Plasma glucose and prediction of microvascular disease and mortality: evaluation of 1997 American Diabetes Association and 1999 World Health Organization criteria for diagnosis of diabetes

OBJECTIVE: The 1997 American Diabetes Association (ADA) and 1999 World Health Organization (WHO) criteria for diabetes and hyperglycemia were evaluated and compared with respect to prediction of microvascular and macrovascular disease and mortality RESEARCH DESIGN AND METHODS: The prevalence of retinopathy and nephropathy at baseline and during the subsequent 10 years and mortality rates were examined in relation to baseline fasting plasma glucose (FPG) and 2-h postload plasma glucose (2-h PG) among 5,023 Pima Indian adults and in relation to the cut points defined by the ADA and WHO criteria. RESULTS: The frequencies of retinopathy and nephropathy were directly related to baseline FPG and 2-h PG with approximate thresholds near or below the current diagnostic criteria for diabetes (FPG > or =7.0 and 2-h PG > or = 11.1 mmol/l). The rates of retinopathy were 4.7% in impaired fasting glucose (IFG) and 20.9% in diabetes by ADA criteria; 1.6% for impaired glucose tolerance (IGT) and 19.7% for diabetes by 1985 WHO criteria; and 1.2% for IGT and 19.2% for diabetes by the 1999 WHO criteria. Mortality rates from cardiovascular-renal-related diseases were higher in diabetic individuals (FPG > or =7.0 or 2-h PG > 11.1 mmol/l) than in those with normal FPG and 2-h PG but were not elevated in those with IFG or IGT. CONCLUSIONS: Retinopathy and nephropathy were directly related to higher FPG or 2-h PG. FPG, which identifies those at high risk of microvascular disease and mortality, can be used to predict these outcomes and to diagnose diabetes when oral glucose tolerance testing is not practical.     

Relationships of fasting and postload glucose levels to sex and alcohol consumption. Are American Diabetes Association criteria biased against detection of diabetes in women?

OBJECTIVE: To compare, in men and women, the prevalence of undiagnosed type 2 diabetes assessed using criteria from the American Diabetes Association (ADA) and the World Health Organization (WHO) and to investigate risk factors associated with fasting and 2-h postload plasma glucose. RESEARCH DESIGN AND METHODS: Data from two companion surveys of Europeans, South Asians, and Afro-Caribbeans in west London were used. A total of 4,367 men and women aged 40-64 years who were not known to have diabetes underwent an oral glucose tolerance test after an overnight fast. The prevalence of undiagnosed diabetes was estimated using the ADA (fasting plasma glucose > or = 7.0 mmol/l) and WHO (2-h postload glucose > or = 11.1 mmol/l) criteria for epidemiologic studies. The association of body fat and usual alcohol intake with plasma glucose and diabetes prevalence was assessed. RESULTS: Compared with the WHO criterion, the ADA criterion gave a higher prevalence of diabetes in men (6.4 vs. 4.7%) but a lower prevalence in women (3.3 vs. 4.2%). In Afro-Caribbeans, the sex difference in diabetes prevalence was reversed. Women had significantly lower fasting glucose than men despite higher 2-h glucose levels. Alcohol intake was positively associated with fasting glucose in men and women but not with 2-h glucose levels. CONCLUSIONS: The new ADA criterion, based on fasting glucose alone, does not take account of sex differences in metabolic response to fasting or possible artifactual effects on fasting glucose. With the ADA criterion, alcohol intake was a significant risk factor for diabetes in our study population; this was not the case with the WHO criterion.     

