Modern diagnosis and classification of diabetes mellitus

In July 1997, the American Diabetes Association (ADA) has published new recommendations for the diagnosis and classification of diabetes mellitus. Except for gestational diabetes they should be identical to the new WHO recommendations (not yet published). From now on, only the fasting glucose should be used for clinical routine. The oral glucose tolerance test is no longer recommended for this purpose. The diagnostic cut-off level for fasting glucose was decreased from 140 mg/100 ml (venous plasma) to 126 mg/dl, and the range between 110 and 125 mg/100 ml was defined as impaired fasting glucose (IFG), a new diagnostic category introduced in analogy to impaired glucose tolerance (IGT). The lower diagnostic cut-off level for fasting glucose has been proposed because the risk of developing diabetic late complications (predominantly at the vascular system) is already increased in blood glucose ranges thought to be normal. The diagnostic criteria for gestational diabetes are unchanged and still discrepant between ADA and WHO. The two major forms of diabetes should be designated only as type 1- and type 2-diabetes with respect to etiology and pathogenesis. Type 1-diabetes was subdivided into an immune-mediated and into an idiopathic form. MODY (maturity-onset type diabetes in young people) was listed separately from type 2-diabetes under the category of genetic defects of beta-cell function, also mitochondrial diabetes (maternally inherited diabetes and deafness). Malnutrition-related diabetes has been omitted as a major form of diabetes.     

The 1997 American Diabetes Association criteria versus the 1985 World Health Organization criteria for the diagnosis of abnormal glucose tolerance: poor agreement in the Hoorn Study

OBJECTIVE: Recently, the American Diabetes Association (ADA) introduced new diagnostic criteria. These new criteria are based on fasting plasma glucose levels, avoiding the burdensome oral glucose tolerance test (OGTT). We compared the 1997 ADA criteria with the 1985 World Health Organization (WHO) criteria with respect to the prevalence of diabetes and the cardiovascular risk profile in the population of the Hoorn Study RESEARCH DESIGN AND METHODS: The Hoorn Study is a population-based survey of 2,484 men and women, aged 50-75 years. An OGTT was performed and cardiovascular risk factors were determined in 2,378 subjects without known diabetes. Subjects were categorized according to both sets of diagnostic criteria. RESULTS: Although the prevalence of diabetes was similar for both sets of criteria, 47 of 120 (39.2%) subjects who were diagnosed with diabetes according to the 1997 ADA criteria were not classified as having diabetes when using the 1985 WHO criteria. Similarly, of 285 subjects diagnosed with impaired fasting glucose by the 1997 ADA criteria, 195 (68.4%) were classified as having normal glucose tolerance by the 1985 WHO criteria. The overall agreement was poor (kappa 0.33; 95% CI 0.28-0.38). Subjects who were diagnosed as having diabetes by either set of criteria had an adverse cardiovascular risk profile, which was between the cardiovascular risk profiles of concordant normal and concordant diabetic subjects. CONCLUSIONS: In this study both sets of criteria diagnosed a similar number of diabetic subjects, but many of the subjects shifted between glucose intolerance categories. With either set of criteria, a considerable number of subjects at risk of developing diabetes and subjects carrying an increased risk of cardiovascular disease, as reflected by an adverse cardiovascular risk profile, will be missed.     

Pharmacokinetic analysis of intra-peritoneal administration of cisplatin]

OBJECTIVE: To compare the 1997 American Diabetes Association (ADA) and the 1980-1985 World Health Organization (WHO) diagnostic criteria in categorization of the diabetes diagnostic status of adults in the U.S. RESEARCH DESIGN AND METHODS: Analyses are based on a probability sample of the U.S. population age 40-74 years in the 1988-1994 Third National Health and Nutrition Examination Survey (NHANES III). People with diabetes diagnosed before the survey were identified by questionnaire. For 2,844 people without diagnosed diabetes, fasting plasma glucose was obtained after an overnight 9 to < 24-h fast, HbA1c was measured, and a 2-h oral glucose tolerance test was administered. RESULTS: Prevalence of diagnosed diabetes in this age-group is 7.9%. Prevalence of undiagnosed diabetes is 4.4% by ADA criteria and 6.4% by WHO criteria. The net change of -2.0% occurs because 1.0% are classified as having undiagnosed diabetes by ADA criteria but have impaired or normal glucose tolerance by WHO criteria, and 3.0% are classified as having impaired fasting glucose or normal fasting glucose by ADA criteria but have undiagnosed diabetes by WHO criteria. Prevalence of impaired fasting glucose is 10.1% (ADA), compared with 15.6% for impaired glucose tolerance (WHO). For those with undiagnosed diabetes by ADA criteria, 62.1% are above the normal range for HbA1c compared with 47.1% by WHO criteria. Mean HbA1c is 7.07% for undiagnosed diabetes by ADA criteria and 6.58% by WHO criteria. CONCLUSIONS: The number of people with undiagnosed diabetes by ADA criteria is lower than that by WHO criteria. However, those individuals classified by ADA criteria are more hyperglycemic, with higher HbA1c values and a greater proportion of values above the normal range. This fact, together with the simplicity of obtaining a fasting plasma glucose value, may result in the detection of a greater proportion of people with undiagnosed diabetes in clinical practice using the new ADA diagnostic criteria.     

