A high concentration of fasting plasma non-esterified fatty acids is a risk factor for the development of NIDDM

Summary To assess the role of fasting plasma non-esterified fatty acids (NEFA) in the development of non-insulin-dependent diabetes mellitus (NIDDM), data were analysed from annual examinations of 190 non-diabetic Pima Indians. Glucose tolerance was measured by a 75-g oral glucose tolerance test, insulin action by a euglycaemic hyperinsulinaemic (40 mU · m^–2 · min^–1) clamp and in vitro lipolysis using isolated abdominal fat cells. After a mean follow-up period of 4.0±2.4 years (mean ± SD), 47 subjects developed NIDDM. Risk factors for NIDDM were estimated by proportional-hazards analysis and risk ratios (RR) with 95% confidence intervals (95% CI) calculated at the 90th and 10th percentile of the predictor variables. A large average fat-cell volume was predictive of NIDDM (RR=2.4; 95% CI=1.2–4.8) independent of age, sex, percent body fat and body fat distribution. A high fasting plasma NEFA concentration was also a risk factor for NIDDM (RR=2.3; 95% CI=1.1–4.7) independent of sex, percent body fat, waist/thigh ratio, insulin-mediated glucose uptake and fasting triglyceride concentration. We conclude that large fat cells and the resulting increased plasma NEFA concentrations are risk factors for the development of NIDDM.Abbreviations NEFA Non-esterified fatty acids - NIDDM non-insulin-dependent diabetes mellitus - CI confidence interval - RR risk ratio     

Glucose intolerance,hyperinsulinaemia and cognitive function in a general population of elderly men

Summary Cognitive impairment is highly prevalent among the elderly. Subjects with disturbed glucose metabolism may be at risk of impaired cognitive function, as these disturbances can influence cognition through atherosclerosis, thrombosis and hypertension. We therefore studied the cross-sectional association of cognitive function with hyperinsulinaemia, impaired glucose tolerance and diabetes mellitus in a population-based cohort of 462 men aged 69 to 89 years. Cognitive function was measured by the 30-point Mini-Mental State Examination. Results were expressed as the rate ratio (95% confidence interval) of the number of erroneous answers given on the Mini-Mental State Examination by the index compared to the reference group. Compared to subjects with normal glucose tolerance, known diabetic patients had a rate ratio of 1.23 (1.04–1.46), newly-diagnosed diabetic patients of 1.16 (0.91–1.48) and subjects with impaired glucose tolerance of 1.18 (0.98–1.41), after adjustment for confounding due to age, occupation and cigarette smoking (p-trend=0.01). Non-diabetic subjects in the highest compared to the lowest quartile of the area under the insulin curve had a rate ratio of 1.24 (1.03–1.50), after adjustment for confounding (p-trend=0.02). The results did not change appreciably when potentially mediating factors, including cardiovascular diseases and risk factors associated with the insulin resistance syndrome, were taken into account. These results suggest that diabetes, as well as impaired glucose tolerance and hyperinsulinaemia in non-diabetic subjects are associated with cognitive impairment.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - MMSE Mini-Mental State Examination - CI confidence interval - RR rate ratio     

Fasting proinsulin and 2-h post-load glucose levels predict the conversion to NIDDM in subjects with impaired glucose tolerance: The Hoorn Study

Summary The aims of the present study were to observe the natural history of impaired glucose tolerance and to identify predictors for development of non-insulin-dependent diabetes mellitus (NIDDM). A survey of glucose tolerance was conducted in subjects aged 50–74 years, randomly selected from the registry of the middle-sized town of Hoorn in the Netherlands. Based on the mean values of two oral glucose tolerance tests subjects were classified in categories of glucose tolerance according to the World Health Organization criteria. All subjects with impaired glucose tolerance (n=224) were invited to participate in the present study, in which 70% (n=158) were subsequently enrolled. During follow-up subjects underwent a repeated paired oral glucose tolerance test. The mean follow-up time was 24 months (range 12–36 months). The cumulative incidence of NIDDM was 28.5% (95% confidence interval 15–42%). Age, sex, and anthropometric and metabolic characteristics at baseline were analysed simultaneously as potential predictors of conversion to NIDDM using multiple logistic regression. The initial 2-h post-load plasma glucose levels and the fasting proinsulin levels were significantly (p<0.05) related to the incidence of NIDDM. Anthropometric characteristics, the 2-h post-load specific insulin levels and the fasting proinsulin/fasting insulin ratio were not related to the incidence of NIDDM. These results suggest that beta-cell dysfunction rather than insulin resistance plays the most important role in the future development of diabetes in a high-risk Caucasian population.Abbreviations IGT Impaired glucose tolerance - NIDDM non-insulin-dependent diabetes mellitus - OGTT oral glucose tolerance test - CI confidence interval - W/H ratio waist/hip ratio - BMI body mass index - OR odds ratio     