The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes

OBJECTIVE: The 1997 American Diabetes Association (ADA) and the 1985 and 1999 World Health Organization (WHO) criteria for diabetes and hyperglycemia differ. The appropriateness of these diagnostic criteria in terms of individuals identified as abnormal and their prognosis has been debated. The purpose of this study is to compare the classifications of people by these criteria and to compare fasting and postload plasma glucose concentrations in the prediction of diabetes. RESEARCH DESIGN AND METHODS: The frequencies of diabetes by the 3 sets of criteria were compared in 5,023 adult Pima Indians not taking hypoglycemic drugs. Among nondiabetic subjects, fasting plasma glucose (FPG) and 2-h postload plasma glucose (2-h PG) concentrations and categories of impaired glucose regulation or diabetes were evaluated as predictors of diabetes defined by 1999 WHO criteria. RESULTS: The frequency of diabetes was 12.5% by 1997 ADA criteria, 14.6% by 1985 WHO criteria, and 15.3% by 1999 WHO criteria. The incidence of diabetes was strongly related to higher FPG and 2-h PG, each of which had very similar predictive powers. Impaired glucose tolerance (IGT) was more common than impaired fasting glucose (IFG) (15 vs. 5%), but the 5-year incidence of diabetes was higher in IFG than IGT (37 vs. 24%). CONCLUSIONS: The prevalence and incidence of diabetes are somewhat lower with the ADA criteria than with the 1985 or 1999 WHO criteria. The intermediate categories of glycemia differ substantially IFG defines a smaller number of people who are at higher risk of developing diabetes than those with IGT. More people at high risk of diabetes could be identified by using either IFG or IGT, as recommended by the 1999 WHO criteria, or by using the FPG concentration alone, but with a lower cutoff value.     

Implications of new diagnostic criteria for abnormal glucose homeostasis in women with previous gestational diabetes.

OBJECTIVE: To determine the consequences of applying revised American Diabetes Association (ADA) (1997) and World Health Organization (WHO) (1998) recommendations for the classification of glucose intolerance in women with previous gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: There were 192 women with previous GDM who took an oral glucose tolerance test (OGTT) 1-86 months after delivery and were classified by WHO (1985), ADA (1997, fasting glucose), and revised WHO (1998) guidelines. RESULTS: Among the 165 women without a preexisting diagnosis of diabetes, WHO-1985 and ADA-1997 provided similar estimates of diabetes prevalence (13.3% vs. 11.5%) but widely differing estimates of impaired glucose homeostasis (31.5% impaired glucose tolerance [IGT] by WHO-1985 vs. 10.9% impaired fasting glucose by ADA-1997 criteria). Overall, 56 women (34%) showed a classification discrepancy between WHO-1985 and ADA-1997 criteria, including 44 with normal fasting glucose by ADA-1997 criteria, but abnormal 2-h glucose by WHO-1985 criteria (40 IGT, 4 diabetes). The cardiovascular risk profile of these women was more favorable than that of 18 women with impaired fasting glucose. WHO-1998 recommendations reproduced ADA-1997 findings when used as a fasting screen, but behaved similarly to WHO-1985 criteria when 2-h glucose values were also analyzed. CONCLUSIONS: All criteria produced similar estimates of diabetes prevalence. However, analyses based on a single fasting glucose screen (and a threshold of 6.1 mmol/l) failed to identify 60% of women with abnormal 2-h glucose levels. Screening women with previous GDM (and by analogy, other groups at high risk of diabetes) with a single fasting glucose has low sensitivity for the detection of abnormal glucose tolerance. Recent guidelines recommending this approach require reevaluation.     

Gestational diabetes mellitus diagnosed with a 2-h 75-g oral glucose tolerance test and adverse pregnancy outcomes.

OBJECTIVE: To evaluate American Diabetes Association (ADA) and World Health Organization (WHO) diagnostic criteria for gestational diabetes mellitus (GDM) against pregnancy outcomes. RESEARCH DESIGN AND METHODS: This cohort study consecutively enrolled Brazilian adult women attending general prenatal clinics. All women were requested to undertake a standardized 2-h 75-g oral glucose tolerance test (OGTT) between their estimated 24th and 28th gestational weeks and were then followed to delivery. New ADA criteria for GDM require two plasma glucose values > or = 5.3 mmol/l (fasting), > or = 10 mmol/l (1 h), and > or = 8.6 mmol/l (2 h). WHO criteria require a plasma glucose > or = 7.0 mmol/l (fasting) or > or = 7.8 mmol/l (2 h). Individuals with hyperglycemia indicative of diabetes outside of pregnancy were excluded. RESULTS: Among the 4,977 women studied, 2.4% (95% CI 2.0-2.9) presented with GDM by ADA criteria and 7.2% (6.5-7.9) by WHO criteria. After adjustment for the effects of age, obesity, and other risk factors, GDM by ADA criteria predicted an increased risk of macrosomia (RR 1.29, 95% CI 0.73-2.18), preeclampsia (2.28, 1.22-4.16), and perinatal death (3.10, 1.42-6.47). Similarly, GDM by WHO criteria predicted increased risk for macrosomia (1.45, 1.06-1.95), preeclampsia (1.94, 1.22-3.03), and perinatal death (1.59, 0.86-2.90). Of women positive by WHO criteria, 260 (73%) were negative by ADA criteria. Conversely, 22 (18%) women positive by ADA criteria were negative by WHO criteria. CONCLUSIONS: GDM based on a 2-h 75-g OGTT defined by either WHO or ADA criteria predicts adverse pregnancy outcomes.     