Diabetes in older adults: comparison of 1997 American Diabetes Association classification of diabetes mellitus with 1985 WHO classification

BACKGROUND: We aimed to compare the prevalence of abnormal glucose tolerance identified by the 1985 WHO and the 1997 American Diabetes Association (ADA) diagnostic categories based on information collected in the Cardiovascular Health Study, an epidemiological study of elderly people. METHODS: We measured glucose concentrations during fasting and 2 h after a 75 g oral glucose-tolerance test in participants aged 65-100 years in the Cardiovascular Health Study. From a 1989 cohort, we analysed the glucose measurements of 4515 individuals without a previous diagnosis of diabetes and of 262 additional measurements from an African-American cohort recruited in 1992-93. FINDINGS: In the 1989 cohort, the prevalence of untreated diabetes with ADA diagnostic fasting criteria was 7.7% versus a prevalence of 14.8% by the WHO criteria. In the African-American cohort, the prevalence of untreated diabetes was 2.7% with ADA criteria and 11.8% with WHO criteria. 3509 (77.7%) of the 4515 participants in the 1989 cohort had normal glucose concentrations according to ADA fasting criteria, compared with 2401 (53.2%) according to WHO criteria. In the African-American cohort, the corresponding numbers were 239 (91.2%) versus 153 (58.4%). All differences in prevalence of abnormal glucose tolerance between ADA and WHO classifications were significant (p<0.0001). INTERPRETATION: Among elderly individuals, there was a significant difference in the prevalence of diabetes identified by the WHO diagnostic criteria based on oral glucose-tolerance test and the ADA fasting criteria. Consequently, many individuals currently classified as non-diabetic according to ADA criteria would previously have had a diagnosis of diabetes according to WHO criteria. Longitudinal studies are needed to assess the value of the criteria in the identification of individuals at increased risk of diabetes-associated chronic complications.     

Use of the 1997 American Diabetes Association diagnostic criteria for diabetes in a Hong Kong Chinese population

OBJECTIVE: Recently, the American Diabetes Association (ADA) has proposed revised diagnostic criteria for diabetes. Lowering of the fasting plasma glucose (FPG) cutoff value is intended to reduce the discrepancy with the 2-h plasma glucose (PG) cutoff value and to encourage the use of FPG. We have applied these new criteria to data collected from a population-based prevalence survey in Hong Kong Chinese subjects of working age. RESEARCH DESIGN AND METHODS: The results of 1,513 oral glucose tolerance tests (OGTTs) from a previously published prevalence survey of glucose intolerance and cardiovascular risk factors in a Hong Kong Chinese working population were reexamined using the new criteria. Of the 1,513 subjects, 27 had a known history of diabetes. Of the remaining 1,486 subjects, 228 were also selected randomly for a second OGTT without prior knowledge of the result of the first test. RESULTS: After exclusion of the 27 subjects with a known history of diabetes, the crude prevalence of diabetes was 2.83% (n = 42) when the World Health Organization's (WHO) criteria were applied. When the criterion of FPG > or = 7.0 mmol/l was used, as recommended by the ADA, the prevalence of diabetes was 1.41% (n = 21). Twenty-nine subjects (1.95%) with FPG < 7.0 mmol/l had a 2-h PG > or = 11.1 mmol/l. Eight subjects (0.53%), previously without a diagnosis of diabetes according to the WHO criteria (FPG < 7.8 mmol/l and 2-h PG < 11.1 mmol/l), had FPG between 7.0 and 7.8 mmol/l and were classified as having diabetes by the ADA criteria. This classification gave a net change of -1.42% in the prevalence of diabetes between the use of FPG > or = 7.0 mmol/l alone and the use of WHO criteria. Among the 1,486 subjects with no known history of diabetes, those classified as having diabetes according to the ADA FPG criterion alone had higher HbA1c and fructosamine levels than diabetic subjects defined by the WHO criteria. Of the 228 subjects for whom two FPG measurements were available, those who had consistent definitions (diabetes, impaired fasting glucose, normal fasting glucose) on both occasions were considered to have reproducible tests, giving an overall reproducibility of 90.8% (207 of 228). CONCLUSIONS: Compared with the WHO criteria, the use of FPG to diagnose diabetes, as recommended by the ADA, was a more reproducible test and identified those subjects who had a greater degree of hyperglycemia. Although lowering of the cutoff value from 7.8 to 7.0 mmol/l increased the number of diagnoses among subjects with low FPG, the omission of the 2-h PG would lead to fewer subjects having their diabetes diagnosed.     