Impaired glucose tolerance in a middle-aged male urban population: a new approach for identifying high-risk cases

Summary From an urban population (n=9,033) of 47–49-year-old males, 6,956 participated in a multiphase screening programme, of whom 1.5% were already registered as diabetic patients, 1.7% were then found to be diabetic; of 6,325 subjects given oral glucose tolerance tests, 6.6% were found to have impaired glucose tolerance (WHO criteria, 1985). In 889 asymptomatic cases with initial capillary whole blood glucose values 6.6 mmol/l fasting and/or 2 h postload, fluctuation in oral glucose tolerance was studied at repeat tests within one month; the mean differences in glucose values between the first and second test were <–1% (fasting) and –15% (2 h post-load); there were no differences in body weight, and 62% of those with initially impaired glucose tolerance had normalised by the repeat test. Only in 109 cases (1.7%) were 2 h post-load values in the 7.8–11.0 mmol/l range both at the first and the repeat test; these cases were comparable vis-à-vis body mass index, triceps skin fold, blood pressure and initial glucose and insulin values, but had significantly lower oxygen uptake (2.34±0.54 l/min vs 2.63±0.681/min; p<0.003), as compared with subjects with initially impaired glucose tolerance but normal repeat test outcome. However, subjects with high normal first test results (2 h value in the 7.0–7.7 mmol/l range) and second test results in the 7.0–11.0 mmol/l range, resembled those with persistent impairment of glucose tolerance in all respects (including oxygen uptake). The repeat test procedure (including ergometry), is therefore to be recommended in selecting true risk cases.     

Diabetes screening after gestational diabetes mellitus: poor performance of fasting plasma glucose

Abstract. Gestational diabetes mellitus (GDM) is an established risk factor for the development of overt diabetes. Since the change in diagnostic criteria for diabetes in 1997, it is unclear whether there should be any preference for fasting or post-glucose challenge blood glucose in diagnosing diabetes after GDM. The study aimed at assessing the usefulness of both diagnostic methods in women after GDM. The study enrolled 193 women with previous GDM. Women who did not have a current diagnosis of diabetes were screened for impaired fasting glucose (IFG) and for glucose intolerance with an oral 75-g glucose tolerance test. A total of 45 (23.3%) subjects declared to be already diabetic. Of the 148 non-diabetic subjects, 141 (95.3%) had normal fasting plasma glucose, whereas four (2.8%) had IFG (i.e. FPG6.1 and <7.0 mmol/l) and 3 (2.5%) had FPG7.0 mmol/l. Upon OGTT, among the 141 subjects with normal FPG, 6 (4.3%) were diagnosed with diabetes and 23 (16.3%) with impaired glucose tolerance (IGT); the remaining 112 (79.5%) had normal glucose tolerance. Three out of four subjects with IFG had IGT. The sensitivities of fasting criteria for diagnosis of diabetes and IFG/IGT were 14.3% (95% CI, 8.0%–37.2%) and 17.1% (95% CI, 8.6%–19.8%), respectively. The specificities were 98.6% (95% CI, 97.9%–99.7%) and 99.1% (95% CI, 96.5%–100%), respectively. The kappa for diabetes diagnosis was 0.177 (95% CI, 0.018–0.507). For women with previous GDM, the sensitivity of the new criteria based upon fasting plasma glucose is unacceptably low. In addition, the two sets of criteria are not interchangeable. Therefore, we suggest full glucose tolerance diagnostic procedures in women after GDM, including assessment of post-glucose challenge values.     

