acting analogs, whose primarily prandial in effect, would pre- by a variety of insulins, depending on the structural modifications increase the rate clude their use. The major limitation to particular hospital situation. Subcutane- of absorption from subcutaneous depots, metformin use in the hospital is a number ous insulin therapy should cover both in an intravenous insulin infusion. The of specific contraindications to its use, re- basal and nutritional needs and is subdi- medical literature supports the use of in- lated to risk of lactic acidosis, many of vided into scheduled insulin and supple- travenous insulin infusion in preference which occur in the hospital. The most mental, or correction-dose, insulin. to the subcutaneous route of insulin ad- common risk factors for lactic acidosis in Correction-dose insulin therapy is an im- ministration for several clinical indica- metformin-treated patients are cardiac portant adjunct to scheduled insulin, tions among nonpregnant adults. These disease, including decompensated CHF, both as a dose-finding strategy and as a include DKA and nonketotic hyperosmo- hypoperfusion, renal insufficiency, old supplement when rapid changes in insu- lar state; general preoperative, intraoper- age, and chronic pulmonary disease lin requirements lead to hyperglycemia. If ative, and postoperative care; the (336). Lactic acidosis is a rare complica- correction doses are frequently required, postoperative period following heart sur- tion in the outpatient setting (337), de- the appropriate scheduled insulin doses gery; following organ transplantation; spite the relative frequency of risk factors should be increased to accommodate the with cardiogenic shock; exacerbated hy- (338). However, in the hospital the risks increased insulin needs. There are cur- perglycemia during high-dose glucocorti- of hypoxia, hypoperfusion, and renal in- rently no published studies comparing coid therapy; type 1 patients who are sufficiency are much higher, and it is pru- human regular insulin with rapid-acting NPO; or in critical care illness in general. dent to avoid the use of metformin in analogs for use as correction-dose insulin. It may be used as a dose-finding strategy most patients. The traditional “sliding-scale” insulin in anticipation of initiation or reinitiation TZDs are not suitable for initiation in regimens, usually consisting of regular in- of subcutaneous insulin therapy in type 1 the hospital because of their delayed onset sulin without any intermediate or long- or type 2 diabetes. of effect. In addition, they increase intra- acting insulins, have been shown to be Many institutions use insulin infusion vascular volume, a particular problem in ineffective when used as monotherapy in algorithms that can be implemented by those predisposed to CHF and potentially patients with an established insulin re- nursing staff. Although numerous algo- a problem for patients with hemody- quirement (339 –341). Problems with rithms have been published, there have namic changes related to admission diag- sliding-scale insulin regimens include the been no head-to-head comparisons be- noses (e.g., acute coronary ischemia) or fact that the sliding-scale regimen pre- tween insulin infusion strategies. Algo- interventions common in hospitalized pa- scribed on admission is likely to be used rithms should incorporate the concepts tients. Pramlintide and exenatide work throughout the hospital stay without that maintenance requirements differ be- mainly by reducing postprandial hyper- modification, even when control remains tween patients and change over the glycemia and would therefore not be ap- poor. Additionally, sliding-scale insulin course of treatment. Ideally, intravenous propriate for patients not eating (nil per therapy treats hyperglycemia after it has insulin algorithms should consider both os, NPO) or with reduced caloric con- already occurred, instead of preventing current and previous glucose levels, the sumption. Furthermore, initiation of the occurrence of hyperglycemia. This rate of change of plasma glucose, and the these drugs in the inpatient setting would “reactive” approach can lead to rapid current intravenous insulin infusion rate. be problematic due to alterations in nor- changes in blood glucose levels, which For all algorithms, frequent (Q 1–2 h) mal food intake and their propensity to may exacerbate both hyper- and hypogly- bedside glucose testing is required. induce nausea initially. There is limited cemia. iii. Transition from intravenous to subcuta- experience, and no published data, on the A recent study demonstrated the neous insulin therapy. For those who will DPP-IV inhibitors in the hospital setting, safety and efficacy of using basal-bolus in- require subcutaneous insulin, the very although there are no specific safety con- sulin therapy utilizing weight-based dos- short half-life of intravenous insulin ne- cerns. They are mainly effective on post- ing in insulin-naïve hospitalized patients cessitates administering the first dose of prandial glucose and therefore would with type 2 diabetes (342). Glycemic con- subcutaneous insulin before discontinua- have limited effect in patients who are not trol, defined as a mean blood glucose tion of the intravenous insulin infusion. If eating. 