Combined use of a fasting plasma glucose concentration and HbA1c or fructosamine predicts the likelihood of having diabetes in high-risk subjects

OBJECTIVE: To assess the validity of using fasting plasma glucose (FPG) concentrations in conjunction with HbA1c or fructosamine for the screening of diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS: In this study 2,877 Hong Kong Chinese (565 [19.6%] men; 2,312 [80.4%] women) with various risk factors for glucose intolerance underwent a 75-g oral glucose tolerance test (OGTT) for screening of diabetes. The risk factors included a family history positive for diabetes, a history of gestational diabetes or impaired glucose tolerance, and obesity. RESULTS: Using World Health Organization (WHO) criteria, 1,593 (55.4%) had normal glucose tolerance, 657 (22.8%) had impaired glucose tolerance, and 627 (21.8%) had diabetes. When the 1997 American Diabetes Association (ADA) criteria were applied, 394 (13.7%) had diabetes with an FPG > or = 7.0 mmol/l. Using multiple receiver operating characteristic curve analysis, the paired values of an FPG of 5.6 mmol/l and a HbA1c of 5.5% gave an optimal sensitivity of 83.8% and specificity of 83.6% to predict a 2-h plasma glucose (PG) > or = 11.1 mmol/l. Likewise, the paired values of an FPG of 5.4 mmol/l and a fructosamine level of 235 mumol/l (n = 2,408) gave an optimal sensitivity of 81.5% and specificity of 83.2%. An FPG > or = 5.6 mmol/l and an HbA1c > or = 5.5% was 5.4-fold more likely to occur in diabetic subjects (based on the WHO criteria) compared with nondiabetic subjects. For paired parameters less than these values, the likelihood ratio of this occurring in diabetic subjects was only 0.11. Similarly, an FPG > or = 5.4 mmol/l and a fructosamine > or = 235 mumol/l was fivefold more likely to occur in diabetic subjects than in nondiabetic subjects, with both parameters less than these values having a likelihood ratio of 0.04. Using these paired values as initial screening tests, only subjects who had an FPG > or = 5.6 mmol/l and < 7.8 mmol/l and an HbA1c > or = 5.5% (n = 642) required an OGTT to confirm diabetes, thereby saving 77.7% [(2,877-642)/2,877] of the OGTTs performed. Similarly, only subjects who had an FPG > or = 5.4 mmol/l and < 7.8 mmol/l and a fructosamine > or = 235 mumol/l (n = 526) required OGTT to confirm diabetes, meaning that 78.2% [(2,408-526)/2,408] of the OGTTs could have been saved. Based on the 1997 ADA criterion of an FPG cutoff value of 7.0 mmol/l, the corresponding numbers of OGTTs to be saved were 82.6% and 85.5%, respectively. CONCLUSIONS: The paired values of FPG and HbA1c or FPG and fructosamine helped to identify potentially diabetic subjects, the diagnosis of which could be further confirmed by the 75-g OGTT. Using this approach approximately 80% of OGTTs could have been saved, depending on the diagnostic cutoff value of FPG.     

High glycosylated hemoglobin levels increase the risk of progression to diabetes mellitus in subjects with glucose intolerance

The relationships between HbA1c level and oral glucose tolerance test (OGTT) at the initial visit and the incidence of diabetes after 5 years of follow-up were investigated in 819 subjects participating in a general health examination. The 100 g OGTT was performed. In order to use WHO criteria, the blood glucose levels of 100 g OGTT corresponding to those of 75 g OGTT were adopted according to the recommendations of the Japan Diabetes Society. Subjects other than diabetic type and IGT (impaired glucose tolerance) were divided into a normal group (fasting blood glucose < 100 mg/dl, 1-h blood glucose < 160 mg/dl, a 2-h blood glucose < 120 mg/dl) and a borderline group (the remaining subjects). In IGT, the incidence of diabetes in the low- (< or = 6.3%), intermediate- (6.4-6.7%) and high-HbA1c (> of = 6.8%) groups were 10.4%, 23.1% and 52.5%, respectively (high vs intermediate and low, P < 0.001; intermediate vs low, P < 0.05). In the borderline group, the incidence were 2.8%, 14.3% and 28.6%, respectively (high and intermediate vs low, P < 0.001). The results showed that the combination of HbA1c level and OGTT enables more precise prediction of progression to NIDDM in subjects with glucose intolerance.     