Association between a deletion/insertion polymorphism in the α2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study

Aims/hypothesis Impaired insulin secretion has a strong genetic component. In this study we investigated whether the 12Glu9 polymorphism in the gene encoding the 2B-adrenergic receptor (ADRA2B) is associated with insulin secretion and/or the incidence of Type 2 diabetes in individuals with impaired glucose tolerance.Methods We investigated a total of 506 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study (DPS). Participants were randomly assigned to an intervention group or a control group. Anthropometric measurements and an oral glucose tolerance test were performed at baseline and at annual follow-up. In a subgroup of patients (n=83), a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at baseline.Results All patients had similar anthropometric measurements and insulin and glucose levels at baseline. Multiple logistic regression analysis revealed significant interaction (p=0.003) between study group and genotype across the entire study population. In the control group, subjects with the Glu9 allele had an increased risk of developing Type 2 diabetes compared with subjects with the Glu12/12 genotype (odds ratio [OR]=2.68, 95% CI 1.02–7.09, p=0.047 for Glu12/12, and OR=5.17, 95% CI 1.76–15.21, p=0.003 for Glu9/9). This increased risk was not observed in the intervention group, who showed significant weight loss during the trial. In the subgroup who underwent the FSIGT, subjects with the Glu9/9 genotype showed the lowest acute insulin response (p=0.005 for trend).Conclusions/interpretation The 12Glu9 polymorphism of ADRA2B is associated with impaired first-phase insulin secretion and may predict the development of Type 2 diabetes in subjects with impaired glucose tolerance who are not subjected to a lifestyle intervention.Abbreviations AIR acute insulin response - AR adrenergic receptor - BMR basal metabolic rate - DI disposition index - DPS the Finnish Diabetes Prevention Study - FSIGT frequently sampled intravenous glucose tolerance test - OR odds ratio - S_G glucose effectiveness - S_I insulin sensitivity index     

Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance

Summary Recent evidence suggests that the post-prandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion ( 0–10 min insulin area ÷ 0–10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2–19.4] vs 9.1 [2.6–14.5] mU·mmol^–1; p<0.01). During the clamp, circulating insulin (93±8 [mean±SEM] and 81±10 mU·l^–1) and glucagon (54±4 and 44±6 ng·l^–1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78±0.27 vs 4.47±0.53 mg·kg^–1·min^–1; p<0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38±0.10 and 0.30±0.18 mg·kg^–1·min^–1). Therefore, the main defects in subjects with impaired glucose tolerance are decreased first phase insulin secretion and peripheral non-oxidative glucose disposal, but hepatic glucose output shows normal responsiveness to insulin.Abbreviations FPIS First phase insulin secretion - PG plasma glucose - NIDDM non-insulin-dependent diabetes mellitus - IGT impaired glucose tolerance - HGO hepatic glucose output - IVGTT intravenous glucose tolerance test - OGTT oral glucose tolerance test     

The natural history of impaired glucose tolerance in the Micronesian population of Nauru: A six-year follow-up study

Summary A longitudinal study of 266 randomly selected non-diabetic Nauruans (215 normal subjects, 51 with impaired glucose tolerance) has permitted the natural history of impaired glucose tolerance to be studied in this Micronesian population. Nauruans are known to suffer from a very high prevalence of abnormal glucose tolerance. The subjects were first examined in 1975–1976, and a follow-up examination was performed in 1982. Of the subjects with impaired glucose tolerance, 26% developed diabetes during the study period (4% per annum) compared with 7% of normal subjects (1% per annum). After controlling for the effects of both age and obesity, the risk of subsequent diabetes for subjects with impaired glucose tolerance remained significantly higher than for normal subjects (odds ratio 3.6, 95% confidence interval 1.4–9.1). Of those with impaired glucose tolerance on initial examination, 39% were normoglycaemic at follow-up. In subjects with impaired glucose tolerance, of nine factors examined only plasma glucose concentration at the time of the initial examination was consistent in predicting progression to diabetes, when the data were examined by both univariate and multivariate methods. Both 2-h and fasting plasma glucose values were useful predictors. Thus, Nauruans with impaired glucose tolerance have a higher risk of subsequent diabetes than their normoglycaemic counterparts, after controlling for age and obesity. Nevertheless, the prognosis of impaired glucose tolerance is unpredictable as a substantial proportion of such subjects return to normality. Plasma glucose concentration is the most important predictor of subsequent diabetes. These results accord with recent findings from longitudinal studies of impaired glucose tolerance in other populations.     