140 mg/dl, was achieved in 68% of pa- short or rapid-acting insulin is used, it In summary, each of the major classes tients receiving basal-bolus insulin versus should be injected 1–2 h before stopping of noninsulin glucose-lowering drugs has only 38% of those receiving sliding-scale the infusion. If intermediate- or long- significant limitations for inpatient use. insulin alone. There were no differences acting insulin is used alone, it should be Additionally, they provide little flexibility in hypoglycemia between the two groups. injected 2–3 h before. A combination of or opportunity for titration in a setting It is important to note that the patients in short/rapid- and intermediate/long- where acute changes often demand these this study were obese, and the doses used acting insulin is usually preferred. Basal characteristics. Therefore, insulin, when in this study (0.4 to 0.5 units kg day 1) insulin therapy can be initiated at any used properly, is preferred for the major- are higher than what may be required in time of the day and should not be with- ity of hyperglycemic patients in the hos- patients who are more sensitive to insulin, held to await a specific dosing time, such pital setting. such as those who are lean or who have as bedtime. A recent clinical trial demon- b. Insulin type 1 diabetes. strated that a regimen using 80% of the i. Subcutaneous insulin therapy. Subcuta- ii. Intravenous insulin infusion. The only intravenous insulin requirement over the neous insulin therapy may be used to at- method of insulin delivery specifically de- preceding 24 h, divided into basal and S44 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 33. Position Statement bolus insulin components, was effective rapid-acting insulin in relation to meals, gram should be part of discharge plan- at achieving blood glucose levels between reduction of rate of administration of in- ning for all patients. 80 and 150 mg/dl following discontinua- travenous dextrose, and unexpected tion of the intravenous insulin (343). interruption of enteral feedings or paren- 8. MNT in the hospital teral nutrition. Hospital diets continue to be ordered by 4. Self-management in the hospital Despite the preventable nature of calorie levels based on the “ADA diet.” Self-management of diabetes in the hos- many inpatient episodes of hypoglyce- However, since 1994 the ADA has not en- pital may be appropriate for competent mia, institutions are more likely to have dorsed any single meal plan or specified adult patients who have a stable level of nursing protocols for the treatment of hy- percentages of macronutrients, and the consciousness, have reasonably stable poglycemia than for its prevention. term “ADA diet” should no longer be daily insulin requirements, successfully Tracking such episodes and analyzing used. Current nutrition recommenda- conduct self-management of diabetes at their causes are important quality im- tions advise individualization based on home, have physical skills needed to suc- provement activities. treatment goals, physiologic parameters, cessfully self-administer insulin and per- and medication usage. Because of the form SMBG, have adequate oral intake, 6. Diabetes care providers in the complexity of nutrition issues in the hos- and are proficient in carbohydrate count- hospital pital, a registered dietitian, knowledge- ing, use of multiple daily insulin injec- Inpatient diabetes management may be able and skilled in MNT, should serve as tions or insulin pump therapy, and sick- effectively provided by primary care phy- an inpatient team member. The dietitian day management. The patient and sicians, endocrinologists, or hospitalists, is responsible for integrating information physician, in consultation with nursing but involvement of appropriately trained about the patient’s clinical condition, eat- staff, must agree that patient self- specialists or specialty teams may reduce ing, and lifestyle habits and for establish- management is appropriate under the length of stay, improve glycemic control, ing treatment goals in order to determine conditions of hospitalization. For patients and improve outcomes (346 –349). In the a realistic plan for nutrition therapy conducting self-management in the hos- care of diabetes, implementation of stan- (351,352). pital, it is imperative that basal, prandial, dardized order sets for scheduled and cor- and correction doses of insulin and results rection-dose insulin may reduce reliance 9. Bedside blood glucose monitoring of bedside glucose monitoring be re- on sliding-scale management. A team ap- Implementing intensive diabetes therapy corded as part of the patient’s hospital proach is needed to establish hospital in the hospital setting requires frequent medical