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.     

Comparison of the effect of plasma glucose concentrations on microvascular disease between Pima Indian youths and adults

OBJECTIVE--To examine whether the current adult guidelines for diagnosis of diabetes are applicable to youth (age <20 years). RESEARCH DESIGN AND METHODS--We analyzed fasting plasma glucose (FPG) and 2-h plasma glucose (PG) in two groups of Pima Indians, youths aged 5-19 years and adults aged 20-34 years, in relation to the incidence of microvascular disease when subjects were reexamined at ages 25-39 (youths) and 40-54 (adults). Microvascular disease was defined as retinopathy or a urine protein-to-creatinine ratio > or =0.5 g. RESULTS--An increase in the incidence of microvascular disease occurred at nearly the same level of glycemia in both groups. For youths, this increase occurred at FPG approximately 7.3 mmol/l and 2-h PG approximately 10.0 mmol/l; for adults, this increase occurred at FPG approximately 7.5 mmol/l and 2-h PG approximately 10.3 mmol/l. Sensitivity of the adult diagnostic guidelines of FPG > or =7.0 mmol/l and 2-h PG > or =11.1 mmol/l for the detection of microvascular disease was much lower (with higher specificity) in youths than in adults. Receiver operating characteristics (ROC) curve areas were lower for FPG and 2-h PG for youths, suggesting that microvascular disease was less strongly predicted by baseline glucose. CONCLUSION--The current adult guidelines for diagnosis of diabetes are applicable to youth, as they identify a population at high risk of microvascular complications.     

A1C Cut Points to Define Various Glucose Intolerance Groups in Asian Indians

OBJECTIVE

To determine A1C cut points for glucose intolerance in Asian Indians.

RESEARCH DESIGN AND METHODS

A total of 2,188 participants without known diabetes were randomly selected from the Chennai Urban Rural Epidemiology Study. All had fasting plasma glucose (FPG) and 2-h postload plasma glucose measurements after a 75-g load and were classified as having impaired fasting glucose (IFG) (American Diabetes Association [ADA] criteria, FPG ≥5.5 and <7 mmol/l, and World Health Organization [WHO] criteria, FPG ≥6.1 and <7 mmol/l), impaired glucose tolerance (IGT) (2-h postload plasma glucose ≥7.8 and <11.1 mmol/l), or diabetes (FPG ≥7 mmol/l and/or 2-h postload plasma glucose ≥11.1 mmol/l). A1C was measured using the Bio-Rad Variant machine. Based on receiver operating characteristic curves, optimum sensitivity and specificity were derived for defining A1C cut points for diabetes, IGT, and IFG.

RESULTS

Mean ± SD values of A1C among subjects with normal glucose tolerance, IGT, and diabetes were 5.5 ± 0.4, 5.9 ± 0.6, and 8.3 ± 2.0%, respectively (P_trend < 0.001) with considerable overlap. To identify diabetes based on 2-h postload plasma glucose, the A1C cut point of 6.1% had an area under the curve (AUC) of 0.941 with 88.0% sensitivity and 87.9% specificity. When diabetes was defined as FPG ≥7.0 mmol/l, the A1C cut point was 6.4% (AUC = 0.966, sensitivity 93.3%, and specificity 92.3%). For IGT, AUC = 0.708; for IFG, AUC = 0.632 (WHO criteria) and 0.708 (ADA criteria), and the A1C cut point was 5.6%.

CONCLUSIONS

In Asian Indians, A1C cut points of 6.1 and 6.4% defined diabetes by 2-h postload plasma glucose or FPG criteria, respectively. A value of 5.6% optimally identified IGT or IFG but was <70% accurate.A1C is an indicator of the average blood glucose concentrations over the preceding 2–3 months and is currently considered the best index of metabolic control in individuals with diabetes (1). The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study (UKPDS) have demonstrated that lowering A1C can reduce the risk of diabetes microvascular complications (2,3). An association between A1C and cardiovascular risk factors in subjects with normal glucose tolerance (NGT) was also reported (4).Until recently, A1C had not been recommended as a diagnostic or a screening tool because of several factors: lack of standardization, low sensitivity, and high cost (5). However, after efforts to improve standardization of the A1C assay and the introduction of the new International Federation of Clinical Chemists (IFCC) standards, A1C is now being considered for diagnostic and screening purposes (6). A1C does not need to be measured in a fasting state or with a glucose load and, therefore, offers potential ease and convenience. A recent American Diabetes Association (ADA) International Expert Committee proposed an A1C cut point of 6.5% as a diagnostic test for diabetes (7). It is important to investigate whether these cut points for A1C apply to all populations worldwide. The normative distribution for A1C levels has been described in western populations in subjects with NGT as well as those with impaired glucose tolerance (IGT) (8). However, there are no reports of the normative A1C distributions, to our knowledge, from India, which currently has the largest number of individuals with diabetes in the world. Here, we examine the distribution of A1C in a south Indian population and explore optimal cut points for identifying diabetes and high-risk pre-diabetic groups.     