The STOP-NIDDM Trial: an international study on the efficacy of an alpha-glucosidase inhibitor to prevent type 2 diabetes in a population with impaired glucose tolerance: rationale, design, and preliminary screening data. Study to Prevent Non-Insulin-Dependent Diabetes Mellitus

OBJECTIVE: To describe the rationale and design, and to discuss the preliminary screening data, of the Study to Prevent NIDDM (STOP-NIDDM Trial), an international study on the efficacy of the alpha-glucosidase inhibitor acarbose in preventing or delaying the development of type 2 diabetes in a population with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: A total of 1,418 subjects diagnosed with IGT according to the World Health Organization's criteria and having a fasting plasma glucose concentration > or =5.6 mmol/L were randomized in a double-blind fashion to receive either acarbose (100 mg t.i.d.) or placebo for a predictive median follow-up period of 3.9 years. The primary outcome is the development of type 2 diabetes diagnosed using a 75-g oral glucose tolerance test according to the new criteria. The secondary outcomes are changes in blood pressure, lipid profile, insulin sensitivity, cardiovascular events, and morphometric profile. RESULTS: Screening was performed in a high-risk population. As of 1 March 1997, 4,424 subjects had been screened, and data were available for 3,919 (88.5%) subjects. Of these subjects, 1,200 (30.6%) had glucose intolerance. Of the subjects with glucose intolerance, 521 (13.3%) had previously undetected type 2 diabetes, and 679 (17.3%) had IGT. Of the IGT population, 412 (60.7%) subjects were eligible for the study This population had the following characteristics: the mean age was 54.8 years, 52% of the subjects were female, 53% had more than one risk factor for type 2 diabetes, >90% had a family history of diabetes, 78.2% had a BMI > or =27 kg/m2, 47.5% had high blood pressure, 51.2% had dyslipidemia, and 22.8% of the women had a history of gestational diabetes. CONCLUSIONS: Screening of a high-risk population yields one eligible subject per every 10 volunteers screened. This study should definitely answer the question of whether acarbose can prevent or delay the progression of IGT to type 2 diabetes mellitus.     

Reversion from type 2 diabetes to nondiabetic status. Influence of the 1997 American Diabetes Association criteria

OBJECTIVE: To determine the incidence and the rate of reversion of type 2 diabetes to a nondiabetic status in the 7- to 8-year follow-up of the San Antonio Heart Study, and to determine the influence of the recent 1997 American Diabetes Association (ADA) criteria for diabetes on these rates. Individuals who revert have been problematic for those developing criteria for the diagnosis of type 2 diabetes. Few studies have addressed this issue using 1979 National Diabetes Data Group/1980 World Health Organization (WHO) criteria. RESEARCH DESIGN AND METHODS: We studied 3,682 Mexican-American and non-Hispanic white men and nonpregnant women who completed both the baseline and follow-up examination of the San Antonio Heart Study. Incidence and reversion rates were calculated using both the 1980 WHO and the 1997 ADA criteria. Risk factors for reversion were identified, and the best fitting model using multiple logistic regression was determined using both the 1980 WHO and the 1997 ADA criteria. RESULTS: Using the 1997 ADA criteria, the age-adjusted incidences of type 2 diabetes for Mexican-American men and women were 10.8 and 12.2%, respectively. For non-Hispanic white men and women, the age-adjusted incidence rates were 5.5 and 5.1%, respectively. Similar age-adjusted incidences were recorded using the 1980 WHO criteria. The reversion rate for individuals with type 2 diabetes was 11.5% using the 1980 WHO criteria and 12.5% using the 1997 ADA criteria. These rates were not significantly different. Numerous risk factors for reversion were identified. The best fitting model, after controlling for age, sex, and ethnicity, included baseline 2-h glucose level, baseline HDL cholesterol, and previous diagnosis of diabetes. The models were the same for both the 1980 WHO and the 1997 ADA criteria. CONCLUSIONS: There was no significant difference in the incidence or the reversion rates for diabetic subjects using either 1980 WHO or 1997 ADA criteria. In addition, the risk factors for reversion were very similar using either set of criteria. The revision of the ADA criteria did not have a significant influence on reversion in this study.     