Prevalence of undiagnosed diabetes in three American Indian populations. A comparison of the 1997 American Diabetes Association diagnostic criteria and the 1985 World Health Organization diagnostic criteria: the Strong Heart Study

OBJECTIVE: In 1997, the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association (ADA) recommended three new sets of criteria for the diagnosis of diabetes that were different from those established by the World Health Organization (WHO) in 1985. One of these three methods was based on a fasting plasma glucose value only. This article compares ADA criteria with WHO criteria by applying them to three subgroups of American Indians in the Strong Heart Study who had no known diabetes. RESEARCH DESIGN AND METHODS: The Strong Heart Study is a prospective epidemiological study of vascular disease in three American Indian populations aged 45-74 years. During the baseline examination from 1988 to 1991, participants without diagnosed diabetes underwent a fasting glucose test and a 2-h oral glucose tolerance test. These values were used to compare the ADA and WHO diagnostic criteria. RESULTS: By using fasting and 2-h glucose values, prevalence rates of undiagnosed diabetes were 15.9% according to WHO criteria and 14.4% according to ADA criteria. The overall agreement rate was 65%, and the weighted kappa statistic was 0.474, which indicates moderate agreement. The age-specific analysis showed that, among participants between 45 and 54 years of age, the prevalence rates of undiagnosed diabetes were 13.4% according to WHO criteria and 12.7% according to ADA criteria. Among those aged 55-74 years, the rates were 18.7% according to WHO criteria and 16.3% according to ADA criteria. Thus, the difference in the prevalence rates when using WHO and ADA criteria, although generally small in this population, was three times higher in the older group (2.4%) than the difference in the younger group (0.7%). CONCLUSIONS: The Strong Heart Study found that prevalence rates of undiagnosed diabetes determined by ADA criteria and WHO criteria were similar in its American Indian population. The data suggest that the difference between the two criteria may increase as age increases. Longitudinal data will be needed to evaluate further the utility of the two criteria.     

Prandial glucose regulation and cardiovascular disease in Type 2 diabetes

Type 2 diabetes is associated with an increased risk for cardiovascular disease. In recent years, prospective studies have indicated that, in addition to conventional risk factors, glycaemic control of diabetes predicts cardiovascular disease in both middle-aged and elderly patients with Type 2 diabetes. However, there are no consistent data from different studies to indicate that postprandial glucose is a better predictor for cardiovascular risk than fasting glucose level. Although no clinical trials are available to show that improving glycaemic control prevents cardiovascular mortality and morbidity, recent studies imply that hyperglycaemia in patients with Type 2 diabetes should be treated more intensively than recommended by current guidelines     

One-hour post-load glucose improves the prediction of cardiovascular events in the OPERA study

BackgroundTo estimate the ability of fasting, 1-h, and 2-h post-load glucose to predict cardiovascular outcomes.MethodsWe examined a population-based study consisting of 977 middle-aged subjects who underwent an oral glucose tolerance test with glucose values measured at 0, 60, and 120 min. Participants were followed up to 24 years, and cardiovascular outcomes were collected from national registers. Predictive abilities of fasting, 1-h, and 2-h glucose were evaluated alone and in the prediction models with traditional cardiovascular risk factors using Cox proportional hazard models, the likelihood-ratio test, Harrell''s concordance index and integrated discrimination improvement.ResultsCardiovascular endpoint occurred in 222 (22.7%) participants during a median follow-up of 19.8 years. In the prognostic models, 1-h glucose (HR 1.67, 95%CI 1.10–2.53), but not fasting or 2-h glucose, predicted cardiovascular events statistically significantly. In addition, when adding glucose parameters into the model including traditional cardiovascular risk factors, only 1-h glucose improved the predictive ability (LR-test p=.046). Finally, 1-h glucose found slightly over 50% more cardiovascular endpoints that were not recognized by fasting or 2-h glucose levels.ConclusionsOur findings support the earlier ones suggesting that 1-h glucose would be a better long-term predictor of cardiovascular morbidity and mortality than fasting or 2-h glucose.