Hyperinsulinaemia in youth is a predictor of Type 2 (non-insulin-dependent) diabetes mellitus

Summary This study aimed to compare plasma insulin concentrations across the age-range from childhood to old age in the populations of Nauru and Tuvalu, and to assess their relationship to the incidence of impaired glucose tolerance and diabetes in young Nauruans. The studies, performed in 1975 and 1976, found that Nauru had a higher prevalence of Type 2 (non-insulin-dependent) diabetes mellitus than Tuvalu. Both studies included subjects of 8–29 years of age (n=320 in Nauru, n=318 in Tuvalu) and on these subjects glucose tolerance status, body mass index and fasting and 2-h (post 75 g glucose load) plasma insulin concentrations were determined. In Nauru, follow-up surveys in 1982 and 1987 included many of the subjects first seen in 1975/1976, allowing the incidence and natural history of glucose intolerance to be studied. Within the group of subjects with normal glucose tolerance, there was no effect of age on plasma insulin distributions in either population. However, in both populations, 8–19 year old subjects with normal glucose tolerance had higher body mass index-adjusted geometric mean fasting and 2-h insulin concentrations than older age-groups (p < 0.001 for fasting insulin). Body mass index-adjusted geometric mean 2-h plasma insulin was higher in subjects with abnormal glucose tolerance relative to those with normal glucose tolerance in both populations. In Nauruans, 2-h insulin levels at baseline were predictive of impaired glucose tolerance and Type 2 diabetes in 1982, and fasting and 2-h insulin levels predicted development of Type 2 diabetes in 1987. Hyperinsulinaemia in the presence of normal glucose tolerance is evident in young people in Nauru and Tuvalu, as has been demonstrated in other populations known to have high susceptibility to Type 2 diabetes. Even in youth, elevated fasting and 2-h insulin concentration is predictive of subsequent deterioration in glucose tolerance.     

Prevalence of Diabetes Mellitus in an Elderly Finnish Population

The prevalence of diabetes mellitus was investigated in a northern Finnish community population aged 70 years or over. Of the eligible 483 persons, 78.5% (n = 379) took part in the study. The presence of diabetes mellitus was assessed by questions about the participants' previously diagnosed diabetes and 2 h oral glucose tolerance tests, which were performed according to the current WHO criteria. Only the participants who were on oral hypoglycaemic drugs or insulin treatment were excluded from the 2 h oral glucose tolerance tests. In the total population the prevalence of Type 2 diabetes was 22.0% among men and 28.2% among women; the difference between sexes was not significant (women's risk ratio (RR) 1.3, 95% confidence interval (CI) 0.9-1.9). Among those aged 80 years or over the risk ratio for women was 11.3 compared with men (95% CI 1.6–79.5). Among men the prevalence was higher in the age group 70–79 years compared with those aged 80 years or over (RR 8.1, 95% CI 1.2–57.1). By contrast, among women, diabetes was less common among those aged 70–79 years compared with those aged 80 years or over (RR 0.6, 95% CI 0.4-1.0). The proportion of undiagnosed diabetes was clearly over one-third among men and just over one-third among women. Of men, 31.9% suffered from impaired glucose tolerance; the corresponding figure for women was 35.3%. The comparatively high proportion of undiagnosed diabetes and impaired glucose tolerance among elderly people lends support to the more frequent use of the 2 h glucose tolerance test in clinical practice.     