record. While many institutions pathways. To achieve glycemic targets and accurate blood glucose data. This allow patients on insulin pumps to con- associated with improved hospital out- measure is analogous to an additional “vi- tinue these devices in the hospital, others comes, hospitals will need multidisci- tal sign” for hospitalized patients with di- express concern regarding use of a device plinary support for using insulin infusion abetes. Bedside glucose monitoring using unfamiliar to staff, particularly in patients therapy outside of critical care units or capillary blood has advantages over labo- who are not able to manage their own will need to develop protocols for subcu- ratory venous glucose testing because the pump therapy. If a patient is too ill to taneous insulin therapy that effectively results can be obtained rapidly at the self-manage either multiple daily injec- and safely achieve glycemic targets (350). “point of care,” where therapeutic deci- tions or CSII, then appropriate subcuta- sions are made. neous doses can be calculated on the basis 7. DSME in the hospital Bedside blood glucose testing is usu- of their basal and bolus insulin needs dur- Teaching diabetes self-management to ally performed with portable meters that ing hospitalization, with adjustments for patients in hospitals is a challenging task. are similar or identical to devices for changes in nutritional or metabolic status. Patients are ill, under increased stress re- home SMBG. Staff training and ongoing lated to their hospitalization and diagno- quality control activities are important 5. Preventing hypoglycemia sis, and in an environment not conducive components of ensuring accuracy of the Hypoglycemia, especially in insulin- to learning. Ideally, people with diabetes results. Ability to track the occurrence of treated patients, is the leading limiting should be taught at a time and place con- hypo- and hyperglycemia is necessary. factor in the glycemic management of ducive to learning, as outpatients in a rec- Results of bedside glucose tests should be type 1 and type 2 diabetes (146). In the ognized program of diabetes education. readily available to all members of the hospital, multiple additional risk factors For the hospitalized patient, diabetes care team. for hypoglycemia are present, even “survival skills” education is generally a For patients who are eating, com- among patients who are neither “brittle” feasible approach. Patients and/or family monly recommended testing frequencies nor tightly controlled. Patients with or members receive sufficient information are premeal and at bedtime. For patients without diabetes may experience hypo- and training to enable safe care at home. not eating, testing every 4 – 6 h is usually glycemia in the hospital in association Those newly diagnosed with diabetes or sufficient for determining correction in- with altered nutritional state, heart fail- who are new to insulin and/or blood glu- sulin doses. Patients on continuous intra- ure, renal or liver disease, malignancy, in- cose monitoring need to be instructed venous insulin typically require hourly fection, or sepsis (344,345). Additional before discharge. Those patients hospital- blood glucose testing until the blood glu- triggering events leading to iatrogenic hy- ized because of a crisis related to diabetes cose levels are stable, then every 2 h. poglycemia include sudden reduction of management or poor care at home need corticosteroid dose, altered ability of the education to prevent subsequent episodes 10. Discharge planning patient to self-report symptoms, reduc- of hospitalization. An assessment of the It is important to anticipate the postdis- tion of oral intake, emesis, new NPO sta- need for a home health referral or referral charge antihyperglycemic regimen in all tus, inappropriate timing of short- or to an outpatient diabetes education pro- patients with diabetes or newly discov- DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S45
  • 34. Standards of Medical Care ered hyperglycemia. The optimal pro- blood glucose levels with needed food ing blood glucose monitoring and insulin gram will need to consider the type and and medication. (E) administration should also be accommo- severity of diabetes, the effects of the pa- dated. tient’s illness on blood glucose levels, and There are 186,300 individuals 20 The ADA and partner organizations the capacities and desires of the patient. years of age with diabetes in the U.S., have developed tools for school personnel Smooth transition to outpatient care most of whom attend school and/or some to provide a safe and nondiscriminatory should be ensured, especially in those type of day care and need knowledgeable educational environment for all students new to insulin therapy or in whom the staff to provide a safe environment. De- with diabetes (354,355). diabetes regimen has been substantially spite legal protections, including cover- altered during the hospitalization. All pa- age of children with diabetes under