8. • In the Gruppo Italiano per lo Studio della
Sopravvivenza nell'Infarto Miocardico-2 (GISSI-2)
study of thrombolytic therapy in patients with
myocardial infarction, diabetes increased the rate of
death in men by 40 percent and women by 90
percent.
• In the Should We Emergently Revascularize
Occluded Coronaries for Cardiogenic Shock
(SHOCK) trial,[which evaluated a strategy of early
revascularization in patients with myocardial
infarction complicated by cardiogenic shock, 31.1
percent of the patients had diabetes, a much higher
percentage than in the population in general.
14. Diabetes Control and Complications Trial
(DCCT)
Compared effects of two diabetes
treatment regimens – standard
therapy and intensive control – on the
complications of diabetes
DCCT. New England Journal of Medicine, 329(14), September 30, 1993.
15. DCCT Findings
Glucose control is key to preventing
or delaying complications of diabetes
Any sustained lowering of blood
glucose helps, even if the person has
a history of poor control
DCCT. New England Journal of Medicine, 329(14), September 30, 1993.
16. DCCT Findings
Lowering blood glucose reduced risk of:
• Eye disease by 76%
• Kidney disease by 50%
• Nerve disease by 60%
DCCT. New England Journal of Medicine, 329(14), September 30, 1993.
17. Epidemiology of Diabetes Interventions and
Complications Study (EDIC)
• Observational study
• DCCT participants
• Looked at risk factors for long-term
complications
DCCT/EDIC N Engl J Med 2005: 353:2643-2653.
18. DCCT/EDIC
Metabolic Results
DCCT Intervention Training EDIC Observation
Conventional
EDIC mean 8.2%
Intensive
EDIC mean 8.0%
1 2 3 4 5 6 7 8 9
DCCT EDIC
Study Year
19. EDIC Findings: Intensive Therapy
and Diabetes Complications
Participants continue to benefit from metabolic
memory of intense glucose control
Intensive therapy aimed at achieving
near normoglycemia:
• Reduces CVD events by more than half
• Should be implemented as early as
possible
DCCT/EDIC N Engl J Med 2005: 353:2643-2653.
20. Cardiovascular Events
Non-Fatal MI, Stroke or CVD Death
0.12
Cumulative Incidence
0.10
Risk reduction 57%
0.08 95% CI: 12, 79
Log-rank P = 0.018
0.06
Conventional
0.04
0.02
Intensive
0.00
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Years from Study Entry
Number at Risk
Intensive: 705 686 640 118
Conventional: 721 694 637 96
21. United Kingdom Prospective Diabetes
Study (UKPDS)
Clinical Trial
Looked at intensive management of blood
glucose levels and long term risk-factors
for diabetes complications
UKPDS. BMJ. 2000; 321:405-412.
ukpds
22. HbA1c
cross-sectional, median values
9
Conventional
8
HbA 1c (%)
Intensive
7
6.2% upper limit of normal range
6
0
0 3 6 9 12 15
Years from randomisation
ukpds
23. UKPDS Findings
Mirrored the findings of DCCT in people with
type 2 diabetes—better glucose control reduced
development of microvascular complications
Demonstrated the need for management of high
blood pressure and cholesterol as well as blood
glucose levels .
UKPDS. BMJ. 2000; 321:405-412.
ukpds
24. Any Diabetes Related Endpoint (cumulative )
1401 of 3867 patients (36%)
60%
Conventional (1138)
% of patients with an event
Intensive (2729)
p=0.029
40%
20%
Risk reduction 12%
0% (95% CI: 1% to 21%)
0 3 6 9 12 15
Years from randomisation
ukpds
25. UKPDS Findings
Risk reduction with 1% decline in annual mean A1C
P <.0001 P = .035 P = .021 P = .0001
0%
12%
14%
16%
15% 19%
30% 37%
43%
45% Micro- PVD MI Stroke Heart Cataract
vascular Failure Extraction
Disease
Stratton IM, et al. BMJ. 2000;321:405-412.