Antihypertensive drugs as predictors of type 2 diabetes among subjects with impaired glucose tolerance

Aims: to examine the incidence rate of progression to Type 2 diabetes and baseline prognostic risk factors, focusing on hypertension and antihypertensive medication, in a cohort (n=207) with impaired glucose tolerance (IGT). Methods: after 2 and 4.6 (1.9–6.4) years new cases of diabetes were diagnosed by the oral glucose tolerance test (OGTT). Hypertension (BP 160/95 or antihypertensive medication) was included in multiple regression analyses to assess the effect of risk factors on the development of diabetes. Results: diabetes developed in 32 subjects (19%), an incidence of 41/1000 (95% CI 28–57/1000) person-years. In univariate analyses, progression to diabetes was associated with a high (>9.0 mmol/l) 2-h OGTT value (P=0.008), a high fasting insulin (>12.0 mU/l) level (P=0.000), a high triglyceride (≥1.3 mmol/l) level (P=0.028), a high BMI (≥28.0 kg/m²) (P=0.013) and hypertension (P=0.003). The risk for the development of diabetes was not increased in hypertensive subjects without antihypertensive medication compared with normotensive subjects (OR 0.8, 95% CI 0.3–2.6). However, it was increased in subjects with on medication, especially diuretics alone or in combination with other drugs. Hypertensive subjects on diuretics had higher levels of fasting insulin and triglycerides and higher BMIs at baseline than normotensive subjects. After adjustment for 2-h OGTT, fasting insulin, triglycerides and BMI, the OR for diabetes was 7.7 (95% CI 2.1–28.2) in hypertensive subjects using diuretics alone or in combination with other drugs and 2.6 (95% CI 1.0–6.7) in those using other drugs compared with normotensive subjects. The OR of diabetes corresponding to a one-unit increase in the 2-h OGTT concentration was 2.5 (95% CI 1.6–4.0) in the whole cohort. Conclusions: the rate of progression from IGT to Type 2 diabetes in this population was similar to that seen in other studies among Caucasian populations. The use of antihypertensive medication, especially diuretics, and a high 2-h OGTT level were significant predictors of subsequent deterioration to diabetes.     

Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women

OBJECTIVES: The association between coffee consumption, type 2 diabetes and impaired glucose tolerance was examined. In addition, indicators of insulin sensitivity and beta-cell function according to homeostasis model assessment were studied in relation to coffee consumption. DESIGN: Population-based cross-sectional study. SETTING AND SUBJECTS: The study comprised 7949 healthy Swedish subjects aged 35-56 years residing within five municipalities of Stockholm. An oral glucose tolerance test identified 55 men and 52 women with previously undiagnosed type 2 diabetes and 172 men and 167 women with impaired glucose tolerance. Information about coffee consumption and other factors was obtained by questionnaire. RESULTS: The relative risks (adjusted for potential confounders) of type 2 diabetes and impaired glucose tolerance when drinking >/=5 cups of coffee per day compared with /=5 cups day(-1)) was inversely associated with insulin resistance. In addition, in those with type 2 diabetes and in women (not in men) with impaired glucose tolerance high coffee consumption was inversely associated with low beta-cell function. In women, but not obviously in men, with normal glucose tolerance, coffee consumption was associated with a reduced risk of insulin resistance. CONCLUSIONS: The results of this study indicated that high consumers of coffee have a reduced risk of type 2 diabetes and impaired glucose tolerance. The beneficial effects may involve both improved insulin sensitivity and enhanced insulin response.     

Poor physical fitness,and impaired early insulin response but late hyperinsulinaemia,as predictors of NIDDM in middle-aged Swedish men

Summary In a prospective population-based study of middle-aged Caucasian men, performed in Malmö, Sweden, specifically designed to evaluate physical fitness, early and late insulin response as predictors of non-insulin-dependent diabetes mellitus (NIDDM), 4,637 non-diabetic men underwent oral glucose tolerance tests at the ages of 48 and 54 years. At the baseline examination, physical fitness was measured in terms of lung vital capacity and oxygen uptake during ergometry; early insulin response in terms of the 40-min insulin increment during an oral glucose tolerance test (a correlate of acute insulin response to an intravenous glucose tolerance test), and late insulin response were measured in terms of the 2-h insulin value during the oral glucose tolerance test (a correlate of glucose disposal during euglycaemic clamp testing). Of the subjects studied 116 developed NIDDM (0.4% annually), and when compared with non-diabetic men at baseline, they were found to have an 11% higher mean body mass index (p<0.001), a higher frequency of family history of diabetes (31 vs 18%, p<0.001), 16% lower mean physical activity index (p<0.05), 16% lower mean estimated maximal oxygen uptake (p<0.001), 10% lower mean vital capacity (p<0.001), 26% lower 40-min to total insulin response ratio (p<0.001), and a 2.7 times higher mean 2-h insulin value during an oral glucose tolerance test (p<0.001). Regression analysis (using Cox's proportional hazards model) showed both low vital capacity, and impaired early insulin response but late hyperinsulinaemia to be independent predictors of NIDDM, in addition to body mass index and fasting blood glucose level (p=0.05–0.0001). Among subjects with impaired glucose tolerance at baseline (44 of 278 developed NIDDM), fasting glucose level alone predicted diabetes in this model. The findings suggest that in this age group in a Caucasian population, not only does insulin resistance precede glucose intolerance and NIDDM, but also loss of early insulin response indicating impaired beta-cell function to be an early feature of the process culminating in diabetes. As both physical fitness [which correlates inversely with late insulin response (r=–0.42, p<0.0001)], and the level of physical activity were shown to correlate with diabetes development in this large series, measures to correct these adverse features should be included in future strategies for preventing NIDDM.Abbreviations OGTT Oral glucose tolerance test - NGT normal glucose tolerance - IGT impaired glucose tolerance - NIDDM non-insulin-dependent diabetes mellitus - BMI body mass index - IVGTT intravenous glucose tolerance test     