Estimated number of adults with prediabetes in the US in 2000: opportunities for prevention

OBJECTIVE: To estimate the percent and number of overweight adults in the U.S. with prediabetes who would be potential candidates for diabetes prevention as per the American Diabetes Association Position Statement (12). RESEARCH DESIGN AND METHODS: We analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III; 1988-1994) and projected our estimates to the year 2000. We defined impaired glucose tolerance (IGT; 2-h glucose 140-199 mg/dl), impaired fasting glucose (IFG; fasting glucose 110-125 mg/dl), and prediabetes (IGT or IFG) per American Diabetes Association (ADA) criteria. The ADA recently recommended that all overweight people (BMI >or=25 kg/m(2)) who are >or=45 years of age with prediabetes could be potential candidates for diabetes prevention, as could prediabetic people aged >25 years with risk factors. In NHANES III, 2-h postload glucose concentrations were done only among subjects aged 40-74 years. Because we were interested in overweight people who had both the 2-h glucose and fasting glucose tests, we limited our estimates of IGT, IFG, and prediabetes to those aged 45-74 years. RESULTS-Overall, 17.1% of overweight adults aged 45-74 years had IGT, 11.9% had IFG, 22.6% had prediabetes, and 5.6% had both IGT and IFG. Based on those data, we estimated that in the year 2000, 9.1 million overweight adults aged 45-74 had IGT, 5.8 million had IFG, 11.9 million had prediabetes, and 3.0 million had IGT and IFG. CONCLUSIONS: Almost 12 million overweight individuals aged 45-74 years in the U.S. may benefit from diabetes prevention interventions. The number will be substantially higher if estimation is extended to individuals aged >75 and 25-44 years.     

From policemen to policies: what is the future for 2-h glucose? The Kelly West Lecture, 2000.

OBJECTIVE: To describe the characteristics and vital prognosis of men with diabetes diagnosed by one fasting plasma glucose (FPG) concentration > or =7.0 mmol/l, with diabetes diagnosed by one isolated postchallenge hyperglycemia (IPH) (FPG <7.0 mmol/l and a 2-h plasma glucose concentration > or =11.1 mmol/l), or with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: This study involved a cohort of 6,881 Caucasian nondiabetic men from the Paris Prospective Study, aged 44-55 years, who were followed for cause of death for 20 years. RESULTS: Diabetes was diagnosed in 4.3% of the men (1.0% diabetes diagnosed by IPH), and IGT was diagnosed in 9% of the men. At baseline, the men with diabetes diagnosed by IPH had a lower cardiovascular risk profile than those with diabetes diagnosed by FPG, as did the men with IGT and a normal fasting glucose level (<6.1 mmol/l, IGT and normal fasting glucose), compared with men with impaired fasting glucose (6.1-6.9 mmol/l, IGT and impaired fasting glucose [IFG]). At 20 years of follow-up, all-cause and cancer death rates were higher in men with diabetes diagnosed by IPH than in men with diabetes diagnosed by FPG (55 vs. 44%, P < 0.1 and 31 vs. 17%, P < 0.01, respectively) but were not significantly different for coronary causes (6 vs. 11%). Men with IGT and normal fasting glucose also had significantly higher cancer death rates than men with IGT and IFG. CONCLUSIONS: The most likely explanation for the high cancer and low coronary death rates is that men with diabetes diagnosed by IPH consumed alcohol; the men in this study drank 49 g of pure alcohol on average per day, equivalent to 0.6 l of wine. If these results are confirmed by other prospective studies, screening subjects for isolated postchallenge hyperglycemia may not be worthwhile.     

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.     

Factors responsible for development from normal glucose tolerance to isolated postchallenge hyperglycemia