KEY MESSAGES

1. In addition to conventional CV risk factors,1-h but not fasting or 2-h post-load glucoses seems to be an independent predictor of cardiovascular events and seems to improve the predictive ability of the traditional cardiovascular risk model.
2. Elevated 1-hpost-load glucose finds a large number (slightly over 50%)of cardiovascular endpoints that were not recognized by fasting or 2-h post-load glucose levels.
3. One-hour glucose seems to be a better long-term predictor of cardiovascular morbidity and mortality than fasting or 2-h post-load glucose.

     

Prevalence-dependent decision limits for the early detection of type 2 diabetes mellitus in venous blood, venous plasma and capillary blood during glucose challenge.

BACKGROUND: The glycemia decision limits recommended by WHO/ADA for type 2 diabetes detection are derived from clinical signs in advanced stages of the disease. Since insulin secretion patterns and sensitivitity are impaired at the beginning of type 2 diabetes, this stage may be better suited to identify decision limits with higher diagnostic efficiency than those currently applied. METHODS: Oral glucose tolerance tests were performed in 300 subjects. Glucose concentrations were measured at 30-min intervals in venous plasma, venous blood and capillary blood. Insulin concentrations in venous plasma, an insulin sensitivity index and body mass index were used to indicate a type 2 diabetic state. A multiple logistic regression procedure was "trained" using only subjects "clearly" considered to be non-diseased or diseased based on an oral glucose tolerance test according to WHO criteria. This insulin algorithm was applied to the whole study group, leading to definitive classification into the non-diseased or the diseased group. This a posteriori classification was used to identify cutoff values with the highest diagnostic efficiency. RESULTS: The diagnostic efficiency was significantly higher when decision limits lower than the WHO recommendations for glucose concentrations were applied in a preselected subpopulation and in all three sample systems tested, e.g., 9.49 mmol/L (171 mg/dL) for venous plasma and 8.94 mmol/L (161 mg/dL) for capillary blood in the 2-h post-load state. The optimized and WHO 2-h cutoff values corresponded to a disease prevalence of 28% and approximately 5% (20% in the fasting state), respectively. Diagnostic efficiency was higher in the 2-h post-load than in the fasting state. Combining fasting values with 2-h post-load values did not further improve the diagnostic efficiency. Glucose concentrations determined from capillary blood were as efficient as those from venous blood or plasma. The number of diabetic subjects detected differed considerably between capillary blood and venous plasma for the WHO/ADA cutoff values, but not for the optimized cutoff values. CONCLUSIONS: The efficiency of type 2 diabetes diagnosis can be improved by optimizing cutoff values according to disease prevalence. Unexpectedly, the optimized 2-h post-load cutoff was lower for capillary blood than for venous plasma. It is proposed to identify a risk group e.g., by characteristics of the metabolic syndrome in which the 2-h post-challenge concentration is determined using lower cut-off values than presently recommended.     

Similar 9-year mortality risks and reproducibility for the World Health Organization and American Diabetes Association glucose tolerance categories: the Hoorn Study

OBJECTIVE: To compare the risks of all-cause and cardiovascular disease (CVD) mortality in the American Diabetes Association (ADA) and World Health Organization (WHO) glucose tolerance categories after 9 years of follow-up in the Hoorn Study and to study the test-retest reproducibility of those categories. RESEARCH DESIGN AND METHODS: In this population-based cohort study of 2,468 elderly men and women, subjects were classified according to both the WHO and the ADA criteria. Causes of death were extracted from the medical records. Age- and sex-adjusted relative risks were estimated by Cox's proportional hazards model. Reproducibility of the diagnostic criteria was assessed in a sample of 1,109 subjects with duplicate oral glucose tolerance tests. RESULTS: Subjects with known diabetes had a four to five times higher risk of all-cause and CVD mortality compared with normal subjects (P<0.05). The relative risks of all-cause mortality were 1.67 (95% CI 1.09-2.57) and 1.56 (1.00-2.43) for newly diagnosed diabetic subjects according to the WHO and ADA criteria, respectively. The WHO and ADA criteria had similar levels of reproducibility The overall K was 0.59 (0.54-0.64) for WHO criteria and 0.61 (0.56-0.66) for ADA criteria. For the category of newly diagnosed diabetes according to WHO or ADA, the percentages of agreement for the second test compared with the first test were 77% (85/110) and 74% (74/100), respectively. CONCLUSIONS: Both sets of diagnostic criteria identify criteria-specific diabetic subjects with an increased mortality risk compared with normal subjects, and the reproducibility of both criteria is similar.     

Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes Study.

OBJECTIVE: To identify risk factors for incident coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: A total of 175 Japanese-American men without CHD were followed for up to 10 years. Baseline variables were blood pressure, weight, BMI, fat areas by computed tomography, skinfold thicknesses, abdominal circumference, plasma insulin, C-peptide, cholesterol, LDL cholesterol, HDL cholesterol, HDL2 cholesterol, and HDL3 cholesterol, triglycerides, apoproteins A1 and B, and diagnosis of diabetes and hypertension. CHD was diagnosed by electrocardiogram and clinical events. Logistic regression was used to estimate odds ratio. RESULTS: There were 50 incident cases of CHD. Using univariate logistic regression analysis, significant risk factors were intra-abdominal fat (P = 0.0090), fasting glucose (P = 0.0002), 2-h glucose (P = 0.0008), fasting HDL cholesterol (P = 0.0086), fasting HDL2 cholesterol (P = 0.030), fasting HDL3 cholesterol (P = 0.018), fasting triglycerides (P = 0.013), systolic (P = 0.0007) and diastolic blood pressure (P = 0.0002), and presence of diabetes (P = 0.0023). Multiple logistic regression models adjusted for BMI and age showed that intra-abdominal fat accounted for the effects of HDL cholesterol or triglycerides. In a multiple logistic regression model that included intra-abdominal fat, all systolic blood pressure and fasting glucose were significant. Substituting diastolic blood pressure for systolic blood pressure and 2-h glucose or diabetes status for fasting glucose produced similar results. CONCLUSIONS: Visceral adiposity, blood pressure, and plasma glucose are important independent risk factors for incident CHD in this population of diabetic and nondiabetic Japanese-American men.     

Hyperglycaemia: link to excess mortality

Asymptomatic diabetes is defined by chronic hyperglycaemia. The 2-h post-challenge glucose level is not generally used in practice and consequently not recommended for diagnosis, so diabetes is defined from fasting hyperglycaemia. Several large studies have been used to evaluate the impact of different diagnostic definitions on the risk of premature death. Meta-analysis of component studies in the Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) study showed that for all-cause mortality fasting glucose did not carry an independent risk but the 2-h post-challenge glucose carried a significant risk after adjusting for factors including fasting glucose. Increasing fasting glucose also did not carry a significant excess risk for cardiovascular mortality but there was an overall significant relative risk with increasing 2-h post-challenge glucose. Analysis of 20-year follow-up data from the combined Whitehall, Paris and Helsinki studies demonstrated that after adjusting for other risk factors men in the upper 20 per cent of the 2-h glucose distribution and those in the upper 2.5 per cent for fasting glucose had a significantly higher risk of all-cause mortality compared with men in the lower 80 per cent of each distribution. Analysis of the Paris Prospective study alone showed that all-cause mortality was highest in those with isolated 2-h post-challenge hyperglycaemia. In men without known diabetes there were J-shaped relationships between both fasting and 2-h glucose and all-cause, cardiovascular and cancer mortalities. Fasting and 2-h glucose levels are highly correlated and hyperglycaemia by either definition is undoubtedly a risk factor for premature death, whatever the cause.     

Impact of new diagnostic criteria for diabetes on different populations.