Relationship Between Myo-Inositol Supplementary and Gestational Diabetes Mellitus: A Meta-Analysis

To determine whether myo-inositol supplement will increase the action of endogenous insulin, which is mainly measured by markers of insulin resistance such as homeostasis model assessment of insulin resistance.PubMed, Cochrane Library, Embase, and web of science were comprehensively searched using “gestational diabetes mellitus” and “myo-inositol” to identify relevant studies. Both subject headings and free texts were adopted. The methodological quality of the included studies were assessed and pooled analyzed by the methods recommended by the Cochrane collaboration.A total of 5 trials containing 513 participants were included. There was a significant reduction in aspects of gestational diabetes incidence (risk ratio [RR], 0.29; 95% confidence interval (95% CI), 0.19–0.44), birth weight (mean difference [MD], −116.98; 95% CI, −208.87 to −25.09), fasting glucose oral glucose tolerance test (OGTT) (MD, −0.36; 95% CI, −0.51 to −0.21), 1-h glucose OGTT (MD, −0.63; 95% CI, −1.01 to −0.26), 2-h glucose OGTT (MD, −0.45; 95% CI, −0.75 to −0.16), and related complications (odds ratio [OR], 0.28; 95% CI 0.14–0.58).On the basis of current evidence, myo-inositol supplementation reduces the development of gestational diabetes mellitus (GDM), although this conclusion requires further evaluation in large-scale, multicenter, blinded randomized controlled trials.     

Development of diabetes in Japanese subjects with impaired glucose tolerance: A seven year follow-up study

Summary Five hundred and seven subjects with postprandial glycosuria underwent a 50 g oral glucose tolerance test in an epidemiological survey of diabetes mellitus carried out in 1964–1965 in the town of Osaka, Japan. The oral glucose tolerance test was repeated 7 years later in 207 (40.8%) of the subjects. The results of the initial and the follow-up test were classified into three categories according to the new WHO criteria: normal, impaired glucose tolerance and diabetes. Most of the diabetic subjects (84.8%) remained unchanged between the initial and follow-up test. Of the subjects with impaired glucose tolerance at the time of the initial test, 38.5% showed diabetes in the follow-up test, while another 38.5% returned to normal. On the other hand, 13.5% of the normal subjects in the initial test developed impaired glucose tolerance or diabetes in the follow-up test. The rate of worsening to diabetes was related closely to the 2-h blood glucose value at the initial test. In addition, the rate of worsening was higher in males and obese subjects than in females and non-obese subjects. A multiple logistic analysis indicated that the fasting and 2-h glucose values were significantly predictive of worsening to diabetes.     