OBJECTIVE: Isolated postchallenge hyperglycemia (IPH), defined as fasting plasma glucose (FPG) level <7.0 mmol/l and 2-h plasma glucose (PG) level >/=11.1 mmol/l, is a subtype of early-stage diabetes. This study evaluates the metabolic profiles of insulin secretion and insulin sensitivity in IPH to clarify the factors responsible for development of this form of type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted cross-sectional analysis of 231 Japanese men aged 20-70 years. The subjects were classified into the following three groups, based on the results of a 75-g oral glucose tolerance test (OGTT): 1) normal glucose tolerance (NGT), defined as FPG level <6.1 mmol/l and 2-h PG level <7.8 mmol/l (n = 89); 2) impaired glucose tolerance (IGT), defined as FPG level <7.0 mmol/l and 2-h PG level of 7.8-11.1 mmol/l (n = 94); and 3) IPH (n = 48). We compared the three groups for insulin secretion (insulinogenic index) and insulin sensitivity (index of insulin resistance using homeostasis model assessment [HOMA-IR]). RESULTS: The insulinogenic index in IPH was the lowest of the three groups (P < 0.001 versus NGT). The HOMA-IR in the IGT and IPH groups were significantly higher than in the NGT group (P < 0.001), but both were similar. By linear regression analysis, the insulinogenic index rather than fasting insulin or HOMA-IR was the more significant factor in the 2-h PG level in IGT and IPH. CONCLUSIONS: Subjects with IPH exhibited distinctly impaired early-phase insulin secretion and only mild insulin resistance, indicating that reduced insulin secretion is the primary determinant of deterioration from NGT to IGT and IPH in development of type 2 diabetes in these subjects.     

Combined use of fasting plasma glucose and HbA1c predicts the progression to diabetes in Chinese subjects

OBJECTIVE: We have previously suggested using the paired values of fasting plasma glucose (FPG) and HbA1c to identify potential diabetic subjects. In this article, we followed up on 208 nondiabetic subjects and examined their rates of progression to diabetes. We analyzed their likelihood of becoming diabetic according to their baseline FPG and HbA1c concentrations. RESEARCH DESIGN AND METHODS: Between 1988 and 1995, 2,877 Chinese subjects with risk factors for diabetes underwent screening. Of these, 2,250 had FPG <7.8 mmol/l and 2-h plasma glucose (PG) <11.1 mmol/l. Of these 2,250 subjects, 265 were randomly recruited for an annual oral glucose tolerance test (OGTT) until they progressed to develop diabetes. Of those 265 subjects, 57 had baseline FPG > or =7.0 mmol/l and were excluded from the present analysis. Hence, the progression of glucose tolerance in 208 subjects who were nondiabetic according to the new American Diabetes Association diagnostic criteria (FPG < 7.0 mmol/l and 2-h PG < 11.1 mmol/l) was examined RESULTS: Of the 208 nondiabetic subjects, 26 (12.5%) were men and 182 (87.5%) were women. After a mean follow-up of 1.60 +/- 1.16 years (range 1-7, median 1), 44 (21.2%) progressed to develop diabetes and 164 (78.8%) remained nondiabetic. Those who were diabetic at the end of the study had a high likelihood ratio (LR) of 9.3 to have baseline FPG > or =6.1 mmol/l and baseline HbA1c > or =6.1%. This was compared with a low LR of 0.6-1.1 in diabetic subjects who had either FPG <6.1 mmol/l or HbA1c <6.1% or both at baseline. The crude rate of progression to diabetes was more than five times higher (44.1 vs. 8.1%) in those whose baseline FPG was > or =6.1 mmol/l and baseline HbA1c was > or =6.1% compared with those whose baseline FPG was <6.1 mmol/l and baseline HbA1c was <6.1%. CONCLUSIONS: For Chinese subjects with risk factors for glucose intolerance, the use of paired FPG and HbA1c values helped to identify potential diabetic subjects. Those with an FPG > or =6.1 mmol/l and HbA1c > or =6.1% had a rate of progression to diabetes more than five times higher than those with an FPG <6.1 mmol/l and an HbA1c <6.1% after a mean follow-up of 1.6 years. Those with an FPG > or =6.1 but <7.0 mmol/l, especially if their HbA1c was > or =6.1%, should undergo an OGTT to confirm diabetes. Subjects with an FPG <6.1 mmol/l and/or an HbA1c <6.1% should have regular screening using the paired values of FPG and HbA1c.     

冠心病患者血糖水平与冠状动脉病变Gensini评分的相关性研究

目的探讨冠心病患者血糖水平与冠状动脉病变Gensini评分的相关性。方法入选经冠状动脉造影确诊冠心病,并排除糖尿病的患者328例,行口服葡萄糖耐量（OGTT）试验,根据OGTT试验结果,将患者分为5组,血糖正常组、单纯空腹血糖受损（IFG）组、单纯糖耐量受损（IGT）组、复合糖耐量受损组、新诊断糖尿病组,通过Gensini评分系统对其冠状动脉病变程度进行评分,进行组间冠心病危险因素和冠状动脉病变程度比较,同时对FPG、2hPG水平与冠状动脉病变Gemini进行单因素和多因素分析。结果单纯空腹血糖受损组、单纯糖耐量受损组、复合糖耐量受损组及新诊断糖尿病组的冠状动脉病变总积分均高于血糖正常组（P均〈0．05）;尤以IGT组、复合糖耐量受损组、新诊断糖尿病组增高显著;空腹血糖受损、糖耐量受损、复合糖耐量受损组、新诊断糖尿病组的组间冠状动脉病变总积分无显著差异（P均〉0．05）。2hPG与冠状动脉病变Gensini积分（r=0．358;P〈0．001）呈正相关,FPG与冠状动脉病变Gemini积分（r=0．232;P=0．046）呈正相关。多元逐步回归分析显示2hPG与冠状动脉病变总积分（β=0．358,P=0．000）独立相关。结论IGT、IFG、新发糖尿病与冠状动脉粥样硬化密切相关,加重冠状动脉病变程度,尤其以餐后血糖升高对冠状动脉病变的影响显著。     

