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.     

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.     

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.     

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。     

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.     

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.     

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.     

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.     

Screening for type 2 diabetes and impaired glucose metabolism: the Australian experience

OBJECTIVE: To assess the Australian protocol for identifying undiagnosed type 2 diabetes and impaired glucose metabolism. RESEARCH DESIGN AND METHODS: The Australian screening protocol recommends a stepped approach to detecting undiagnosed type 2 diabetes based on assessment of risk status, measurement of fasting plasma glucose (FPG) in individuals at risk, and further testing according to FPG. The performance of and variations to this protocol were assessed in a population-based sample of 10,508 Australians. RESULTS: The protocol had a sensitivity of 79.9%, specificity of 79.9%, and a positive predictive value (PPV) of 13.7% for detecting undiagnosed type 2 diabetes and sensitivity of 51.9% and specificity of 86.7% for detecting impaired glucose tolerance (IGT) or impaired fasting glucose (IFG). To achieve these diagnostic rates, 20.7% of the Australian adult population would require an oral glucose tolerance test (OGTT). Increasing the FPG cut point to 6.1 mmol/l (110 mg/dl) or using HbA(1c) instead of FPG to determine the need for an OGTT in people with risk factors reduced sensitivity, increased specificity and PPV, and reduced the proportion requiring an OGTT. However, each of these protocol variations substantially reduced the detection of IGT or IFG. CONCLUSIONS: The Australian screening protocol identified one new case of diabetes for every 32 people screened, with 4 of 10 people screened requiring FPG measurement and 1 in 5 requiring an OGTT. In addition, 1 in 11 people screened had IGT or IFG. Including HbA(1c) measurement substantially reduced both the number requiring an OGTT and the detection of IGT or IFG.     

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.     

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.     

Risk of diabetes in the new diagnostic category of impaired fasting glucose: a prospective analysis.

OBJECTIVE: To prospectively evaluate progression to diabetes in individuals with impaired glucose regulation as defined according to fasting glucose alone or an oral glucose tolerance test (OGTT) (i.e., both fasting and postload glucose) to compare the ability of these two screening methods to identify people at high risk of developing diabetes. RESEARCH DESIGN AND METHODS: A working population of 1,245 nondiabetic telephone company employees aged 40-59 years was studied by OGTT in 1980. Participants were classified according to baseline fasting glucose only (as encouraged by the American Diabetes Association [ADA]) or OGTT (as recommended by the 1998 World Health Organization [WHO] consultation). Progression to diabetes was evaluated 11.5 years later according to the 1997 ADA criteria of a fasting plasma glucose level > or =7.0 mmol/l. RESULTS: With the use of the OGTT, baseline prevalence of impaired glucose regulation was substantially higher than that with fasting glucose alone (7.2 vs. 3.2%); the two groups only overlap for 40.9% of the cases because a fairly large number of people with postload hyperglycemia (59.1%) have normal fasting glucose. Progression to diabetes in participants with normal fasting glucose and postload hyperglycemia is significantly more frequent than that of people with normoglycemia (32.5 vs. 7.2%; P < 0.001) and not significantly different from that of people with both fasting and postload hyperglycemia (i.e., 44.0%). However, the former are not identified as being at unusually high risk of diabetes unless an OGTT is performed. When the use of fasting glucose alone or OGTT was validated as a marker of progression to diabetes, sensitivity was substantially higher for the OGTT (33.3 vs. 9.0%) without major differences in specificity (92.6 vs. 97.0%). CONCLUSIONS: These data (the only data so far available in Caucasians) support the viewpoint that for the identification of people at high risk of diabetes, the use of the OGTT should be maintained.     

