GH-binding protein in obese men with varying glucose tolerance: relationship to body fat distribution, insulin secretion and the GH-IGF-I axis.
(1/1659)
Bioelectrical impedance for measurement of total body fat and computed tomography for visceral and subcutaneous fat at umbilicus levels were performed in 34 obese and 10 lean men. Insulin secretion in response to an oral glucose tolerance test (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP) and IGF-I were measured. Obese subjects were divided into three groups according to the OGTT. The obese type II diabetes mellitus group had the highest GHBP levels and the most visceral fat. GHBP levels were most strongly correlated with the ratio of visceral fat area to body weight (VWR) above any other parameters (r = 0.725, P<0.001). The insulin and free fatty acid (FFA) areas under curves (AUC) during the OGTT, and the IGF-I level, were also positively correlated with GHBP levels (r = 0.474, P<0.005; r = 0.572, P<0.005; r = 0.453. P<0.005). GH-AUC to the L-dopa stimulation test was negatively correlated with GHBP levels (r = -0.432. P<0.005). Stepwise multiple linear regression analysis showed that VWR, FFA-AUC and insulin-AUC significantly contributed to the variability of GHBP (r2 = 0.58). In conclusion, we demonstrated that: (i) visceral fat amount mainly determined GHBP levels in obese men with varying glucose tolerance: (ii) hyperglycemia per se did not influence the GHBP level, whereas insulin and FFA could play a role in regulation of GHBP: and (iii) although GH was not the main regulator of GHBP, the unchanged IGF-I level despite GH hyposecretion suggests that increased GHBP levels reflect GH hypersensitivity in order to compensate for decreased GH secretion in obesity. (+info)
The role of apolipoprotein E and glucose intolerance in gallstone disease in middle aged subjects.
(2/1659)
BACKGROUND: The polymorphism of apolipoprotein E has been suggested to be associated with the cholesterol content of gallstones, the crystallisation rate of gall bladder bile, and the prevalence of gallstone disease (GSD). AIMS: To investigate whether apolipoprotein E polymorphism modulates the susceptibility to GSD at the population level and to study the possible associations between impaired glucose tolerance, diabetes, and GSD. METHODS: Apolipoprotein E phenotypes were determined in a middle aged cohort of 261 randomly selected hypertensive men, 259 control men, 257 hypertensive women, and 267 control women. All subjects without a documented history of diabetes were submitted to a two hour oral glucose tolerance test (OGTT). GSD was verified by ultrasonography. RESULTS: In women with apolipoprotein E2 (phenotypes E2/2, 2/3, and 2/4) compared with women without E2 (E3/3, 4/3, and 4/4), the odds ratio for GSD was 0. 28 (95% confidence interval 0.08-0.92). There was no protective effect in men. The relative risk for GSD was 1.2 (0.8-1.7) for hypertensive women and 1.8 (1.0-2.7) for hypertensive men. In a stepwise multiple logistic regression model, E2 protected against GSD in women, whereas two hour blood glucose in the OGTT, serum insulin, and plasma triglycerides were risk factors. Elevated blood glucose during the OGTT was also a significant risk factor for GSD in men. CONCLUSIONS: The data suggest that apolipoprotein E2 is a genetic factor providing protection against GSD in women. In contrast, impaired glucose tolerance and frank diabetes are associated with the risk of GSD. (+info)
Exclusion of insulin receptor substrate 2 (IRS-2) as a major locus for early-onset autosomal dominant type 2 diabetes.
(3/1659)
We investigated whether variability at the insulin receptor substrate (IRS)-2 locus plays a role in the etiology of early-onset autosomal dominant type 2 diabetes. By means of radiation hybrid mapping, we placed the human IRS-2 gene on 13q at 8.6 cRays from SHGC-37358. Linkage between diabetes and two polymorphic markers located in this region (D13S285 and D13S1295) was then evaluated in 29 families with early-onset autosomal dominant type 2 diabetes. Included were 220 individuals with diabetes, impaired glucose tolerance, or gestational diabetes (mean age at diabetes diagnosis 36 +/- 17 years) and 146 nondiabetic subjects. Overall, strongly negative logarithm of odds (LOD) scores for linkage with diabetes were obtained by multipoint parametric analysis (LOD score -45.4 at D13S285 and -40.9 at D13S1295). No significant evidence of linkage was obtained under the hypothesis of heterogeneity or by nonparametric methods. Fourteen pedigrees for which linkage could not be excluded (LOD score > -2.0) were screened for mutations in the IRS-2 coding region by dideoxy fingerprinting. However, no mutations segregating with diabetes could be detected in these families. These data indicate that IRS-2 is not a major gene for early-onset autosomal dominant type 2 diabetes, although a role of mutations in the promoter region cannot be excluded at this time. (+info)
Impaired fasting glucose or impaired glucose tolerance. What best predicts future diabetes in Mauritius?
(4/1659)
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. (+info)
Prevalence of undiagnosed diabetes and abnormalities of carbohydrate metabolism in a U.S. Army population.