空腹血糖及糖化血红蛋白用于筛查糖耐量减退的比较性研究

目的比较空腹血糖（FPG）和糖化血红蛋白（HbAlc）在筛查糖耐量减退（IGT）中的应用价值。方法到我院门诊为明确有无血糖异常而就诊者336人，测定空腹血糖、糖化血红蛋白，并行口服葡萄糖耐量试验（OGTT）。结果按照1999年WHO的DM诊断标准，本研究人群空腹血糖〈6．1者124例，≥6．1-〈7．0者56例，≥7．0者156例；糖化血红蛋白〈6．1者84例，≥6．1者252例；OGTT2 hPG〈7．8者92例，≥7．8-〈11．1者99例，≥11．1者145例。结论糖化血红蛋白和空腹血糖均不适用于筛查IGT人群，但糖化血红蛋白比空腹血糖提示病人是否存在血糖异常更敏感。     

Outline of revision of classification and diagnostic criteria of diabetes mellitus in Japan

Japan Diabetes Society organized a committee for the revision of diagnostic criteria of diabetes mellitus in 1995. Like ADA and WHO reports, this committee adopts a classification based on etiologies, and presents a two-dimensional figure with etiologies and the state of insulin deficiency on different axis. The words IDDM and NIDDM will be retained as terms representing the different degree of insulin deficiency. On the basis of glycemia, diabetic type is defined when fasting plasma glucose exceeded 126 mg/dl and/or 2-hour plasma glucose by 75 g GTT exceeded 200 mg/dl. The diagnosis of diabetes in an individual can be made by confirming sustained diabetic type on repeated tests or co-existance of characteristic clinical features of diabetes. Normal type is defined by FPG < 110 mg/dl and 2hPG < 140 mg/dl. The borderline type, defined as neither normal nor diabetic types, corresponds to IFG plus IGT according to ADA and WHO reports. The application of HbA1c for diagnosis of diabetes and the criteria for gestational diabetes mellitus are also discussed.     

Using HbA(1c) to improve efficacy of the american diabetes association fasting plasma glucose criterion in screening for new type 2 diabetes in American Indians: the strong heart study

OBJECTIVE: To find an optimal critical line in the fasting plasma glucose (FPG)-HbA(1c) plane for identifying diabetes in participants with impaired fasting glucose (IFG) and thereby improve the efficacy of using FPG alone in diabetes screening among American Indians. RESEARCH DESIGN AND METHODS: We used FPG, 2-h postload glucose (2hPG), and HbA(1c) measured in the 2,389 American Indians (aged 45-74 years, without diabetes treatment or prior history of diabetes) in the Strong Heart Study (SHS) baseline (second) examination. Participants were classified as having diabetes if they had either FPG > or =126 mg/dl or 2hPG > or =200 mg/dl, as having IFG if they had 110 < or = FPG < 126 mg/dl, and as having normal fasting glucose (NFG) if they had FPG <110, according to the American Diabetes Association (ADA) definition. Logistic regression models were used for identifying diabetes (2hPG > or =200 mg/dl) in IFG participants. The areas under the receiver operating characteristic (ROC) curves generated by different logistic regression models were evaluated and compared to select the best model. A utility function based on the best model and the cost-to-benefit ratio was used to find the optimal critical line. The data from the second examination were used to study the effect of the time interval between the successive diabetes screenings on both the FPG criterion and the optimal critical line. RESULTS: A total of 37% of all subjects with new diabetes at baseline and 55.2% of those in the second exam had 2hPG > or =200 but FPG <126. There was a very large portion of IFG participants with diabetes (19.3 and 22.9% in the baseline and second exam, respectively). Among the areas under the ROC curves, the area generated by the logistic regression model on FPG plus HbA(1c) is the largest and is significantly larger than that based on FPG (P = 0.0008). For a cost-to-benefit ratio of 0.23888, the optimal critical line that has the highest utility is: 0.89 x HbA(1c) + 0.11 x FPG = 17.92. Those IFG participants whose FPG and HbA(1c) were above or on the line were referred to take an oral glucose tolerance test (OGTT) to diagnose diabetes. The optimal critical line is lower if a successive diabetes screening will be conducted 4 years after the previous screening. CONCLUSIONS: FPG > or =126 and 2hPG > or =200, as suggested by the ADA, are used independently to define diabetes. The FPG level is easy to obtain, and using FPG alone is suggested for diabetes screening. It is difficult to get physicians and patients to perform an OGTT to get a 2hPG level because of the many drawbacks of the OGTT, especially in those patients who already have FPG <126. It is also impractical to conduct an OGTT for everyone in a diabetes screening. Our data show that 37% of all subjects with new diabetes in the SHS baseline exam and 55.2% of those in the second exam have 2hPG > or =200 but FPG <126. These cases of diabetes cannot be detected if FPG is used alone in a diabetes screening. Therefore, although the small portion of diabetes in the NFG group (4.7% in the baseline and 6.9% in the second exam) may be ignored, those cases of diabetes among IFG participants ( approximately 20% in our data) need further consideration in a diabetes screening. It may be worthwhile for those IFG participants identified by the optimal critical line to take an OGTT. The optimal critical line and time interval between successive diabetes screenings need further study.     