Lack of agreement between the revised criteria of impaired fasting glucose and impaired glucose tolerance in children with excess body weight

OBJECTIVE: The aim of this study was to describe the agreement between impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) in children with excess body weight using the original and the revised definitions of IFG. RESEARCH DESIGN AND METHODS: Obese and overweight children aged 4-17 years were included (n = 533). Anthropometric parameters and biochemical tests (fasting and 2-h glucose tests after an oral glucose load [1.75 g/kg]) were performed. Case subjects with a fasting plasma glucose >/=126 mg/dl were excluded. The diagnostic parameters of the original and the revised definitions of IFG for detecting IGT were estimated. The analysis of agreement between these categories was made using the kappa test. RESULTS: The prevalence of IFG increased from 6.2 to 13.3% using the new criteria. The prevalence of IFG became closer to the prevalence of IGT (14.8%). The revised criteria increased the sensitivity from 26.6 to 36.7%. However, the new IFG definition was not useful for identifying IGT cases. Of the 71 case subjects with IFG, only 29 (40.8%) had IGT. In addition, 50 case subjects with IGT (9.4%) and 13 with diabetes (2.4%) had a fasting glycemia <100 mg/dl. A poor agreement was found between the 2003 IFG definition and abnormal 2-h postchallenge plasma glucose (kappa = 0.359). The proportion of false-positive cases increased (36.3-59.1%) under the new definition. CONCLUSIONS: The new definition modestly increases the sensitivity of IFG for detecting IGT in children with excess body weight. Despite this, more than one-half of these cases are not detected. In addition, the false-positive rate was increased by 61%.     

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.     

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.     

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。     

Some comments on ADA and WHO reports on the new criteria for the diagnosis of diabetes mellitus

The Expert Committee of ADA and a WHO working group reported the new criteria for the diagnosis of diabetes mellitus in 1997 and 1998, respectively. However, similar conclusions were obtained in those separate reports. The main changes proposed are as follows. The diagnostic fasting plasma glucose value has been lowered to > or = 126 mg/dl. Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for the diabetes (plasma > or = 110 to < 126 mg/dl). It is hoped that the new criteria for the diagnosis will be useful in the therapeutic judgements of diabetes mellitus.     

Minimal Contribution of Fasting Hyperglycemia to the Incidence of Type 2 Diabetes in Subjects With Normal 2-h Plasma Glucose

OBJECTIVE

To assess the relative contribution of increased fasting and postload plasma glucose concentrations to the incidence of type 2 diabetes in subjects with a normal 2-h plasma glucose concentration.

RESEARCH DESIGN AND METHODS

A total of 3,450 subjects with 2-h plasma glucose concentration <140 mg/dl at baseline were followed up in the San Antonio Heart Study (SAHS) and the Botnia Study for 7–8 years. The incidence of type 2 diabetes at follow-up was related to the fasting, 1-h, and 2-h plasma glucose concentrations.

RESULTS

In subjects with 2-h plasma glucose <140 mg/dl, the incidence of type 2 diabetes increased with increasing fasting plasma glucose (FPG) and 1-h and 2-h plasma glucose concentrations. In a multivariate logistic analysis, after adjustment for all diabetes risk factors, the FPG concentration was a strong predictor of type 2 diabetes in both the SAHS and the Botnia Study (P < 0.0001). However, when the 1-h plasma glucose, but not 2-h plasma glucose, concentration was added to the model, FPG concentration was no longer a significant predictor of type 2 diabetes in both studies (NS). When subjects were matched for the level of 1-h plasma glucose concentration, the incidence of type 2 diabetes markedly increased with the increase in 1-h plasma glucose, but the increase in FPG was not associated with a significant increase in the incidence of type 2 diabetes.