Thrombolytic eligibility

OBJECTIVE: To evaluate the prevalence and time trends for diagnosed and undiagnosed diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults by age, sex, and race or ethnic group, based on data from the Third National Health and Nutrition Examination Survey, 1988-1994 (NHANES III) and prior Health and Nutrition Examination Surveys (HANESs). RESEARCH DESIGN AND METHODS: NHANES III contained a probability sample of 18,825 U.S. adults > or = 20 years of age who were interviewed to ascertain a medical history of diagnosed diabetes, a subsample of 6,587 adults for whom fasting plasma glucose values were obtained, and a subsample of 2,844 adults between 40 and 74 years of age who received an oral glucose tolerance test. The Second National Health and Nutrition Examination Survey, 1976-1980, and Hispanic HANES used similar procedures to ascertain diabetes. Prevalence was calculated using the 1997 American Diabetes Association fasting plasma glucose criteria and the 1980-1985 World Health Organization (WHO) oral glucose tolerance test criteria. RESULTS: Prevalence of diagnosed diabetes in 1988-1994 was estimated to be 5.1% for U.S. adults > or = 20 years of age (10.2 million people when extrapolated to the 1997 U.S. population). Using American Diabetes Association criteria, the prevalence of undiagnosed diabetes (fasting plasma glucose > or = 126 mg/dl) was 2.7% (5.4 million), and the prevalence of impaired fasting glucose (110 to < 126 mg/dl) was 6.9% (13.4 million). There were similar rates of diabetes for men and women, but the rates for non-Hispanic blacks and Mexican-Americans were 1.6 and 1.9 times the rate for non-Hispanic whites. Based on American Diabetes Association criteria, prevalence of diabetes (diagnosed plus undiagnosed) in the total population of people who were 40-74 years of age increased from 8.9% in the period 1976-1980 to 12.3% by 1988-1994. A similar increase was found when WHO criteria were applied (11.4 and 14.3%). CONCLUSIONS: The high rates of abnormal fasting and postchallenge glucose found in NHANES III, together with the increasing frequency of obesity and sedentary lifestyles in the population, make it likely that diabetes will continue to be a major health problem in the U.S.     

Incidence of diabetes mellitus in women following impaired glucose tolerance in pregnancy is lower than following impaired glucose tolerance in the non-pregnant state

Impaired glucose tolerance (IGT), which is asymptomatic and requires a glucose tolerance test for detection, is a well-known risk factor for diabetes mellitus. Outside the research setting it is rarely identified in people who lack specific risk factors for diabetes except during pregnancy, at which time screening with an oral glucose challenge is a routine procedure. A 75-g oral glucose tolerance test was performed during the latter part of pregnancy or during a routine epidemiology survey in 15-39-year-old Pima Indian women with no history of abnormal glucose tolerance. Those with IGT by World Health Organization criteria were included in this study. Diabetes incidence in women was compared between those whose IGT was first detected during pregnancy and those who were not pregnant when IGT was first recognized. Seventeen of 73 pregnant women and 114 of 244 non-pregnant women developed diabetes within 10 years. When controlled for plasma glucose concentration, age, body mass index, parity and duration of follow-up, those who were not pregnant were at higher risk of developing diabetes than those who were pregnant (hazard rate ratio = 1.71, 95% confidence interval = 1.01-2.91). Previous studies had reported that women with IGT during pregnancy are at higher risk of diabetes than women with normal glucose tolerance. This study suggests that women with IGT during pregnancy are at lower risk than non-pregnant women with a similar plasma glucose concentration who, in the clinical setting, are likely to remain unrecognized.     

Epidemiology of diabetes mellitus in the elderly in northern Greece: a population study

This population based study was undertaken to ascertain the overall prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in the elderly using the WHO criteria. The role of obesity in the development of DM or IGT has been investigated for both sexes per decade of age. Furthermore the potential for DM to increase with age, as has been suggested before, has been evaluated using the IGT as a proportion of total glucose intolerance (IGT/TGI) for the same parts of the tested sample. From the 647 persons registered as elderly people in a small town in northern Greece (total population 5875 people), 66 persons did not participate in this survey. Fifty-six subjects (9.7%) had previously diagnosed DM. The remainder were tested using fasting blood glucose measurements or an oral glucose tolerance test (OGTT). The prevalence of previously undiagnosed DM according to fasting blood glucose values or after 2 h of 75 g load values was 10.1% and 9.3%, respectively. Thus the overall prevalence of DM was 29.1% and of IGT was 15.1%. These data support an increased frequency of DM (65% previously undiagnosed) and IGT in the elderly, whereas this population's susceptibility seems to decline in the older groups for both sexes. Obesity remains a risk factor for DM and IGT particularly among the younger groups although its role has been found to decline with age.     

Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women

We examined antepartum clinical characteristics along with measures of glucose tolerance, insulin sensitivity, pancreatic beta-cell function, and body composition in Latino women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes or impaired glucose tolerance (IGT) within 6 months after delivery. A total of 122 islet cell antibody-negative women underwent oral and intravenous glucose tolerance tests (OGTT; IVGTT), hyperinsulinemic-euglycemic clamps, and measurement of body fat between 29 and 36 weeks' gestation and returned between 1 and 6 months postpartum for a 75-g OGTT. Logistic regression analysis was used to examine the relationship between antepartum variables and glucose tolerance status postpartum. At postpartum testing, 40% of the cohort had normal glucose tolerance, 50% had IGT, and 10% had diabetes by American Diabetes Association criteria. Independent antepartum predictors of postpartum diabetes were the 30-min incremental insulin:glucose ratio during a 75-g OGTT (P = 0.0002) and the total area under the diagnostic 100-g glucose tolerance curve (P = 0.003). Independent predictors of postpartum IGT were a low first-phase IVGTT insulin response (P = 0.0001), a diagnosis of GDM before 22 weeks' gestation (P = 0.003), and weight gain between prepregnancy and the postpartum examination (P = 0.03). All subjects had low insulin sensitivity during late pregnancy, but neither glucose clamp nor minimal model measures of insulin sensitivity in the 3rd trimester were associated with the risk of IGT or diabetes within 6 months' postpartum. These results highlight the importance of pancreatic beta-cell dysfunction, detectable under conditions of marked insulin resistance in late pregnancy, to predict abnormalities of glucose tolerance soon after delivery in pregnancies complicated by GDM. Moreover, the association of postpartum IGT with weight gain and an early gestational age at diagnosis of GDM suggests a role for chronic insulin resistance in mediating hyperglycemia outside the 3rd trimester in women with such a beta-cell defect.     

Prevalence of retinopathy in people with diabetes, impaired glucose tolerance, and normal glucose tolerance

OBJECTIVE: Recently, an international expert committee published new revised criteria for diagnosing diabetes. According to the new criteria, the 2-h glucose level for diabetes in the oral glucose tolerance test (OGTT) is the same as in the previous World Health Organization criteria, but the cut point for the fasting blood glucose level has been lowered to be equivalent to the 2-h OGTT level. Measurement of the fasting blood glucose level is preferred to the 2-h OGTT glucose level. The ability of the new cut point for fasting blood glucose to discriminate between those at a high and a low risk for retinopathy was tested in a population-based study RESEARCH DESIGN AND METHODS: The population consisted of all the 1,008 subjects (456 men) born in 1935 and living in a Finnish city A screening for type 2 diabetes was carried out in the first phase. All participants who were not on antidiabetic medication were invited for an OGTT in the second phase. A fasting blood glucose value was measured from the diabetic subjects on antidiabetic medication. In addition, measurements of serum cholesterol, HDL cholesterol, and triglycerides were made, and fundus photographs were taken. Altogether, 831 subjects (368 men) (82%) participated and constitute the eligible study population for the present analyses. Fundus photographs were available for 790 subjects (347 men) (95%). RESULTS: There were 28 subjects (3.5%) who had mild retinopathic changes in the fundus photographs. Retinopathic changes were associated with higher fasting blood glucose levels, but not with any of the other background factors. The prevalence of retinopathy was 10.2% (95% CI 4.8-18.5) in subjects with a fasting blood glucose of > or =6.1 mmol/l, while it was 2.6% (1.5-4.0) in those with a lower fasting blood glucose level. In the former group, a majority (seven of nine) of the subjects with retinopathy were previously diagnosed diabetic patients. Some cases of retinopathy were found regardless the level of glycemia, and measurement of the 2-h OGTT glucose levels did not increase information. CONCLUSIONS: The results of this population study give support to the use of fasting blood glucose levels in diagnosing type 2 diabetes. The lower limit of the highest decile of the fasting glucose level was 6.1 mmol/l, and it discriminated subjects at a high risk for retinopathy from those at a low risk. Because of the limited number of subjects with retinopathy in this study, the level of hyperglycemia associated with retinopathy cannot be estimated accurately.     

Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study

OBJECTIVE: To assess whether people with impaired glucose tolerance (IGT) exhibit an increased risk of atherosclerosis as measured by the thickness of the carotid artery. RESEARCH DESIGN AND METHODS: We examined the relationship between glucose tolerance status and subclinical atherosclerosis in the Insulin Resistance Atherosclerosis Study (IRAS). The IRAS is an epidemiological study of 1,625 Hispanic, African-American, and white men and women, with approximately equal numbers of subjects with normal glucose tolerance (NGT), IGT, and type 2 diabetes as assessed by an oral glucose tolerance test. Half of those with diabetes were previously unaware of their condition and were defined as having new diabetes. Persons using insulin were excluded. The intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA) was measured as an index of subclinical atherosclerosis using B-mode ultrasonography. RESULTS: Adjusted for demographics and smoking, CCA-IMT increased most notably at the level of established diabetes (802, 822, 831, and 896 microm for NGT, IGT, new diabetes, and established diabetes, respectively). Adjustment for coronary heart disease (CHD) risk factors, which tended to worsen across glucose tolerance category, further minimized the slightly graded relationship. The relationship with the ICA-IMT was steeper and again suggested that the increased wall thickness is associated with diabetes, not with IGT. The relationship between glucose tolerance category and IMT was similar in men and women. CONCLUSIONS: We observed considerably greater IMT among persons with established diabetes but no significant increase in persons with IGT. These data suggest that the increased risk of CHD observed in persons with diabetes may largely develop after the onset of overt diabetes.     

Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults. WHO Ad Hoc Diabetes Reporting Group

OBJECTIVE: To assemble standardized estimates of abnormal glucose tolerance in adults in diverse communities worldwide and provide guidelines for the derivation of comparable estimates in future epidemiological studies. RESEARCH DESIGN AND METHODS: The project was limited to population-based investigations that had used current WHO criteria for diagnosis and classification of abnormal glucose tolerance. Raw data were obtained by WHO from surveys conducted during 1976-1991 of over 150,000 persons from 75 communities in 32 countries. Data within the truncated age range of 30-64 yr were adjusted to the standard world population of Segi. Age-specific prevalences also are reported for selected populations. RESULTS: Within the chosen age range, diabetes was absent or rare (< 3%) in some traditional communities in developing countries. In European populations, age-standardized prevalence varied from 3 to 10%. Some Arab, migrant Asian Indian, Chinese, and Hispanic American populations were at higher risk with prevalences of 14-20%. The highest prevalences were found in the Nauruans (41%) and the Pima/Papago Indians (50%). Age-standardized prevalence of IGT was low (< 3%) in some Chinese, traditional American Indian, and Pacific island populations. Moderate (3-10%) or high (11-20%) prevalences of IGT were observed in many populations worldwide. The highest estimates for prevalence of IGT were seen in female Muslim Asian Indians in Tanzania (32%) and in urban male Micronesians in Kiribati (28%). Prevalence of diabetes rose with age in all populations in which age-specific data were examined. This trend was most pronounced in those at moderate to high risk. The ratio of prevalence of diabetes in men versus women varied markedly between populations with little discernable trend, although IGT was generally more common in women. In most communities, at least 20% of diabetes cases were unknown before the survey, and in many communities, > 50% were previously undiagnosed. In both Chinese and Indian migrant populations, relative prevalence was high when compared with indigenous communities. CONCLUSIONS: Diabetes in adults is now a global health problem, and populations of developing countries, minority groups, and disadvantaged communities in industrialized countries now face the greatest risk.     

Cardiovascular risk factors prior to the development of non-insulin-dependent diabetes mellitus in persons with impaired glucose tolerance: the Hoorn Study

The aim of the study was to analyze cardiovascular risk factors as predictors for developing non-insulin-dependent diabetes mellitus (NIDDM) in people with impaired glucose tolerance. A cross-sectional survey of glucose tolerance was conducted in people, aged 50-74, who were randomly selected from the registry of the middle-sized town Hoorn (The Netherlands). Based on the mean values of two oral glucose tolerance tests, people were classified in glucose tolerance categories according to the WHO criteria. The mean follow-up time was 36 months (range 13-55 months). The cumulative incidence of NIDDM was 34% (95% CI 16.9-45.1). In multiple logistic regression analysis, cardiovascular risk factors at baseline did not predict the conversion from impaired glucose tolerance to NIDDM, in contrast with the two-hour plasma glucose level (odds ratio 3.56, p < 0.001) and the fasting proinsulin level, as one of the determinants of beta-cell dysfunction (Odds ratio 2.1, p < 0.05). The baseline HDL-cholesterol level, one of the components of the insulin resistance syndrome, was associated with the conversion from impaired glucose tolerance to normal glucose tolerance (Odds ratio 1.58, p < 0.05). The results of our study seem to support the hypothesis that conversion from impaired glucose tolerance to normal glucose tolerance depends on insulin resistance and the development of NIDDM from impaired glucose tolerance depends on beta-cell dysfunction.     