Cardiovascular risk profile in individuals with borderline glycemia: the effect of the 1997 American Diabetes Association diagnostic criteria and the 1998 World Health Organization Provisional Report

OBJECTIVE: In 1997, the American Diabetes Association (ADA) recommended a new diagnostic category, impaired fasting glucose (IFG), to describe individuals with borderline glucose tolerance. On the other hand, the World Health Organization (WHO) suggested retaining the category of impaired glucose tolerance (IGT). We studied the prevalence of IFG and IGT in a multiethnic society and compared the cardiovascular risk profiles of subjects with IFG, IGT, or both IFG and IGT. RESEARCH DESIGN AND METHODS: A total of 3,568 subjects were examined from the 1992 National Health Survey of Singapore, which involved a combination of disproportionately stratified sampling and systematic sampling. Anthropometric, blood pressure, insulin, lipid profile, and uric acid measurements were taken, and a standard 75-g oral glucose tolerance test was performed after a 10-h overnight fast. RESULTS: The prevalence rates of IFG only, IGT only, and both IFT and IGT were 3.45, 10.2, and 3.4%, respectively. The degree of agreement (kappa) between the two diagnostic criteria (the ADA IFG and the WHO IGT) was only 0.25. A fasting glucose level of 5.5 mmol/l was the optimal cutoff for predicting a 2-h postload glucose level of > or =7.8 mmol/l. The following cardiovascular risk factors were higher in subjects with both IFG and IGT compared with those with either IFG or IGT alone: systolic blood pressure (131 +/- 20 vs. 125 +/- 21 and 125 +/- 19 mmHg, respectively; P < 0.05 and P < 0.001, respectively); diastolic blood pressure (77 +/- 12 vs. 73 +/- 12 and 74 +/- 12 mmHg, respectively; P < 0.05); BMI (26.2 +/- 4.2 vs. 24.4 +/- 4.0 and 24.6 +/- 4.4 kg/m2, respectively; P < 0.01 and P < 0.001, respectively); waist circumference (84.1 +/- 10.3 vs. 79.3 +/- 10.7 and 79.3 +/- 10.6 cm, respectively; P < 0.001); waist-to-hip ratio (0.84 +/- 0.08 vs. 0.82 +/- 0.09 and 0.81 +/- 0.08, respectively; P < 0.05 and P < 0.001, respectively); fasting insulin (12.1 +/- 9.7 vs. 9.2 +/- 5.3 and 9.9 +/- 7.7 mU/l; P < 0.01); insulin resistance (by homeostasis model assessment [HOMA]) (3.41 +/- 2.77 vs. 2.58 +/- 1.50 and 2.43 +/- 1.83, respectively; P < 0.01 and P < 0.001, respectively); total cholesterol (5.81 +/- 1.1 vs. 5.51 +/- 1.1 and 5.53 +/- 1.1 mmol/l, respectively; P < 0.05) and apolipoprotein(B) [apo(B)] (1.5 +/- 0.38 vs. 1.40 +/- 0.34 and 1.39 +/- 0.35 mmol/l, respectively; P < 0.01). The pattern of difference remained significant only for fasting insulin, insulin resistance (HOMA), and apo(B) (borderline) after adjustment for age, sex, and ethnic differences. CONCLUSIONS: Obvious discordance was evident in the classification of glycemic status when applying the criteria proposed by the ADA (IFG) or WHO (IGT) in a multiethnic society like Singapore. However, subjects with either IFG or IGT had similar cardiovascular risk profiles. Therefore, both criteria identified individuals at high risk for cardiovascular disease. Individuals with both IFG and IGT had a greater incidence of the cardiovascular dysmetabolic syndrome.     