ukpds
26. Largest study in type 2 diabetes
ADVANCE
11,140 patients
20 countries
215 centers
27. 2 x 2 factorial design
Intensive glucose Standard glucose
control control
Routine Routine
BP lowering therapy BP lowering therapy
Intensive glucose Standard glucose
control control
Placebo Placebo
28. Randomized study treatments
• Glucose lowering
Sulfonylurea (gliclazide MR) based
intensive therapy targeting HbA1c of
6.5% versus usual guideline-based
care
29. Randomized glucose lowering strategies
• Intensive control arm
Gliclazide MR (sulfonylurea) in all participants
Unrestricted additional therapy to achieve target
HbA1c 6.5%
• Standard control arm
Sulfonylurea other than Gliclazide MR
Unrestrictedadditional therapy according to
standard local guidelines
• All other treatment
At discretion of treating physician
30. Primary study outcomes
Macrovascular
– Non-fatal stroke, non-fatal myocardial infarction or
death from any cardiovascular cause (including
sudden death)
Microvascular
– New or worsening nephropathy or diabetic eye disease
Composite of macrovascular and
microvascular outcomes
31. Hemoglobin A1c
10.0 Standard
9.5 Intensive
9.0
Mean HbA1c
8.5
Mean HbA1c (%)
at final visit
8.0
7.5
7.3 %
7.0 Ä 0.67% (95% CI 0.64 - 0.70); p<0.001
6.5 6.5%
6.0
5.5
5.0
0 6 12 18 24 30 36 42 48 54 60 66
Follow-up (Months)
37. ACCORD TRIAL
Rate of death from any cause and from cardiovascular
causes were significantly higher in the intensive-
therapy group than in the standard-therapy group
Nonfatal myocardial infarction was significantly lower
in the intensive-therapy group
Nonfatal stroke and either fatal or nonfatal congestive
heart failure did not differ significantly between the two
groups
The benefits of intensive therapy appear after
prolonged treatment (3 yrs)
38. ACCORD TRIAL
• 19 of the 41 excess deaths from CV causes in
this study could be due to or related to
hypoglycemia
• Few patients in the ACCORD trial met the
treatment goal of below 6% of HbA1C
40. ACCORD demonstrated increase in
MORTALITY with intensive treatment
Increase all cause mortality (events)
with Intensive therapy of ACCORD
N Engl J Med 2008;358:2560-72
41. Results…. Increased mortality in
ACCORD study
*
40 *=significant
35
*
30
22 Increased deaths seen
20
Hazard rat io ( % )
in ACCORD study
10
0
-10 -7
-12
-20
-21
-30
Any deat h CV deat h Nephropat hy
ACCORD ADVANCE
N Engl J Med 2008;358:2545-59.; N Engl J Med 2008;358:2560-72.
43. ACCORD, ADVANCE, and VADT
Lessons Learned
• Intensive glucose control does not reduce CVD
mortality in T2DM, and may increase risk,
especially in patients with pre-existing CHD
• Aggressive A1c targets (<6.5%) were associated
with a 3-fold increased risk hypoglycemia
• No excess CVD Mortality was seen with
Rosigliatazone
44. ACCORD, ADVANCE, and VADT
Lessons Learned- Continued
• Intensive control associated with reduced risk for
nephropathy in ADVANCE.
• To reach and maintain A1c targets of <6.5
required frequent adjustments of multiple anti-
diabetic medications
• Aggressive Targets (<6.5) are probably
reasonable for healthy patients to reduce risk
micro-vascular complications
53. ADA Evidence Grading System for
Clinical Recommendations
Level of
Evidence Description
A Clear or supportive evidence from adequately
powered well-conducted, generalizable,
randomized controlled trials
B Supportive evidence from well-conducted cohort
studies or case-control study
C Supportive evidence from poorly controlled or
uncontrolled studies
Conflicting evidence with the weight of evidence
supporting the recommendation
E Expert consensus or clinical experience
ADA. Diabetes Care 2011;34(suppl 1):S12. Table 1.