Glucose intolerance and associated factors in the Fergana Valley, Uzbekistan

Prevalence of glucose intolerance and other noncommunicable diseases has been examined in subjects aged 35 years and over in semirural and urban communities in the Fergana Valley in the eastern part of Uzbekistan, Central Asia. Diabetes and impaired glucose tolerance (IGT) were diagnosed according to the recommendations of the latest WHO Study Group on diabetes. Crude prevalence of diabetes was 9% and 5%, respectively, in semirural men and women, 13% and 9% in urban men and women. Crude prevalence of impaired glucose tolerance (IGT) was 6% and 9%, respectively, in semirural men and women, 9% and 8% in urban men and women. After adjustment for non-response, prevalence of diabetes was 5% and 4%, respectively, in semirural men and women and 8% in both urban men and women. Adjusted prevalence of IGT was 4% and 8%, respectively, in semirural men and women, 5% and 6% in urban men and women. The majority of subjects with a prior diagnosis of diabetes were being treated with oral hypoglycaemic agents. Almost one-half of subjects in both communities had body mass index of 25 kg m(-2) or greater. Central obesity (waist-hip ratio 0.95 or greater for men, 0.85 or greater for women) was observed in over one-quarter of subjects in both communities. Clinical hypertension was not frequent by international standards (9% in semirural subjects and 13% in urban subjects) but a number of subjects who were clinically normotensive claimed to be taking antihypertensive medication. It is concluded that glucose intolerance and central obesity are common in this region of Uzbekistan, about which there was previously little information.     

Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance

Impaired glucose tolerance (IGT) is associated with defects in both insulin secretion and action and carries a high risk for conversion to non-insulin-dependent diabetes mellitus (NIDDM). Troglitazone, an insulin sensitizing agent, reduces glucose concentrations in subjects with NIDDM and IGT but is not known to affect insulin secretion. We sought to determine the role of beta cell function in mediating improved glucose tolerance. Obese subjects with IGT received 12 wk of either 400 mg daily of troglitazone (n = 14) or placebo (n = 7) in a randomized, double-blind design. Study measures at baseline and after treatment were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin sensitivity index (SI) assessed by a frequently sampled intravenous glucose tolerance test, insulin secretion rates during a graded glucose infusion, and beta cell glucose-sensing ability during an oscillatory glucose infusion. Troglitazone reduced integrated glucose and insulin responses to oral glucose by 10% (P = 0.03) and 39% (P = 0.003), respectively. SI increased from 1.3+/-0.3 to 2.6+/-0.4 x 10(-)5min-1pM-1 (P = 0.005). Average insulin secretion rates adjusted for SI over the glucose interval 5-11 mmol/liter were increased by 52% (P = 0.02), and the ability of the beta cell to entrain to an exogenous oscillatory glucose infusion, as evaluated by analysis of spectral power, was improved by 49% (P = 0.04). No significant changes in these parameters were demonstrated in the placebo group. In addition to increasing insulin sensitivity, we demonstrate that troglitazone improves the reduced beta cell response to glucose characteristic of subjects with IGT. This appears to be an important factor in the observed improvement in glucose tolerance.     

Prevalence and incidence of NIDDM in Daqing City

OBJECTIVE: To investigate the prevalence and incidence of non-insulin dependent diabetes (NIDDM) in China by WHO criteria. METHODS: In the prevalence survey of NIDDM all 110660 participants (55391 men, 53269 women) were inhabitants of Daqing City, the largest oil center in northeast China, accounting for 87.3% of the 25 to 74 aged population in this city. They were screened by measuring two-hour plasma glucose concentrations (PG2 h) after a breakfast containing at least 80 g of carbohydrate, then a standard oral glucose tolerance test (OGTT, 75 g glucose load) was performed in 4209 subjects with PG2 h more than 6.67 mmol/L in this screen. NIDDM and impaired glucose tolerance (IGT) were diagnosed using WHO criteria. Incidence survey was made in 36471 non-diabetics identified in the prevalence survey. Two-hour urine-glucose after breakfast was determined during first screen. The urine-glucose trace or positive subjects were then followed by OGTT. Glucose was measured by glucose oxidation method. RESULTS AND CONCLUSIONS: In prevalence survey, 630 newly diagnosed NIDDM (296 males, 334 females) and 596 IGT (318 males, 278 females) were found in 110660 (male:female = 55391/53269) studied subjects in addition to 190 previously diagnosed NIDDM. Thus the total prevalence of NIDDM was 7.7/1000, and IGT was 5.5/1000. Standardized to the Chinese population in 1982, the prevalences are 12.6/1000 (95% CI = 12.0/1000-13.3/1000) and 7.7/1000 (95% CI = 7.16/1000-8.19/1000) respectively. In the incidence survey, 191 NIDDM (103 males, 88 females) were diagnosed in the 36471 (male:female = 18801/17670) non-diabetics from 1986 to 1990, thus the annual incidence of NIDDM was 131/100000 (137 males, 125 females). Standardized incidence is 131/100000 (95% CI = 94/100000-168/ 100000). It is estimated that there would be more than 700 thousand new diabetics per year in 24-74 years old Chinese if Chinese population were 1.3 billion in the early 21st century.