Glycemic thresholds for diabetes-specific retinopathy: implications for diagnostic criteria for diabetes

OBJECTIVE

To re-evaluate the relationship between glycemia and diabetic retinopathy.

RESEARCH DESIGN AND METHODS

We conducted a data-pooling analysis of nine studies from five countries with 44,623 participants aged 20–79 years with gradable retinal photographs. The relationship between diabetes-specific retinopathy (defined as moderate or more severe retinopathy) and three glycemic measures (fasting plasma glucose [FPG; n = 41,411], 2-h post oral glucose load plasma glucose [2-h PG; n = 21,334], and A1C [n = 28,010]) was examined.

RESULTS

When diabetes-specific retinopathy was plotted against continuous glycemic measures, a curvilinear relationship was observed for FPG and A1C. Diabetes-specific retinopathy prevalence was low for FPG <6.0 mmol/l and A1C <6.0% but increased above these levels. Based on vigintile (20 groups with equal numbers) distributions, glycemic thresholds for diabetes-specific retinopathy were observed over the range of 6.4–6.8 mmol/l for FPG, 9.8–10.6 mmol/l for 2-h PG, and 6.3–6.7% for A1C. Thresholds for diabetes-specific retinopathy from receiver-operating characteristic curve analyses were 6.6 mmol/l for FPG, 13.0 mmol/l for 2-h PG, and 6.4% for A1C.

CONCLUSIONS

This study broadens the evidence based on diabetes diagnostic criteria. A narrow threshold range for diabetes-specific retinopathy was identified for FPG and A1C but not for 2-h PG. The combined analyses suggest that the current diabetes diagnostic level for FPG could be lowered to 6.5 mmol/l and that an A1C of 6.5% is a suitable alternative diagnostic criterion.The current diagnostic cut points for diabetes (fasting plasma glucose [FPG] of 7.0 mmol/l and 2-h post oral glucose load plasma glucose [2-h PG] of 11.1 mmol/l) are largely based on glycemic levels associated with a substantially increased risk of diabetes-associated microvascular complications, particularly retinopathy, above these levels (1,2). These cut points were derived from cross-sectional epidemiological studies that examined retinopathy across a range of glycemic levels. The datasets used for this purpose were from Pima Indians, an Egyptian study, and unpublished data from the Third National Health and Nutrition Examination Survey (NHANES) (2).Other studies (3–5) also have examined this relationship, but the results have been inconsistent. All studies reported to date have had limited statistical power to examine this relationship in detail and have adopted a very broad definition of retinopathy that included many cases of mild retinopathy, now known to have causes other than hyperglycemia (6). A more clinically relevant end point is diabetes-specific retinopathy (moderate or more severe levels of retinopathy) that is invariably attributed to hyperglycemia. Also different statistical methods have been used in previous studies, which has an important effect on derived cut points (5,7).Several new datasets with retinopathy data have become available since the original studies used to derive current diabetes diagnostic cut points (1,2). The DETECT-2 collaboration has pooled these datasets to examine and re-evaluate the relationship between retinopathy and three glycemic measures: FPG, 2-h PG, and A1C. The size of the DETECT-2 dataset has allowed us to focus on the relationship between measures of glycemia and diabetes-specific retinopathy (i.e., moderate or more severe levels of retinopathy). These analyses were designed to inform current deliberations on possible revisions to the diagnostic criteria for diabetes.     

Impaired fasting glucose in cystic fibrosis

OBJECTIVE

While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fasting glucose (IFG) has scarcely been explored. No studies have examined the relation between IFG and clinical status.

RESEARCH DESIGN AND METHODS

Data were retrieved from the University of Minnesota CF database on oral glucose tolerance tests (OGTTs) performed in 1996–2005. Subjects were identified as normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CF–related diabetes without fasting hyperglycemia (CFRD FH−). Patients with fasting hyperglycemia were excluded. The presence of IFG was assessed within each category. In a separate case-control cohort study, subjects with IFG were matched to CF control subjects by age, sex, and OGTT class to explore outcomes.

RESULTS

For the total population (n = 310), the prevalence of IFG was 22%, and by OGTT class was NGT 14%, IGT 31%, CFRD FH− 53%. Within the cohort study, mortality was significantly reduced in IFG (two vs. nine deaths, odds ratio [OR] = 0.2 [95% CI 0.04–0.9]). IFG did not confer increased risk of progression to diabetes (OR 0.66 [0.29–1.48]). Lung function was better in pediatric IFG subjects with IGT and not significantly worse in adults with IGT or adults and children with NGT and CFRD FH−. BMI was not significantly different in IFG subjects versus control subjects.