54. Criteria for the Diagnosis of Diabetes
A1C ≥6.5%
OR
Fasting plasma glucose (FPG)
≥126 mg/dl (7.0 mmol/l)
OR
Two-hour plasma glucose ≥200 mg/dl
(11.1 mmol/l) during an OGTT
OR
A random plasma glucose ≥200 mg/dl
(11.1 mmol/l)
ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.
Slide 1. Increased Risk of Heart Disease in Diabetes The impact of heart disease on people with diabetes is significant. Nearly 75% of deaths among diabetics are directly attributable to CHD, 1 and type 2 diabetes is associated with a two- to fourfold increased risk of CHD. 2 In addition, results from a Finnish study showed that the 1-year mortality rate following an MI was higher in diabetic men (44%) compared with nondiabetic men (33%) and in diabetic women (37%) compared with nondiabetic women (20%). 3 In absolute terms, a 50-year-old individual with diabetes and without clinical evidence of macrovascular disease has approximately a 20% risk of mortality due to cardiovascular disease and about a 15% risk of a nonfatal MI within a 10-year period. 4,5 Cardiovascular complications are the most significant cause of health care expenditures in people with diabetes. 6 A major challenge in the treatment of patients with diabetes is to reduce the risk of cardiovascular disease. References 1. Bierman EL. Arterioscler Thromb. 1992;12:647-656. 2. American Diabetes Association. Diabetes Care . 2000;23(suppl 1):S57-S60. 3. Miettinen H, et al. Diabetes Care . 1998;21:69-75. 4. Hanefeld M, et al. Diabetologia. 1996;39:1577-1583. 5. Turner RC, et al. Diabetologia. 1997;40(suppl 2):S121-S122. 6. Carpentier A, Lewis GF. Can J Diabetes Care. 1998;22:28-38.
The Multiple Risk Factor Intervention Trial (MRFIT) sought to assess predictors of mortality from CVD and determine whether diabetes is an independent risk factor for CVD mortality. The study population included men aged 35 to 57 years with or without diabetes who had been screened for risk factors for CVD. In addition to diabetes, risk factors included high serum cholesterol, systolic blood pressure elevation, and cigarette smoking. Of the 1,092 deaths that occurred during an average 12-year follow-up among 5,163 men who were taking antidiabetic medications, 603 were attributable to CVD. Over the same follow-up period, 20,867 deaths occurred among 342,815 men who were not taking antidiabetic agents, and 8,965 were attributed to CVD. In men with diabetes, the absolute risk of death from CVD was greater for all age strata, ethnicity, and risk factor levels. When adjusted for age, race, income level, serum cholesterol, systolic blood pressure, and number of cigarettes smoked each day, the relative risk for CVD and CHD was 3.0 and 3.2 times higher, respectively ( P <0.0001), for men with diabetes. Stamler J, et al. Diabetes Care. 1993;16:434-444.
This population-based study compared the 7-year incidence of fatal and nonfatal MI among subjects with and without type 2 diabetes. A history of MI at baseline in either group was significantly associated with an increased incidence of fatal and nonfatal MI ( P <0.001). Subjects with neither diabetes nor prior MI had the best prognosis (3.5% incidence of MI); subjects with both diabetes and prior MI had the worst prognosis (45% incidence of MI). Those patients with type 2 diabetes and no prior history of MI had intermediate survival rates, similar to patients without diabetes but with a history of MI (20.2% and 18.8%, respectively, after adjustments for age and sex). Coronary disease incidence rates were also similar between these two groups. These findings suggest that all patients with diabetes should be treated as if they had prior MI, ie, should be treated aggressively. Haffner SM, et al. N Engl J Med . 1998;339:229–234.