C. Diabetes care at diabetes camps tients in whom the diagnosis of diabetes is Section 504 of the Rehabilitation Act of (356) new should have, at minimum, “survival 1973, the Individuals with Disabilities skills” training before discharge. More ex- Education Act, and the Americans with Recommendations panded diabetes education can be ar- Disabilities Act, children in the school ● Each camper should have a standard- ranged in the community. For those with and day care setting still face discrimina- ized medical form completed by his/her hyperglycemia who do not require treat- tion. The ADA position statement on Di- family and the physician managing the ment upon discharge, follow-up testing abetes Care in the School and Day Care diabetes. (E) through their primary care physician Setting (353) provides the legal and med- ● Camp medical staff should be led by should be arranged, since many of these ical justifications for the recommenda- with a physician with expertise in man- individuals are found to have diabetes tions provided herein. aging type 1 and type 2 diabetes and when tested after discharge. Appropriate diabetes care in the include nurses (including diabetes ed- school and day care setting is necessary ucators and diabetes clinical nurse spe- for the child’s immediate safety, long- cialists) and registered dietitians with B. Diabetes care in the school and term well-being, and optimal academic expertise in diabetes. (E) day care setting (353) performance. Parents and the health care ● All camp staff, including physicians, team should provide school systems and nurses, dietitians, and volunteers, Recommendations day care providers with the information should undergo background testing to ● An individualized Diabetes Medical necessary for children with diabetes to ensure appropriateness in working Management Plan (DMMP) should be participate fully and safely in the school/ with children. (E) developed by the parent/guardian and day care experience by developing an in- the student’s personal diabetes health dividualized DMMP. The concept of specialized residential and care team with input from the parent/ The school nurse should be the key day camps for children with diabetes has guardian. (E) coordinator and provider of care and become widespread throughout the U.S. ● All school staff members who have re- should coordinate the training of an ade- and many other parts of the world. The sponsibility for a student with diabetes quate number of school personnel and mission of diabetes camps is to provide a should receive training that provides a ensure that if the school nurse is not camping experience in a safe environ- basic understanding of diabetes and a present at least one adult is present who is ment. An equally important goal is to en- student’s needs. (E) trained to perform the necessary diabetes able children with diabetes to meet and ● While the school nurse is the coordina- procedures (e.g., blood glucose monitor- share their experiences with one another tor and primary provider of diabetes ing and insulin and glucagon administra- while they learn to be more personally care, a small number of school person- tion) and provide the appropriate responsible for their disease. For this to nel should be trained in routine and response to high and low blood glucose occur, a skilled medical and camping staff emergency diabetes procedures (in- levels in a timely manner while the stu- must be available to ensure optimal safety cluding monitoring of blood glucose dent is at school, on field trips, participat- and an integrated camping/educational levels and administration of insulin and ing in school-sponsored extracurricular experience. glucagon) and in the appropriate re- activities, and on transportation provided Each camper should have a standard- sponse to high and low blood glucose by the school or day care facility. These ized medical form completed by his/her levels and should perform these diabe- school personnel need not be health care family and the physician managing the di- tes care tasks when the school nurse is professionals. abetes that details the camper’s past med- not available to do so. These school per- The student with diabetes should have ical history, immunization record, and sonnel need not be health care profes- immediate access to diabetes supplies at all diabetes regimen. The home insulin dos- sionals. (E) times, with supervision as needed. The stu- age should be recorded for each camper, ● As specified in the DMMP and as devel- dent should be able to obtain a blood glu- including type(s) of insulin used, number opmentally appropriate, the student cose level and respond to the results as and timing of injections, and the correc- with diabetes should have immediate quickly and conveniently as possible in the tion factor and carbohydrate ratios used access to diabetes supplies at all times classroom or wherever the child is in con- for determining bolus dosages for basal- and should be permitted to self-manage junction with a