OBJECTIVE: For epidemiological purposes, it has now been recommended that a fasting plasma glucose value of 7.0 mmol/l can be used to diagnose diabetes, instead of a 2-h value of 11.1 mmol/l. This study assesses the impact of making this change on the prevalence of diabetes and on the phenotype of individuals identified. RESEARCH DESIGN AND METHODS: Data were collated from nine population based southern hemisphere studies in which a 75-g oral glucose tolerance test was performed. Comparisons were made between the prevalence derived from fasting values only and the prevalence derived from 2-h values only. Cardiovascular risk was assessed in all individuals. RESULTS: There were 20,624 subjects in the nine surveys of whom 1,036 had previously diagnosed diabetes and 1,714 had newly diagnosed diabetes, according to either fasting or 2-h glucose. The differences in prevalence within each population resulting from changing the diagnostic criteria ranged from +30 to -19% (relative difference) and +4.1 percentage points to -2.8 percentage points (absolute difference). BMI was the most important determinant of disagreement in classification. A total of 31% of those individuals who were diabetic on the fasting value were not diabetic on the 2-h value, and 32% of those with diabetes on the 2-h value were not diabetic on the fasting value. Apart from obesity, there were no differences in cardiovascular risk between those identified by the fasting and the 2-h values. CONCLUSIONS: Changing the diagnostic criteria is likely to have variable and sometimes quite large effects on the prevalence of diabetes in different populations. Furthermore, the fasting criterion identifies different people as being diabetic than those identified by the 2-h criterion.     

Predictive properties of impaired glucose tolerance for cardiovascular risk are not explained by the development of overt diabetes during follow-up

OBJECTIVE: To evaluate the relationship of impaired glucose tolerance (IGT) at baseline to coronary heart disease (CHD) incidence, and cardiovascular disease (CVD) and total mortality at follow-up, and to analyze whether the relationship is independent of the subsequent development of diabetes during follow-up. RESEARCH DESIGN AND METHODS: A baseline screening survey for diabetes was performed in 1987 using a 2-h 75-g oral glucose tolerance test. A total of 1234 men and 1386 women aged 45-64 years, who were free of diabetes at baseline, were followed up for 10 years. During the follow-up, 153 subjects had an incident CHD event, 224 died, and 100 deaths were due to cardiovascular causes. Multivariate adjusted (adjusted for age, sex, waist-to-hip ratio, systolic blood pressure, cholesterol, HDL cholesterol, and smoking) hazard ratio (HR) was estimated using Cox regression analysis. RESULTS: In subjects who had IGT at baseline and who did not progress to diabetes during the follow-up, the multivariate adjusted HR (95% CI) was 1.49 (0.95-2.34) for CHD incidence, 2.34 (1.42-3.85) for CVD mortality, and 1.65 (1.13-2.40) for all-cause mortality. CONCLUSIONS: Baseline IGT was an independent risk predictor for cardiovascular morbidity and mortality and for total mortality, which was not confounded by the subsequent development of overt diabetes.     

Detecting type 2 diabetes by a single post-challenge blood sample.

In the recent American Diabetes Association (ADA)/WHO recommendations, the oral glucose tolerance test (OGTT) was replaced by the measurement of a single fasting glucose concentration with a decision limit for the detection of type 2 diabetes mellitus (DM) reduced. This proposal, however, misses all cases of isolated post-prandial hyperglycaemia. Therefore, a study was undertaken to develop a post-challenge, one-sample mode of diagnosis. OGTT was performed in 240 high-risk subjects who were suspected to suffer from type 2 DM. Glucose concentrations were determined at 30 min intervals in the capillary blood, venous blood and plasma, and insulin was determined in venous plasma only. The test results were classified in non-disease and disease group according to the decision limits recommended by ADA/WHO. Furthermore, the early insulin response and an insulin sensitivity index were used to determine new cut-off values. These were identified as the concentrations demonstrating the highest diagnostic efficiency and were lower than the WHO limits. The 2 h post-load plasma concentration led to higher efficiency at a cut-off value of 9.0 mmol/l glucose (162 mg/dl) compared to concentrations of samples taken in the fasting state, at an earlier time of the OGTT, or in venous and capillary blood. Under this condition, 72 diabetic patients (35%) were detected in the study group (n = 207), whereas only 36 (17%) were found with one sample in the fasting state and 53 (26%) with two samples using the ADA/WHO criteria. Therefore, a single venous plasma sample taken after 2 h post-glucose challenge appeared to be most efficient for the early detection of DM.     

Additional use of glycated hemoglobin for diagnosis of type 2 diabetes in people undergoing coronary angiography reveals a subgroup at increased cardiovascular risk

OBJECTIVE

To study the prognosis of people with newly diagnosed type 2 diabetes as per the American Diabetes Association (ADA) 2010 definition but without diabetes as per the ADA 2009 definition.

RESEARCH DESIGN AND METHODS

A total of 2,002 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study without a history of diabetes were studied.