C (core) represents a core slide in this curriculum. Diabetes Doubles Risk for MI Mortality Despite Advances in Cardiac Care Heart disease was a major cause of mortality in the early part of the 20th century and by mid-century accounted for greater than half of all deaths in the United States. As illustrated in the slide, developments in cardiac care have significantly reduced mortality from myocardial infarction (MI).The advances in cardiac care can be categorized into several phases based on key discoveries and implementation of novel practices. The introduction of cardiac care units (CCU) during the early 1960s significantly decreased the in-hospital mortality from MI. The subsequent development of thrombolytic therapies during the so-called “lytic era,” along with the development of additional reperfusion techniques, was successful in further reducing MI mortality. Novel recent developments, including the use of statin drugs, have further reduced MI mortality. Concomitant with these decreases in overall MI mortality, there has been a significant reduction in the number of MI deaths in patients with diabetes. However, survey of the literature demonstrates that individuals with diabetes still demonstrate an elevated risk for mortality due to MI. Recent studies have elucidated novel risk factors for MI and diabetes. Hence, the further reduction of death due to MI will need to target these risk factors as well as the development of novel methods, devices, and molecular approaches to the diseases themselves. Braunwald E. N Engl J Med . 1997;337:1360-1369.
C (core) represents a core slide in this curriculum. Diabetes and Heart Failure: Current Knowledge Numerous studies have demonstrated that diabetes is a major risk factor for heart failure (HF). The development of a diabetic cardiomyopathy, a process that results in structural abnormalities in the myocardium of patients with diabetes, leads to both systolic and diastolic dysfunction and ultimately to HF. This can occur even in the absence of other risk factors. The mechanisms responsible for the development of the cardiomyopathy are not clear but include the generation of toxic end-products and differential gene expression. It is likely that development of diabetic HF is multifactorial and include the production of reactive oxygen species, advanced glycation end-products, increased free fatty acid turnover, and differential gene expression. However, additional research is required to further elucidate the true causes and exact mechanisms. SOLVD=Studies of Left Ventricular Dysfunction. HOPE=Heart Outcomes Prevention Evaluation. CHS=Cardiovascular Health Study. Piccini JP et al. Am J Med . 2004;116(suppl 5A):64S-75S. Trost S, LeWinter M. Curr Treat Options Cardiovasc Med . 2001;3:481-492.
Relation of Glucose Tolerance Status to LVM Henry and colleagues monitored the changes in left ventricular mass (LVM) to determine whether there was an association with glucose tolerance status and to determine whether arterial stiffness, atherosclerosis, and flow-mediated dilation play a role in any changes in LVM. The study population (n=780) consisted of individuals with normal glucose metabolism (n=287), impaired glucose metabolism (n=179), or type 2 diabetes (n=314). Results indicated that LVM increased significantly with deteriorating glucose tolerance status in women but not in men. This increase in LVM was found to be independent of arterial stiffness, atherosclerosis, and flow-mediated dilation. Rutter and colleagues examined the relationship between changes in LV parameters and glucose tolerance status. The study group consisted of 2,623 subjects (1,514 women and 1,109 men) from the Framingham Heart Study who were free of MI and heart failure. This study found that the severity of hyperglycemia was more strongly correlated to LVM in women than men. In addition, multivariate analysis indicated a correlation between increased LVM and insulin resistance in women but not in men. Henry RMA et al. Diabetes Care . 2004;27:522-529. Rutter MK et al. Circulation . 2003;107:448-454.
The Diabetes Control and Complications Trial (DCCT), an NIH-funded clinical trial, was conducted from 1983 to 1993. The DCCT is the largest, most comprehensive diabetes study ever conducted. The study compared the effects of two treatment regimens—standard therapy and intensive control—on the complications of diabetes. Reference The DCCT Study Research Group. New England Journal of Medicine, 329(14), September 30, 1993.
The DCCT showed that tight glucose control slows the onset and progression of the microvascular complications of diabetes—eye, kidney, and nerve diseases. In fact, it showed that any sustained lowering of blood glucose helps, even if the person has a history of poor control. Reference The DCCT Study Research Group. New England Journal of Medicine, 329(14), September 30, 1993.
Study results showed that keeping blood glucose levels as close to normal as possible lowered the risk of: Eye disease by 76% Kidney disease by 50% Nerve disease by 60% Reference The DCCT Study Research Group. New England Journal of Medicine, 329(14), September 30, 1993.