school-related activity, min- bolus regimens. Campers using CSII his or her diabetes in the classroom or imizing the need for missing instruction in should also have their basal rates speci- anywhere the student may be in con- the classroom and avoiding the risk of wors- fied. Because camp is often associated junction with a school activity. Such ening hypoglycemia or hyperglycemia if the with more physical activity than experi- self-management should include blood child must go somewhere else for treat- enced at home, the insulin dose may have glucose monitoring and responding to ment. The student’s desire for privacy dur- to be decreased during camp. S46 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 35. Position Statement The diabetes camping experience is 1 diabetes who are at high risk for DKA treatment of hypo- and hyperglycemia. short term, with food and activity differ- with omission of insulin. (E) Correctional staff should be trained in the ent than the home environment. Thus, ● Medications and MNT should be con- recognition and treatment of these condi- goals of glycemic control at camp are to tinued without interruption upon entry tions, and appropriate staff should be avoid extremes in blood glucose levels into the correctional environment. (E) trained to administer glucagon. Institu- rather than attempting optimization of in- ● In the correctional setting, policies and tions should implement a policy requir- tensive glycemic control. procedures should enable CBG moni- ing staff to notify a physician of all CBG During camp, a daily record of the toring to occur at the frequency neces- results outside of a specified range, as de- camper’s progress should be made, in- sitated by the patient’s glycemic control termined by the treating physician. cluding all blood glucose levels and insu- and diabetes regimen and should re- Correctional institutions should have lin dosages. To ensure safety and optimal quire staff to notify a physician of all systems in place to ensure that insulin ad- diabetes management, multiple blood CBG results outside of a specified ministration and meals are coordinated to glucose determinations should be made range, as determined by the treating prevent hypo- and hyperglycemia, taking throughout each 24-h period: before physician. (E) into consideration the transport of resi- meals, at bedtime, after or during pro- ● For all inter-institutional transfers, a dents off site and the possibility of emer- longed and strenuous activity, and in the medical transfer summary should be gency schedule changes. The frequency of middle of the night when indicated for transferred with the patient, and diabe- CBG monitoring will vary by patients’ gly- prior hypoglycemia. If major alterations tes supplies and medication should ac- cemic control and diabetes regimens. Pol- of a camper’s regimen appear to be indi- company the patient. (E) icies and procedures should ensure that cated, it is important to discuss this with ● Correctional staff should begin dis- the health care staff has adequate knowl- the camper and the family in addition to charge planning with adequate lead edge and skills to direct the management the child’s local physician. The record of time to ensure continuity of care and and education of individuals with diabetes. what transpired during camp should be facilitate entry into community diabe- Patients in jails may be housed for a discussed with the family at the end of the tes care. (E) short period of time before being trans- camp session and a copy sent to the ferred or released, and patients in prison child’s physician. At any given time, over 2 million people may be transferred within the system sev- Each camp should secure a formal re- are incarcerated in prisons and jails in the eral times during their incarceration. lationship with a nearby medical facility U.S., and it is estimated that nearly Transferring a patient with diabetes from so that camp medical staff can refer to this 80,000 of these inmates have diabetes. In one correctional facility to another re- facility for prompt treatment of medical addition, many more people with diabe- quires a coordinated effort, as does plan- emergencies. ADA requires that the camp tes pass through the corrections system in ning for discharge. The ADA position medical director be a physician with ex- a given year. statement on Diabetes Management in pertise in managing type 1 and type 2 di- People with diabetes in correctional Correctional Institutions (357) should be abetes. Nursing staff should include facilities should receive care that meets consulted for more information on this diabetes educators and diabetes clinical national standards. Correctional institu- topic. nurse specialists. Registered dietitians tions have unique circumstances that with expertise in diabetes should have in- need to be considered so that all standards E. Emergency and disaster put into the design of the menu and the of care may be achieved. Correctional in- preparedness (358) education program. All