RESULTS

During the follow-up of a mean duration ± SD of 7.7 ± 2.0 years, 346 people died (202 cardiovascular deaths). Subjects with type 2 diabetes as per the ADA 2009 definition (n = 468) had significantly increased all-cause and cardiovascular mortality compared with people without diabetes as per the ADA 2010 definition (both P ≤ 0.003). Subjects with type 2 diabetes as per the ADA 2010 definition but without diabetes as per the ADA 2009 definition (n = 150) were at significantly increased risk to die of cardiovascular diseases (P = 0.029).

CONCLUSIONS

Use of the ADA 2010 diabetes definition may be instrumental in improving cardiovascular risk stratification in people undergoing coronary angiography.According to the 2009 guidelines of the American Diabetes Association (ADA), subjects with increased fasting glucose (≥126 mg/dL) and/or postchallenge glucose (≥200 mg/dL) are diagnosed with diabetes (1). Using the ADA 2010 criteria, subjects with isolated elevation of glycated hemoglobin ≥6.5% (fasting glucose <126 mg/dL, postchallenge glucose <200 mg/dL) are also considered diabetic individuals (2).Glycated hemoglobin has been associated with macrovascular disease (3–8). Of particular interest, recent data from the Atherosclerosis Risk in Communities (ARIC) study and the Ludwigshafen Risk and Cardiovascular Health (LURIC) study have shown that glycated hemoglobin is a better predictor for all-cause and cardiovascular mortality than fasting glucose (9,10).The objective of the present work in 2,002 LURIC participants was to analyze whether subjects with newly diagnosed type 2 diabetes as per the ADA 2010 definition who would not have received the diagnosis as per the ADA 2009 definition are at increased risk of death from any cause and from cardiovascular diseases (10,11).     

Performance of recommended screening tests for undiagnosed diabetes and dysglycemia.

OBJECTIVE: To evaluate the performance, in settings typical of opportunistic and community screening programs, of screening tests currently recommended by the American Diabetes Association (ADA) for detecting undiagnosed diabetes. RESEARCH DESIGN AND METHODS: Volunteers aged > or =20 years without previously diagnosed diabetes (n = 1,471) completed a brief questionnaire and underwent recording of postprandial time and measurement of capillary blood glucose (CBG) with a portable sensor. Participants subsequently underwent a 75-g oral glucose tolerance test; fasting serum glucose (FSG) and 2-h postload serum glucose (2-h SG) concentrations were measured. The screening tests we studied included the ADA risk assessment questionnaire, the recommended CBG cut point of 140 mg/dl, and an alternative CBG cut point of 120 mg/dl. Each screening test was evaluated against several diagnostic criteria for diabetes (FSG > or =126 mg/dl, 2-h SG > or =200 mg/dl, or either) and dysglycemia (FSG > or =110 mg/dl, 2-h SG > or =140 mg/dl, or either). RESULTS: Among all participants, 10.7% had undiagnosed diabetes (FSG > or =126 or 2-h SG > or =200 mg/dl), 52.1% had a positive result on the questionnaire, 9.5% had CBG > or =140 mg/dl, and 18.4% had CBG > or =120 mg/dl. The questionnaire was 72-78% sensitive and 50-51% specific for the three diabetes diagnostic criteria; CBG > or =140 mg/dl was 56-65% sensitive and 95-96% specific, and CBG > or =120 mg/dl was 75-84% sensitive and 86-90% specific. CBG > or =120 mg/dl was 44-62% sensitive and 89-90% specific for dysglycemia. CONCLUSIONS: Low specificity may limit the usefulness of the ADA questionnaire. Lowering the cut point for a casual CBG test (e.g., to 120 mg/dl) may improve sensitivity and still provide adequate specificity.     