The Epidemiology of Diabetes Interventions and Complications Study (EDIC) is an ongoing observational study that began in 1994 and follows participants previously enrolled in the Diabetes Control and Complications Trial (DCCT). The EDIC study determined whether the use of intensive therapy, as compared to conventional therapy during the time period people were enrolled in the DCCT, affected the long-term incidence of cardiovascular disease. Reference The DCCT/EDIC Study Research Group. New England Journal of Medicine, 353:2643-2653, December 22, 2005.
EDIC findings are compelling: • More than a decade after the DCCT was concluded, study participants are still benefiting from what appears to be a metabolic memory of their approximately 6.5 years of intense glucose control. • Intensively treated patients had less than half the number of cardiovascular (CVD) events than the conventionally treated group. • Such events included heart attacks, stroke, angina, and coronary artery disease requiring angioplasty of coronary bypass surgery. • Researchers conclude that glucose control should be started as early as possible to delay or prevent serious CVD complications. Reference The DCCT/EDIC Study Research Group. New England Journal of Medicine, 353:2643-2653, December 22, 2005.
The United Kingdom Prospective Diabetes Study (UKPDS) was a 20 year clinical trial co-coordinated by the Diabetes Research Laboratories at Oxford. The UKPDS was designed to determine whether intensive management of type 2 diabetes in controlling blood glucose levels resulted in a reduction in long term diabetes complications compared with standard care. Reference Stratton IM, Et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000; 321:405-412.
UKPDS mirrored the findings of the DCCT in people with type 2 diabetes – also showing that tighter blood glucose control reduced the development of diabetes complications. The UKPDS also demonstrated the need for management of high blood pressure (hypertension) and cholesterol (dislipidemia) in addition to blood glucose levels. So, controlling the ABCs of diabetes (A1C, Blood Pressure, and Cholesterol) can reduce the development of diabetes complications. Reference Stratton IM, Et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000; 321:405-412.
In the UKPDS, each 1% decrease in annual mean A1C level reduced the risk of microvascular complications by 37%, peripheral vascular disease (PVD) by 43%, myocardial infarction (MI) by 14%, stroke by 12%, heart failure by 16%, and cataract extraction by 19%. These data indicate that over time there is a quantifiable relationship between the risk of complications of diabetes and glycemia. Reference Stratton IM, Adler, AI, Neil HA, et al. Association of glycemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000; 321:405-412.
The Veterans Affairs Diabetes Trial (VADT) randomized participants with type 2 diabetes uncontrolled on insulin or maximal dose oral agents (median entry A1C 9.4%) to a strategy of intensive glycemic control (goal A1C 6.0%) or standard glycemic control, with a planned A1C separation of at least 1.5% 1 Medication treatment algorithms were used to achieve the specified glycemic goals, with a goal of using similar medications in both groups; other CVD risk factors were treated aggressively and equally in both groups Median A1C levels of 6.9 and 8.4% were achieved in the intensive and standard arms, respectively, within the first year of the study; the primary outcome was a composite of CVD events; cumulative primary outcome was nonsignificantly lower in the intensive arm The evidence for a cardiovascular benefit of intensive glycemic control primarily rests on long-term follow-up of study cohorts treated early in the course of type 1 and type 2 diabetes and subset analyses of ACCORD, ADVANCE, and VADT. A recent group-level metaanalysis of the latter three trials suggests that glucose lowering has a modest (9%) but statistically significant reduction in major CVD outcomes, primarily nonfatal MI, with no significant effect on mortality A prespecified subgroup analysis suggested that major CVD outcome reduction occurred in patients without known CVD at baseline (HR 0.84 [95% CI 0.74– 0.94]). 2 Conversely, the mortality findings in ACCORD and subgroup analyses of VADT suggest that the potential risks of very intensive glycemic control may outweigh its benefits in some patients, such as those with very long duration of diabetes, known history of severe hypoglycemia, advanced atherosclerosis, and advanced age/frailty References Duckworth W, Abraira C, Moritz T, et al., for the VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-139. Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009;52:2288–2298.