camp staff, in- stitutions should have written policies cluding medical, nursing, nutrition, and and procedures for the management of Recommendations volunteer, should undergo background diabetes and for training of medical and ● People with diabetes should maintain a testing to ensure appropriateness in correctional staff in diabetes care disaster kit that includes items impor- working with children. practices. tant to their diabetes self-management Reception screening should empha- and continuing medical care. (E) D. Diabetes management in size patient safety. In particular, rapid ● The kit should be reviewed and replen- correctional institutions (357) identification of all insulin-treated indi- ished at least twice yearly. (E) viduals with diabetes is essential in order Recommendations to identify those at highest risk for hypo- The difficulties encountered by people ● Correctional staff should be trained in and hyperglycemia and DKA. All insulin- with diabetes and their health care pro- the recognition, treatment, and appro- treated patients should have a CBG deter- viders in the wake of Hurricane Katrina priate referral for hypo- and hypergly- mination within 1–2 h of arrival. Patients (359) highlight the need for people with cemia, including serious metabolic with a diagnosis of diabetes should have a diabetes to be prepared for emergencies, decompensation. (E) complete medical history and physical ex- whether natural or otherwise, affecting a ● Patients with a diagnosis of diabetes amination by a licensed health care pro- region or just their household. Such pre- should have a complete medical history vider with prescriptive authority in a paredness will lessen the impact an emer- and physical examination by a licensed timely manner. It is essential that medica- gency may have on their condition. It is health care provider with prescriptive tion and MNT be continued without inter- recommended that people with diabetes authority in a timely manner upon en- ruption upon entry into the correctional keep a waterproof and insulated disaster try. Insulin-treated patients should system, as a hiatus in either medication or kit ready with items critically important have a capillary blood glucose (CBG) appropriate nutrition may lead to either se- to their self-management. These may in- determination within 1–2 h of arrival. vere hyper- or hypoglycemia. clude glucose testing strips, lancets, and a Staff should identify patients with type Patients must have access to prompt glucose-testing meter; medications in- DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S47
  • 36. Standards of Medical Care cluding insulin in a cool bag; syringes; medications used to the tools used to ad- laries, prior authorization, and provisions glucose tabs or gels; antibiotic ointments/ minister them and to monitor blood glu- such as competitive bidding can manage creams for external use; glucagon emer- cose levels. For most types of provider practices as well as costs to the gency kits; and photocopies of relevant employment, there is no reason to believe potential benefit of payors and patients. medical information, particularly medi- that the individual’s diabetes will put em- However, any controls should ensure that cation lists and recent lab tests/ ployees or the public at risk. In certain all classes of anti-diabetic agents with procedures if available. If possible, safety-sensitive positions the safety con- unique mechanisms of action and all prescription numbers should be noted, cern is whether the employee will become classes of equipment and supplies de- since many chain pharmacies throughout suddenly disoriented or incapacitated. signed for use with such equipment are the country will refill medications based Episodes of severe hypoglycemia should available to facilitate achieving glycemic on the prescription number alone. In ad- be examined by a health care professional goals and to reduce the risk of complica- dition, it may be important to carry a list with expertise in diabetes to determine tions. Without appropriate safeguards, of contacts for national organizations, any impact on safe performance of the undue controls could constitute an ob- such as the American Red Cross and ADA. job. Hyperglycemia is not typically a bar- struction of effective care. This disaster kit should be reviewed and rier to employment unless long-term Medicare and many other third-party replenished at least twice yearly. complications are present that interfere payors cover DSME (Centers for Medicare with the performance of the job. and Medicaid Services [CMS] term is dia- IX. DIABETES AND Most accommodations that help an betes self-management training [DSMT]) EMPLOYMENT (360) individual with diabetes do his or her job that meets the national standards for may be provided easily and with little or DSME (107) and MNT. The qualified Recommendations no cost to the employer. Typical accom- beneficiary, with referral from the pro- ● When questions arise about the medi- modations include