CONCLUSIONS

Contrary to expectations in patients with CF, IFG appeared to be associated with improved survival and was not associated with worse nutritional or pulmonary status or increased progression to fasting hyperglycemia.Oral glucose tolerance test (OGTT) categories were defined decades ago by the World Health Organization (WHO). In 1997, the American Diabetes Association (ADA) lowered the fasting glucose level used to define diabetes from 140 mg/dl (7.8 mmol/l) to 126 mg/dl (7.0 mmol/l) to better reflect risk of microvascular complications. The ADA also introduced the concept of impaired fasting glucose (IFG) because fasting glucose elevation in the range of 110–125 mg/dl (6.1–6.9 mmol/l) was shown to be a risk factor for the development of diabetes. In 2003, the ADA further lowered this prediabetes threshold to 100 mg/dl (5.6), again based on the future risk of developing diabetes. Using these newer criteria, the prevalence of IFG in the general population may be as high as 30% among U.S. adults (1) and 11% among adolescents (2).Oral glucose tolerance abnormalities are found in the majority of patients with cystic fibrosis (CF) (3), but IFG has been infrequently reported (4,5). No studies have reported current or future clinical outcomes in CF patients with IFG. Because impaired glucose tolerance (IGT) is associated with pulmonary function deterioration in CF (6) and risk of progression to diabetes (7), we hypothesized that IFG would also be associated with worse clinical status and the development of diabetes. Our aim was to determine the prevalence of IFG in the University of Minnesota (UM) CF population and the consequences of that diagnosis over a period of at least 3.5 years'' follow-up.     

A1C Between 5.7 and 6.4% as a Marker for Identifying Pre-Diabetes, Insulin Sensitivity and Secretion, and Cardiovascular Risk Factors: The Insulin Resistance Atherosclerosis Study (IRAS)

OBJECTIVE

A1C is an optional method for diagnosing diabetes and also for detecting individuals at increased risk of the disease. However, how A1C compares with fasting (FPG) and 2-h plasma glucose for detecting at-risk individuals is not well known.

RESEARCH DESIGN AND METHODS

A 2-h glucose tolerance test, frequently sampled intravenous glucose tolerance test, and A1C were obtained at the follow-up examination in 855 participants in the Insulin Resistance Atherosclerosis Study (IRAS). For this report, 385 individuals were at increased risk of diabetes as defined by A1C between 5.7 and 6.4%, impaired glucose tolerance (IGT), and/or impaired fasting glucose (IFG).

RESULTS

IFG and IGT identified 69.1 and 59.5% of all individuals at increased risk of diabetes, respectively. A1C 5.7–6.4% detected 23.6% of all at-risk individuals, although more African Americans (31.4%) and Hispanics (35.2%) than non-Hispanic whites (9.9%). Relative to A1C, FPG was more strongly related to fasting insulin (r = 0.38 vs. 0.26; P < 0.01), acute insulin response (r = – 0.20 vs. – 0.09; P < 0.01), and waist circumference (r = 0.43 vs. 0.25; P < 0.001) by the Spearman correlation test. Similarly, 2-h plasma glucose was more strongly related to Si (r = – 0.40 vs. – 0.27; P < 0.01) and triglycerides (r = 0.30 vs. 0.08; P < 0.001).

CONCLUSIONS

A1C 5.7–6.4% is less sensitive for detecting at-risk individuals than IFG and IGT, particularly among non-Hispanic whites. Single determinations of FPG and 2-h plasma glucose seem to be more precise correlates of insulin resistance and secretion than A1C and, in general, better for other metabolic disorders.A1C has been proposed by the American Diabetes Association (ADA) as an optional assay for diagnosing diabetes and also for detecting individuals at increased risk of the disease (1). A1C has been shown to predict future onset of diabetes (2–4) and is better than fasting plasma glucose (FPG) for predicting microvascular complications (1). A1C may be superior to FPG in predicting mortality and cardiovascular risk in nondiabetic individuals (5) but inferior to 2-h glucose concentration (2-h plasma glucose) in most studies (6–8), albeit not all (9). The A1C assay has advantages over the measurement of plasma glucose including convenience (not requiring fasting samples) and superior technical attributes (1). Conversely, the number of individuals diagnosed with diabetes by the 6.5% A1C threshold is significantly smaller than the number of those diagnosed by the 2003 American Diabetes Association (ADA) criteria (10–13). A1C, FPG, and 2-h plasma glucose assess different aspects of glucose metabolism (1), but differences in the relation of these three glycemic measures to insulin resistance, insulin secretion, and other metabolic abnormalities have not been described.A1C between 5.7 and 6.4% (A1C 5.7–6.4%) is now considered a category of increased risk for diabetes in addition to impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) (1). However, studies that compare A1C 5.7–6.4% with IFG and IGT are lacking. Therefore, our aim was twofold: 1) to analyze A1C, FPG, and 2-h plasma glucose for their ability to identify individuals at increased risk of diabetes; and 2) to examine the relation of these glycemic measures to other metabolic abnormalities, particularly measured insulin resistance and secretion in nondiabetic subjects.     