CONCLUSIONS

An increase in postload glycemia in the normal range is associated with an increase in the incidence of type 2 diabetes. After controlling for 1-h plasma glucose concentration, the increase in FPG concentration is not associated with an increase in the incidence of type 2 diabetes.Impaired fasting glucose (IFG) was introduced in 1997 by the American Diabetes Association (ADA) (1), and, analogous with impaired glucose tolerance (IGT), it was meant to represent an intermediate stage in the transition from normal glucose tolerance (NGT) to overt type 2 diabetes. Both IFG and IGT indicate an increased risk for future type 2 diabetes (2–4). Previously (5–7), we have shown that the 1-h plasma glucose concentration has better predictive power than either fasting plasma glucose (FPG) or 2-h plasma glucose, suggesting that the 1-h plasma glucose concentration may have greater utility in identifying subjects at increased risk for type 2 diabetes in routine clinical practice.Previous studies have reported that IFG and IGT represent separate clinical entities, which are characterized by distinct metabolic abnormalities (8–13). Subjects with IGT manifest insulin resistance in skeletal muscle (9–12) and impaired β-cell function (both early and late phases of insulin secretion) (10,14–16), whereas subjects with IFG are characterized by increased hepatic insulin resistance (9,16), impaired early insulin response (12), and decreased non–insulin-dependent glucose clearance (15). Because of the prominent role of progressive β-cell failure in the development of hyperglycemia (17), the impairment in β-cell function in subjects with IGT represents a major pathogenic factor for their increased risk for future type 2 diabetes. Although the increase in fasting plasma glucose is associated with a decrease in first-phase insulin secretion (11–13,18), subjects with IFG have robust second-phase insulin secretion, and, when related to their prevailing level of insulin resistance, they have second-phase insulin secretion comparable with that of subjects with NGT (12,13). Thus, impaired β-cell function cannot fully explain the increased incidence of type 2 diabetes associated with the increase in FPG concentration, e.g., in subjects with isolated IFG.Previously we have shown a strong correlation between insulin resistance in skeletal muscle and liver (16). Thus, a strong correlation between FPG and postload plasma glucose concentrations is anticipated. Therefore, we hypothesized that the increased type 2 diabetes risk associated with the increase in FPG, at least in part, is due to the increased postprandial plasma glucose concentration associated with the increase in FPG and is not due to the increase in FPG per se. The aim of this study was to test this hypothesis.     

Is using WHO criteria for impaired fasting glycaemia appropriate as an indication for OGTT in patients at high risk of developing diabetes?

Aim: Impaired fasting glycaemia (IFG) is an indication for oral glucose tolerance test (OGTT). World health organisation and International Diabetes Federation define IFG as fasting plasma glucose (FPG) levels of 6.1–6.9 mmol/l. However, American Diabetes Association still recommends a range of 5.6–6.9 mmol/l as IFG. We performed an audit to assess the outcome of OGTT at various cut offs of FPG levels in patients at high risk of developing diabetes. Methods: Laboratory data on OGTT performed over a period of 1 year in a district general hospital were collected. Patients with FPG levels between 5.6 and 6.9 mmol/l were selected and the outcome was analysed. Results: Our audit shows that in patients with FPG levels of 5.6–6.0 mmol/l, 19% had diabetes and 43% had impaired glucose tolerance (IGT). Conclusion: The percentage of subjects with abnormal OGTT in our study is much higher than that of Decode study [Diabetologica, 42 (1999) 647] (7% diabetes and 29% IGT). However, Decode study had included general population whereas our data were collected from subjects who are at high risk of developing diabetes. We conclude that in these subjects the lower cut off level of 5.6 mmol/l for FPG should be used as an indication for OGTT.     

Changing the definition of impaired fasting glucose: impact on the classification of individuals and risk definition

OBJECTIVE: This study evaluates the impact of lowering the diagnostic threshold for impaired fasting glucose (IFG) from 6.1 to 5.6 mmol/l as proposed by the American Diabetes Association (ADA) on the prevalence of the condition, classification of individuals, and risk definition. RESEARCH DESIGN AND METHODS: A total of 1,285 employees of the Italian Telephone Company aged 35-59 years without known diabetes underwent an oral glucose tolerance test (OGTT). BMI, serum cholesterol, triglycerides, and blood pressure were measured. Medication use was recorded. RESULTS: With the new ADA criterion, the proportion of people diagnosed with IFG increased from 3.2 to 9.7%. The newly proposed IFG category identified 41% of all subjects with impaired glucose tolerance (IGT) compared with 16.2% identified with the use of the World Health Organization criterion for IFG; the improvement in accuracy has been achieved at the cost of classifying more previously "normal" subjects as having IFG (from 2.3 to 7.3%). Both IFG and IGT were associated with an unfavorable risk profile for diabetes and cardiovascular disease, with a higher estimated risk for IGT than IFG. CONCLUSIONS: Even with the revised diagnostic criterion, IFG and IGT identify distinct groups that have a different background risk. The cost/benefit of preventive measures tested in people with IGT may not apply to the new IFG category.