Type 2 diabetes worldwide according to the new classification and criteria

Two major reports have recently revised the classification of and diagnostic criteria for diabetes. Classification was previously based on the need for insulin (insulin-dependent or non-insulin-dependent), but this has become increasingly confusing. Now, the type of diabetes is determined by the etiological process rather than the treatment modality. Type 1 diabetes is thus characterized by islet cell destruction and type 2 diabetes by a combination of defects in insulin secretion and action. An individual with either type of diabetes may be on any treatment modality. This classification should prove to be more logical and, for example, allow latent autoimmune diabetes in adults, which typically does not require insulin at presentation, to be classified as type 1 diabetes. The fasting plasma glucose diagnostic threshold for diabetes has been lowered to 7.0 mmol/l (126 mg/dl), and impaired fasting glucose (fasting plasma glucose 6.1-6.9 mmol/l [110-125 mg/dl]) has been introduced as a new category of intermediate glucose metabolism. These changes recognize that the old fasting threshold did not match the 2-h (postload) threshold well and that both micro- and macrovascular disease develop at lower fasting glucose levels than previously recognized. Although the prevalences of diabetes according to the new fasting and 2-h criteria are now similar in most populations, the actual individuals identified as having diabetes are often different. Over 30% of all those with diabetes have a nondiabetic fasting glucose but still have increased cardiovascular mortality. Thus, it is important to retain the oral glucose tolerance test for the diagnosis of diabetes.     

Abnormal glucose tolerance and increased risk for cardiovascular disease in Japanese-Americans with normal fasting glucose

OBJECTIVE: To compare the American Diabetes Association (ADA) fasting glucose and the World Health Organization (WHO) oral glucose tolerance test (OGTT) criteria for diagnosing diabetes and detecting people at increased risk for cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: Study subjects were 596 Japanese-Americans. Fasting insulin, lipids, and C-peptide levels; systolic and diastolic blood pressures (BPs); BMI (kg/m2); and total and intra-abdominal body fat distribution by computed tomography (CT) were measured. Study subjects were categorized by ADA criteria as having normal fasting glucose (NFG), impaired fasting glucose (IFG), and diabetic fasting glucose and by WHO criteria for a 75-g OGTT as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT). RESULTS: Of 503 patients with NFG, 176 had IGT and 20 had DGT These patients had worse CVD risk factors than those with NGT . The mean values for NGT, IGT, and DGT, respectively, and analysis of covariance P values, adjusted for age and sex, are as follows; intra-abdominal fat area by CT 69.7, 95.0, and 101.1 cm2 (P < 0.0001); total CT fat area 437.7, 523.3, and 489.8 cm2 (P < 0.0001); fasting triglycerides 1.40, 1.77, and 1.74 mmol/l (P = 0.002); fasting HDL cholesterol 1.56, 1.50, and 1.49 mmol/l (P = 0.02); C-peptide 0.80, 0.90, 0.95 nmol/l (P = 0.002); systolic BP 124.9, 132.4, and 136.9 mmHg (P = 0.0035); diastolic BP 74.8, 77.7, and 78.2 mmHg (P = 0.01). CONCLUSIONS: NFG patients who had IGT or DGT had more intra-abdominal fat and total adiposity; higher insulin, C-peptide, and triglyceride levels; lower HDL cholesterol levels; and higher BPs than those with NGT. Classification by fasting glucose misses many Japanese-Americans with abnormal glucose tolerance and less favorable cardiovascular risk profiles.     

Reproducibility of S-insulin and B-glucose responses in two identical oral glucose tolerance tests

Recently, the diagnostic criteria for type 2 diabetes mellitus have been changed, but there are disagreements about which measurements should be used. In contrast to the American Diabetes Association (ADA), The World Health Organization (WHO) still recognizes fasting and 2-h glucose concentrations measured on either plasma or whole blood as diagnostic tools. Insulin sensitivity and insulin secretion are both assumed to be involved in the pathogenesis of type 2 diabetes. The oral glucose tolerance test (OGTT) for estimating insulin sensitivity and secretion is increasingly used, e.g. in intervention trials. The objectives of this study were to estimate the coefficients of intra-individual variation (CVw) of blood glucose and serum insulin concentrations from an OGTT as well as indices of insulin sensitivity (HOMA) and insulin secretion (delta insulin30/delta glucose30) derived from this test. Following duplicate OGTTs with a median interval of 13 days (range 1-87 days), the analytical, inter-individual, and intra-individual coefficients of variation were calculated by nested ANOVA. The CVw for fasting blood glucose (7%) was considerably lower than that for 2-h post-load glucose (15%), which was again lower than for the insulin concentrations and indices of insulin sensitivity and secretion. In conclusion, the intra-individual variation is larger for 2-h post-load glucose than for fasting glucose and may question the continued use of the 2-h post-load glucose value in the diagnosis of type 2 diabetes.