The American Diabetes Association and World Health Organization classifications for diabetes: their impact on diabetes prevalence and total and cardiovascular disease mortality in elderly Japanese-American men

OBJECTIVE: To compare the prevalence of diabetes according to the American Diabetes Association (ADA) and World Health Organization (WHO) classifications in a sample of elderly Japanese-American men; to examine the association with total and cardiovascular mortality by diabetes status using both classifications; and to determine whether the fasting or 2-h glucose measurement is a stronger predictor of adverse outcomes. RESEARCH DESIGN AND METHODS: Examinations given from 1991 to 1993 in the Honolulu Heart Program were used as baseline for these analyses. Subjects were 71-93 years of age at that time and were followed for total and cardiovascular disease mortality for up to 7 years. RESULTS: A total of approximately 66% of individuals who had diabetes by WHO criteria were missed when the ADA definition was used. The relative risks of total and cardiovascular mortality for those with versus those without diabetes were similar for both definitions; however, when fasting and postload glucose measures were analyzed as continuous variables, the 2-h measurement was a superior predictor and was independent of fasting glucose. In contrast, fasting glucose was not an independent predictor of these outcomes in the presence of the 2-h measurement. CONCLUSIONS: The prevalence of glucose metabolism abnormalities was very high among elderly Japanese-American men. The WHO classification was superior to the ADA classification in identification of subjects at high risk for adverse outcomes. Therefore, we conclude that the 2-h glucose measurement is valuable and should be retained in epidemiologic studies.     

Assessment of glucose tolerance test criteria for diagnosis of diabetes in Chinese subjects.

OBJECTIVE--To examine and compare WHO diagnostic criteria for diabetes mellitus. RESEARCH DESIGN AND METHOD--The relationship between FPG and 2-h glucose are examined in 680 OGTTs with a quadratic regression model and ROC analysis. Simultaneous measurements of HbA1 and fructosamine are also compared with multiple linear regression. RESULTS--Two hundred eighteen subjects (32%) had 2-h glucose greater than or equal to 11.1 mM, of which only 86 had FPG greater than or equal to 7.8 mM. Only 2 subjects had FPG greater than 7.8 mM and 2-h glucose less than 7.8 mM. Of subjects with 2-h glucose less than 7.8 mM (n = 332), only 9 had FPG greater than 6.0 mM. From the quadratic model, the predicted FPG corresponding to 2-h glucose = 11.1 mM was 5.7 mM, whereas the predicted 2-h glucose corresponding to FPG = 7.8 mM was 15.2 mM. ROC analysis showed that, with 2-h glucose greater than or equal to 11.1 mM as indicating diabetes, an FPG of 5.6 mM gave an intersect for sensitivity and specificity of 87%. HbA1 and fructosamine correlated more closely with 2-h glucose and area under the OGTT curve than with FPG. CONCLUSIONS--Given that a 2-h glucose cutoff of 11.1 mM can be justified from other studies, our results suggest that the FPG cutoff of 7.8 mM when used for screening purposes should be reduced. At a suggested value of 7.0 mM, specificity remains 98.5%, whereas sensitivity increases to 57%.     

Impaired fasting glucose or impaired glucose tolerance. What best predicts future diabetes in Mauritius?

OBJECTIVE: To determine if impaired fasting glucose (IFG; fasting plasma glucose level 6.1-6.9 mmol/l) can predict future type 2 diabetes as accurately as does impaired glucose tolerance (IGT; 2-h plasma glucose level 7.8-11.0 mmol/l). RESEARCH DESIGN AND METHODS: A longitudinal population-based study was performed with surveys in 1987 and 1992 on the island of Mauritius, assessing diabetes status by the oral glucose tolerance test. A total of 3,717 subjects took part in both surveys. Of these subjects, 3,229 were not diabetic in 1987 and formed the basis of this study. RESULTS: At baseline, there were 607 subjects with IGT and 266 subjects with IFG. There were 297 subjects who developed diabetes by 1992. For predicting progression to type 2 diabetes, the sensitivity, specificity, and positive predictive values were 26, 94, and 29% for IFG and 50, 84, and 24% for IGT, respectively. Only 26% of subjects that progressed to type 2 diabetes were predicted by their IFG values, but a further 35% could be identified by also considering IGT. The sensitivities were 24% for IFG and 37% for IGT in men and 26% for IFG and 66% for IGT in women, respectively. CONCLUSIONS: These data demonstrate the higher sensitivity of IGT over IFG for predicting progression to type 2 diabetes. Screening by the criteria for IFG alone would identify fewer people who subsequently progress to type 2 diabetes than would the oral glucose tolerance test.     

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.