breaks to test blood vider managing his or her diabetes, can cal fitness of a person with diabetes for glucose, administer insulin, or access receive an initial benefit of 10 h of DSMT a particular job, a health care professional food and beverages. Some individuals and 3 h of MNT, with a potential total of with expertise in treating diabetes should may need leave or a flexible work sched- 13 h of initial. More information on Medi- perform an individualized assessment; ule or accommodations for diabetes- care policy, including follow-up benefits, input from the treating physician should related complications. is available at www.diabetes.org/for- always be included. (E) The ADA position statement on Dia- health-professionals-and-scientists/ ● Proper safety assessments for employ- betes and Employment should be con- recognition.jsp or on the CMS Web sites: ment should include review of blood sulted for more information on this topic. DSME, www.cms.hhs.gov/DiabetesSelf- glucose test results, history of severe Management; and diabetes MNT, www. hypoglycemia, presence of hypoglyce- X. THIRD-PARTY cms.hhs.gov/MedicalNutritionTherapy, mia unawareness, and presence of dia- REIMBURSEMENT FOR reimbursement. betes-related complications but should DIABETES CARE, SELF- not include urine glucose or A1C/eAG MANAGEMENT XI. STRATEGIES FOR tests or be based on a general assess- EDUCATION, AND IMPROVING DIABETES ment of level of control. (E) SUPPLIES (361) CARE The implementation of the standards of Any person with diabetes, whether insu- Recommendations care for diabetes has been suboptimal in lin treated or noninsulin treated, should ● Patients and practitioners should have most clinical settings. A recent report be eligible for any employment for which access to all classes of antidiabetic med- (362) indicated that only 37% of adults he/she is otherwise qualified. Questions ications, equipment, and supplies with- with diagnosed diabetes achieved an A1C are sometimes raised by employers about out undue controls. (E) of 7%, only 36% had a blood pressure the safety and effectiveness of individuals ● MNT and DSME should be covered by 130/80 mmHg, and just 48% had a total with diabetes in a given job. When such insurance and other payors. (E) cholesterol 200 mg/dl. Most distressing questions are legitimately raised, a person was that only 7.3% of people with diabe- with diabetes should be individually as- To achieve optimal glucose control, the tes achieved all three treatment goals. sessed by a health care professional with person with diabetes must be able to ac- While numerous interventions to im- expertise in diabetes to determine cess health care providers who have ex- prove adherence to the recommended whether or not that person can safely and pertise in the field of diabetes. Treatments standards have been implemented, the effectively perform the particular duties of and therapies that improve glycemic con- challenge of providing uniformly effective the job in question. trol and reduce the complications of dia- diabetes care has thus far defied a simple Employment decisions should never betes will also significantly reduce health solution. A major contributor to subopti- be based on generalizations or stereotypes care costs. Access to the integral compo- mal care is a delivery system that too often regarding the effects of diabetes. “Blanket nents of diabetes care, such as health care is fragmented, lacks clinical information bans” that restrict individuals with diabe- visits, diabetes supplies and medications, capabilities, often duplicates services, and tes from certain jobs or classes of employ- and self-management education, is essen- is poorly designed for the delivery of ment solely because of the diagnosis of tial. All medications and supplies, such as chronic care. The Institute of Medicine diabetes or the use of insulin are medi- syringes, strips, and meters, related to the has called for changes so that delivery sys- cally and legally inappropriate and ignore daily care of diabetes must also be reim- tems provide care that is evidence based, the many advancements in diabetes man- bursed by third-party payors. patient centered, and systems oriented agement that range from the types of It is recognized that the use of formu- and takes advantage of information tech- S48 DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009