Glucose tolerance and cardiovascular risk in young adult African Americans

BACKGROUND: Patients with type 2 diabetes have higher rates of cardiovascular events. Among African Americans, there is a higher prevalence of both cardiovascular disease and type 2 diabetes. Few studies have examined longitudinally the change in glucose tolerance in younger adult African Americans. METHODS: To examine the longitudinal relationship of glucose tolerance with other cardiovascular risk factors, 30 African American men and women aged 20 to 43 years were examined twice at an interval of 4 to 5 years. Cardiovascular risk factors, glucose tolerance, and insulin sensitivity (determined from euglycemic hyperinsulinemic clamp procedure) were assessed at each examination. Known diabetics were excluded from initial enrollment. The relationship of glucose tolerance status (normal, impaired, or diabetic glucose tolerance) to body mass index, blood pressure, cholesterol, and insulin sensitivity were further investigated. RESULTS: Initial oral glucose tolerance test identified 24 of 130 (18.5%) subjects with impaired glucose tolerance and 2 of 130 (1.5%) subjects with diabetes. Of the remaining 104 subjects with normal glucose tolerance, subsequent 5-year examination detected 31 (29.8%) with impaired glucose tolerance and 5 (4.8%) with diabetes. Those who later developed diabetes had higher mean systolic blood pressure (133 versus 121, P = 0.037) at exam 1. By exam 2, those with abnormal glucose tolerance had worse cardiovascular risk profiles and increased insulin resistance (P < 0.001). CONCLUSION: Conversion to abnormal glucose tolerance is relatively frequent in young adult African Americans. Deterioration in glucose tolerance may be preceded by higher systolic blood pressure and is accompanied by worsening of other cardiovascular risk factors and insulin resistance.     

Loss of the First Phase Insulin Response to Intravenous Glucose in Subjects with Persistent Impaired Glucose Tolerance

Loss of the first phase insulin response to intravenous glucose is one of the earliest detectable defects of beta cell dysfunction in Type 2 diabetes mellitus. Impaired glucose tolerance (IGT) is considered a prediabetic condition, therefore loss of first phase insulin secretion in subjects with IGT would suggest beta cell dysfunction as an early lesion in the development of Type 2 diabetes. Three groups of subjects were studied, 7 subjects with persistent IGT (classified as having IGT at two 75 g oral glucose tolerance tests (OGTT) done 6 months apart), 6 subjects with transient IGT (IGT at the first OGTT, but normal glucose tolerance at a repeat OGTT 6 months later), and 7 normal controls. First phase insulin secretion was studied using an intravenous glucose tolerance test with arterialized blood sampling. Fasting, 3, 4 and 5 min samples were assayed for glucose and insulin (specific two-site immunoradiometric assay). The fasting insulin was similar in all three groups, however the 3 min insulin response was significantly lower in those with persistent impaired glucose tolerance (p < 0.02). Thus subjects with persistent impaired glucose tolerance demonstrated loss of the first phase insulin response as an early indicator of beta cell dysfunction while subjects with transient IGT had a normal insulin response to intravenous glucose. During the OGTT, the 30 min glucose was not significantly different (p = 0.1) but the 30 min insulin to glucose ratio was significantly lower in subjects with persistent IGT (p < 0.03). In the whole group the 30 min insulin to glucose ratio during the OGTT showed a significant correlation with the peak insulin response during the IVGTT (r = 0.76, p < 0.001). This study suggests that beta cell dysfunction with impaired early insulin release is present before the development of Type 2 diabetes.     

Misclassification of diabetic subjects may account for the increased vascular risk of impaired glucose tolerance: the Islington Diabetes Survey.

We have studied the associations of macrovascular disease and hypertension with impaired glucose tolerance in a recall sample of 223 subjects selected from a population aged greater than or equal to 40 years who had been screened for diabetes using two separate glucose tolerance tests. Blood pressure was higher in subjects with diabetes, but not in those with impaired glucose tolerance, than in normals. Coronary heart disease, based on ECG criteria and history, was more frequent both in subjects with impaired glucose tolerance (odds ratio 1.94, 95% CI 1.02-3.69) and those with diabetes (odds ratio 3.88, 95% CI 1.33-11.97) than in normals, but the excess in the impaired glucose tolerance group was reduced, and was no longer significant, when adjusted for other variables (odds ratio 1.29, 95% CI 0.62-2.66). Peripheral vascular disease was more frequent in subjects with diabetes, but not in those with impaired glucose tolerance. When the subjects with impaired glucose tolerance on a single test were reclassified according to the results of a separate glucose tolerance test, the prevalence of coronary heart disease increased significantly with increasing degrees of glucose intolerance. Subjects with impaired glucose tolerance on both tests had an adjusted odds ratio of coronary heart disease of 0.90 (95% CI 0.42-1.94) compared with normal subjects. The excess of macrovascular disease in subjects with impaired glucose tolerance may result, at least in part, from the admixture of 'false negative diabetics' in that class.     