OL (off-label) indicates that one or more drugs in the slide reflect non FDA-approved use or are investigational in nature. Steno-2: Study Design Danish researchers conducted a randomized, open, parallel study comparing the effect of a targeted, intensified, multifactorial intervention versus conventional intervention on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. Mean follow-up was 7.8 years. Primary endpoint was a composite of death from cardiovascular causes, nonfatal stroke, nonfatal myocardial infarction, revascularization, and amputation as a result of ischemia. Secondary endpoints consisted of indicators of microvascular disease, including incidence of diabetic nephropathy and/or the development or progression of diabetic retinopathy or neuropathy. Gæde P et al. N Engl J Med. 2003;348:383-393.
OL (off-label) indicates that one or more drugs in the slide reflect non FDA-approved use or are investigational in nature. Steno-2: Multifactorial Intervention and CV Events in Type 2 Diabetes In the Steno-2 Study, intensive, target-driven therapy aimed at multiple risk factors reduced the risk of cardiovascular events by about 50% in patients with type 2 diabetes and microalbuminuria. This slide shows Kaplan-Meier estimates of the composite study endpoint, which consisted of nonfatal myocardial infarction, death from cardiovascular causes, coronary artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation, and surgery for peripheral atherosclerotic artery disease. The divergence of the curves suggests that continued intensive therapy may have resulted in an even better prognosis. A course of conventional therapy was completed by 63 patients. Sixty-seven patients completed intensive therapy, which consisted of stepped administration of behavior modification (diet, exercise) and pharmacologic therapy that targeted hyperglycemia (oral hypoglycemic agents, insulin), hypertension (angiotensin-converting enzyme [ACE] inhibitors, angiotensin II-receptor blockers, diuretics, calcium-channel blockers, -blockers), dyslipidemia (statins, fibrates), microalbuminuria, and cardiovascular risk (aspirin). Mean age of all patients in the study was 55 years and mean follow-up was 7.8 years. There were 118 cardiovascular events during follow-up: 85 events in 35 conventionally treated patients and 33 events in 19 intensively treated patients. Nephropathy developed in 31 conventionally treated patients and in 16 intensively treated patients, retinopathy in 51 conventionally treated patients and in 38 intensively treated patients, and neuropathy in 43 conventionally treated patients and in 24 intensively treated patients. Compared with the conventionally treated group, the risk ratios for the intensive-therapy group were 0.47 for cardiovascular disease, 0.39 for nephropathy, 0.42 for retinopathy, and 0.37 for neuropathy. Gaede P et al. N Engl J Med . 2003;348:383-393.
“ Standards of Medical Care in Diabetes—2011” contains all of the current and key clinical recommendations of the American Diabetes Association (ADA) These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to affect health outcomes of patients with diabetes favorably The slides are organized to correspond with sections within the “Standards of Medical Care in Diabetes—2011” While not every section in the document is represented, these slides do incorporate the most salient points from the Position Statement These standards of care are revised annually by the ADA’s multidisciplinary Professional Practice Committee, incorporating new evidence; subsequently, they are reviewed and approved by the Executive Committee of ADA’s Board of Directors Reference American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011;34(suppl 1):S11-12. Available online at http://care.diabetesjournals.org/content/34/Supplement_1
The American Diabetes Association has developed a grading system for clinical recommendations (Table 1) This grading system was used to clarify and codify evidence that forms the basis for each of the recommendations in the “Standards of Medical Care in Diabetes—2011” The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E This slide summarizes the description for each of these levels of evidence Reference American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011;34(suppl 1):S12. Table 1.
Table 2, current diagnostic criteria for the diagnosis of diabetes, is divided into five slides On this slide, all four criteria are included: A1C ≥6.5% Fasting plasma glucose (FPG) ≥126 mg/dl (7.0 mmol/l) Two-hour plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT A random plasma glucose ≥200 mg/dl (11.1 mmol/l), in patients with classic symptoms of hyperglycemia or hyperglycemic crisis The subsequent slides examine each of the four criteria in greater detail Reference American Diabetes Association. Standards of medical care in diabetes—2011. Diabetes Care 2011;34(suppl 1):S13. Table 2.