(5/1659)
OBJECTIVE: The Third National Health and Nutrition Examination Survey (NHANES III) reported that 4.3-6.3% of adult Americans have undiagnosed diabetes. 15.6% have impaired glucose tolerance, and 10.1% have impaired fasting glucose. By design, NHANES III excluded people in the U.S. military. The purpose of this study was to determine the prevalence of undiagnosed diabetes, impaired glucose tolerance, and impaired fasting glucose among U.S. Army soldiers. RESEARCH DESIGN AND METHODS: A 2-h, 75-g oral glucose tolerance test was performed on a prospective, consecutive sample of 625 asymptomatic soldiers presenting to a U.S. Army medical clinic for physical examinations. Age of subjects was 32 +/- 9 years (mean +/- SD), and 81.0% of subjects were male. BMI was 26.2 +/- 3.7 kg/m2. Race/ethnicity categories included Caucasian (54.4%), African-American (24.4%), Hispanic (17.4%), and other (3.7%). A family history of diabetes was reported by 25.4% of the subjects, and the number of exercise sessions per week was 4.0 +/- 1.5. RESULTS: The prevalence of undiagnosed diabetes was 3 of 625 (0.5%) (95% CI, 0.1-1.4): impaired glucose tolerance, 11 of 598 (1.8%) (0.9-3.3); and impaired fasting glucose 6 of 585 (1.0%) (0.4-2.2). CONCLUSIONS: In this low-diabetes risk U.S. Army population, the prevalence of undiagnosed diabetes, impaired glucose tolerance, and impaired fasting glucose were 0.5, 1.8, and 1.0%, respectively. The prevalence rates found in this study are approximately one-tenth of those found in NHANES III. (+info)
Standardized comparison of glucose intolerance in west African-origin populations of rural and urban Cameroon, Jamaica, and Caribbean migrants to Britain.
(6/1659)
OBJECTIVE: To compare the prevalence of glucose intolerance in genetically similar African-origin populations within Cameroon and from Jamaica and Britain. RESEARCH DESIGN AND METHODS: Subjects studied were from rural and urban Cameroon or from Jamaica, or were Caribbean migrants, mainly Jamaican, living in Manchester, England. Sampling bases included a local census of adults aged 25-74 years in Cameroon, districts statistically representative in Jamaica, and population registers in Manchester. African-Caribbean ethnicity required three grandparents of this ethnicity. Diabetes was defined by the World Health Organization (WHO) 1985 criteria using a 75-g oral glucose tolerance test (2-h > or = 11.1 mmol/l or hypoglycemic treatment) and by the new American Diabetes Association criteria (fasting glucose > or = 7.0 mmol/l or hypoglycemic treatment). RESULTS: For men, mean BMIs were greatest in urban Cameroon and Manchester (25-27 kg/m2); in women, these were similarly high in urban Cameroon and Jamaica and highest in Manchester (27-28 kg/m2). The age-standardized diabetes prevalence using WHO criteria was 0.8% in rural Cameroon, 2.0% in urban Cameroon, 8.5% in Jamaica, and 14.6% in Manchester, with no difference between sexes (men: 1.1%, 1.0%, 6.5%, 15.3%, women: 0.5%, 2.8%, 10.6%, 14.0%), all tests for trend P < 0.001. Impaired glucose tolerance was more frequent in Jamaica. CONCLUSIONS: The transition in glucose intolerance from Cameroon to Jamaica and Britain suggests that environment determines diabetes prevalence in these populations of similar genetic origin. (+info)
Altered beta-cell characteristics in impaired glucose tolerant carriers of a GAA trinucleotide repeat polymorphism in the frataxin gene.
(7/1659)
Friedreich's ataxia is associated with GAA trinucleotide repeat expansions in the frataxin gene. In the general population, these trinucleotide expansions are variable in length, and three types of expansions are seen: short, intermediate, and long repeats. Friedreich's ataxia patients are generally homozygous for the long repeats and exhibit diabetes as pronounced comorbidity. Ristow et al. recently reported an association between the intermediate-length normal allele in the frataxin gene and type 2 diabetes. We have investigated in 94 subjects with impaired glucose tolerance (IGT) as to whether the length of the GAA trinucleotide repeat polymorphism in the frataxin gene associates with parameters reflecting beta-cell function. A hyperglycemic clamp at 10 mmol/l glucose for 3 h was used to quantitate beta-cell characteristics. Carriers of one or two intermediate repeat alleles (n = 32) had a 50% higher median first- phase insulin response to glucose than the noncarriers. Furthermore, they needed less time to reach peak insulin. An analysis of the distribution of the various repeat lengths in elderly type 2 diabetic (n = 179) and control subjects (n = 183), with the same age and ethnic background, did not provide evidence for an association of the intermediate-length repeat allele with type 2 diabetes in Dutch Caucasians. (+info)
High incidence of glucose intolerance in Vogt-Koyanagi-Harada disease.
(8/1659)
AIMS: To evaluate glucose tolerance of patients with Vogt-Koyanagi-Harada (VKH) disease before systemic corticosteroid therapy, and to assess changes brought on by treatment. METHODS: 20 VKH patients with acute bilateral panuveitis were studied. 20 healthy adults and 11 Behcet's disease patients with active uveoretinitis served as controls. A 75 g oral glucose tolerance test (OGTT) was given in the acute stage of ocular inflammation before systemic corticosteroid therapy. The OGTT was repeated in the convalescent stage of VKH disease in the patients with glucose intolerance before treatment. Insulin response was examined at the same time as the OGTT when possible. RESULTS: 55% of VKH patients (11/20) showed glucose intolerance but no apparent insulin secretion deficiency was detected. Four of seven patients in the convalescent stage showed improvement of glucose tolerance. None of the normal controls or disease controls showed glucose intolerance. CONCLUSION: A high incidence of glucose intolerance was found in the acute stage of VKH disease. However, glucose intolerance improved in most cases after systemic corticosteroid therapy. It is possible that glucose intolerance seen in VKH patients may be related to the autoimmune inflammatory process of this disease. (+info)