  • 37. Position Statement nologies that foster continuous quality automated reminders to health care Alexandria, VA, American Diabetes As- improvement. Collaborative, multidisci- professionals and patients, reporting of sociation, 2008 plinary teams should be best suited to process and outcome data to providers, 2. American Diabetes Association: Medical provide such care for people with chronic and especially identification of patients Management of Type 2 Diabetes. 6th ed. Alexandria, VA, American Diabetes As- conditions like diabetes and to empower at risk because of failure to achieve tar- sociation, 2008 patients’ performance of appropriate self- get values or a lack of reported values. 3. American Diabetes Association: Intensive management. Alterations in reimburse- ● Quality improvement programs com- Diabetes Management. Alexandria, VA, ment that reward the provision of quality bining continuous quality improve- American Diabetes Association, 2003 care, as defined by the attainment of qual- ment or other cycles of analysis and 4. Expert Committee on the Diagnosis and ity measures developed by such programs intervention with provider perfor- Classification of Diabetes Mellitus: Re- as the ADA/National Committee for Qual- mance data. port of the Expert Committee on the Di- ity Assurance Diabetes Provider Recogni- ● Practice changes, such as clustering of agnosis and Classification of Diabetes tion Program will also be required to dedicated diabetes visits into specific Mellitus. Diabetes Care 20:1183–1197, achieve desired outcome goals. times within a primary care practice 1997 The NDEP recently launched a new schedule and/or visits with multiple 5. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Fol- online resource to help health care profes- health care professionals on a single day low-up report on the diagnosis of diabe- sionals better organize their diabetes care. and group visits. tes mellitus. Diabetes Care 26:3160 – The www.betterdiabetescare.nih.gov ● Tracking systems with either an elec- 3167, 2003 Web site should help users design and tronic medical record or patient regis- 6. Davidson MB, Schriger DL, Peters AL, implement more effective health care de- try have been helpful at increasing Lorber B: Relationship between fasting livery systems for those with diabetes. adherence to standards of care by pro- plasma glucose and glycosylated hemo- In recent years, numerous health care spectively identifying those requiring globin: potential for false-positive diag- organizations, ranging from large health assessments and/or treatment modifi- noses of type 2 diabetes using new care systems such as the U.S. Veterans Ad- cations. They likely could have greater diagnostic criteria. JAMA 281:1203– ministration to small private practices, efficacy if they suggested specific ther- 1210, 1999 7. Nathan DM, Davidson MB, DeFronzo have implemented strategies to improve apeutic interventions to be considered RA, Heine RJ, Henry RR, Pratley R, Zin- diabetes care. Successful programs have for a particular patient at a particular man B: Impaired fasting glucose and im- published results showing improvement point in time (371). paired glucose tolerance: implications in process measures such as measurement ● A variety of nonautomated systems, for care. Diabetes Care 30:753–759, of A1C, lipids, and blood pressure. Effects such as mailing reminders to patients, 2007 on important intermediate outcomes, chart stickers, and flow sheets, have 8. Engelgau MM, Narayan KM, Herman such as mean A1C for populations, have been useful to prompt both providers WH: Screening for type 2 diabetes. Dia- been more difficult to demonstrate (363– and patients. betes Care 23:1563–1580, 2000 365), although examples do exist (366 – ● Availability of case or (preferably) care 9. Gabir MM, Hanson RL, Dabelea D, Im- 370). Successful interventions have been management services, usually by a peratore G, Roumain J, Bennett PH, Knowler WC: The 1997 American Dia- focused at the level of health care profes- nurse (372). Nurses, pharmacists, and betes Association and 1999 World sionals, delivery systems, and patients. other nonphysician health care profes- Health Organization criteria for hyper- Features of successful programs reported sionals using detailed algorithms work- glycemia in the diagnosis and prediction in the literature include: ing under the supervision of physicians of diabetes. Diabetes Care 23:1108 – and/or nurse education calls have also 1112, 2000 ● Improving health care professional ed- been helpful. Similarly, dietitians using 10. Knowler WC, Barrett-Connor E, Fowler ucation regarding the standards of care MNT guidelines have been demon- SE, Hamman RF, Lachin JM, Walker EA, through formal and informal education strated to improve glycemic control. Nathan DM: Reduction in the incidence programs. ● Availability and involvement of expert of type 2 diabetes with lifestyle interven- ● Delivery of DSME, which has been consultants, such as endocrinologists tion or metformin. N Engl J Med 346: shown to increase adherence to stan- and diabetes educators. 393– 403, 2002 11. Tuomilehto J, Lindstrom J, Eriksson JG, dard of care. Valle TT, Hamalainen H, Ilanne-Parikka ● Adoption of practice guidelines, with Evidence suggests that these individual P, Keinanen-Kiukaanniemi S, Laakso M, participation of health care profession- initiatives work best when provided as Louheranta A, Rastas M, Salminen V, als in the process. Guidelines should be components of a multifactorial interven- Uusitupa M: Prevention of type 2 diabe- readily accessible at the point of service, tion. 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