Relationship between glucose tolerance,insulin secretion,and insulin action in non-obese individuals with varying degrees of glucose tolerance

Summary Plasma glucose and insulin concentration following a 75 g oral glucose challenge and glucose uptake during a hyperinsulinaemic glucose clamp study were determined in 50 non-obese individuals. The study population was divided into five groups on the basis of their glucose tolerance: normal, impaired glucose tolerance, Type 2 (non-insulin-dependent) diabetes mellitus with fasting plasma glucose of less than 8 mmol/l, between 8–15 mmol/l, and more than 15 mmol/l. The plasma insulin response was significantly greater (p<0.001) than normal in those with either impaired glucose tolerance or Type 2 diabetes and a fasting plasma glucose concentration less than 8 mmol/l. In contrast, the plasma insulin response was similar to normal in the other two groups of patients with Type 2 diabetes, i.e. fasting plasma glucose concentration 8–15 mmol/l or greater than 15 mmol/l. Glucose uptake rates were significantly lower (p<0.001) than normal in subjects with impaired glucose tolerance and all three groups of patients with Type 2 diabetes. Although glucose uptake rates during the glucose clamp studies were relatively similar in all four groups of glucose intolerant subjects, the values were significantly lower in those patients with Type 2 diabetes who had a fasting plasma glucose concentration greater than 8 mmol/l (p<0.01), These data indicate that a significant degree of insulin resistance exists in patients with impaired glucose tolerance or Type 2 diabetes, relatively independent of fasting plasma glucose concentration. Indeed, glucose uptake during glucose clamp studies fell 8-fold over a range in fasting plasma glucose concentration of from 4.5 to 6.5 mmol/l. In contrast, the plasma insulin response increased over the same range of fasting plasma glucose concentrations. The fact that this defect in insulin action can be seen in patients who are hyperinsulinaemic, not hypoinsulinaemic, and only modestly hyperglycaemic, is consistent with the hypothesis that resistance to insulin-stimulate glucose uptake is a basic characteristic of patients with impaired glucose tolerance or Type 2 diabetes.     

Low prevalence of islet autoimmunity in adult diabetes and low predictive value of islet autoantibodies in the general adult population of northern Italy

Aims/hypothesis. To assess the prevalence of islet autoimmunity in adult-onset diabetes mellitus and the predictive value of islet autoantibodies in the general adult population of northern Italy. Methods. A sample of 2076 people aged 40 years or more participating in the population-based Cremona Study and classified in 1990 as having diabetes mellitus, impaired and normal glucose tolerance according to WHO criteria after an oral glucose tolerance test, were tested for antibodies to glutamic acid decarboxylase and IA-2. Results. Increased concentrations of glutamic acid decarboxylase antibodies were found in 4 (2.8 %) of 143 participants with known diabetes and none of 50 with previously unknown diabetes, 1 (0.65 %) of 153 with impaired and 18 (1.0 %) of 1718 with normal glucose tolerance. The increased prevalence of these antibodies in subjects with known diabetes was not statistically significant. Protein tyrosine phosphatase IA-2-antibodies were found in only four subjects, two of whom also had glutamic acid decarboxylase antibodies, all with normal glucose tolerance. After 8 years of follow-up, none of 21 non-diabetic subjects with either glutamic acid decarboxylase or IA-2-antibodies had developed diabetes and only a slight deterioration from normal to impaired fasting glucose was observed in 3 of 15 subjects with previous normal glucose tolerance. Conclusion/interpretation. This study has shown that in northern Italy the prevalence of adult autoimmune diabetes in the general adult population is 0.19 % (95 % CI 0.05–0.5); that autoimmune diabetes represents only a minority of all cases of adult diabetes; and that islet autoantibodies are not a high-risk factor for diabetes development in adults with normal glucose tolerance over 8 years of follow-up. [Diabetologia (1999) 42: 840–844] Received: 29 December 1998 and in revised form: 9 March 1999