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OBJECTIVE - South Asians have a higher prevalence of type 2 diabetes compared with other race/ethnic groups. Body composition is associated with the risk for type 2 diabetes. Differences in body composition between South Asians and other race/ethnic groups are one hypothesized mechanism to explain the disproportionate prevalence of type 2 diabetes in this population.
RESEARCH DESIGN AND METHODS - This study used data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and the Multi-Ethnic Study of Atherosclerosis (MESA) cohorts to determine whether body composition mediated the elevated prevalence of impaired fasting glucose and type 2 diabetes in South Asians. Participants ( = 2,615) with complete body composition data were included. Ordinal logistic regression models were calculated to determine the odds for glycemic impairment in South Asians compared with the MESA cohort.
RESULTS - In multivariate models, South Asians had a significantly higher prevalence of glycemic impairment and type 2 diabetes compared with all four race/ethnic groups included in the MESA ( < 0.001 for all). In unadjusted and multivariate adjusted models, South Asians had higher odds for impaired fasting glucose and type 2 diabetes compared with all other race/ethnic groups ( < 0.001 for all). The addition of body composition measures did not significantly mitigate this relationship.
CONCLUSIONS - We did not identify strong evidence that accounting for body composition explains differences in the risk for type 2 diabetes. Future prospective studies of the MESA and MASALA cohorts are needed to understand how adipose tissue impacts the risk for type 2 diabetes and how to best assess this risk.
© 2019 by the American Diabetes Association.
AIM - To evaluate the relationship of abdominal muscle lean tissue and adipose tissue volumes with prediabetes and diabetes.
RESEARCH DESIGN AND METHODS - We measured abdominal muscle composition in 3170 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent computed tomography (CT) at Year 25 of follow-up (ages, 43-55 years). Multinomial regression analysis was used to evaluate the associations of CT-measured intermuscular adipose tissue (IMAT), lean muscle tissue (lean) and visceral adipose tissue (VAT) volumes with diabetes at any point during the CARDIA study, newly detected prediabetes, prior history of prediabetes, and normal glucose tolerance. Models were adjusted for potential confounding factors: age, sex, race, height, smoking status, hypertension, hyperlipidaemia, cardiorespiratory fitness and study centre.
RESULTS - Higher IMAT, lean and VAT volumes were all separately associated with a higher prevalence of prediabetes and diabetes. Inclusion of VAT volume in models with both IMAT volume and lean volume attenuated the association of IMAT with both prediabetes and diabetes, but higher lean volume retained its association with prediabetes and diabetes. Individuals in the highest IMAT quartile, coupled with VAT in its lower three quartiles, had a higher prevalence of diabetes, but not of prediabetes, than those with both IMAT and VAT in their respective lower three quartiles. Adjusting for cardiorespiratory fitness did not substantially change the findings.
CONCLUSION - Higher IMAT volume was associated with a higher prevalence of diabetes even after adjustment for VAT volume. However, further study is warranted to understand the complicated relationship between abdominal muscle and adipose tissues.
© 2018 John Wiley & Sons Ltd.
The frequency of prediabetes is increasing as the prevalence of obesity rises worldwide. In prediabetes, hyperglycemia, insulin resistance, and inflammation and metabolic derangements associated with concomitant obesity cause endothelial vasodilator and fibrinolytic dysfunction, leading to increased risk of cardiovascular and renal disease. Importantly, the microvasculature affects insulin sensitivity by affecting the delivery of insulin and glucose to skeletal muscle; thus, endothelial dysfunction and extracellular matrix remodeling promote the progression from prediabetes to diabetes mellitus. Weight loss is the mainstay of treatment in prediabetes, but therapies that improved endothelial function and vasodilation may not only prevent cardiovascular disease but also slow progression to diabetes mellitus.
© 2018 American Heart Association, Inc.
OBJECTIVE - To determine whether the duration of diabetes and duration of prediabetes estimated during a 25-year period in early adulthood are each independently associated with coronary artery calcified plaque (CAC) and abnormalities in left ventricular structure and function later in life.
RESEARCH DESIGN AND METHODS - Participants were 3,628 white and black adults aged 18-30 years without diabetes or prediabetes at baseline (1985-1986) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Durations of diabetes and prediabetes were estimated based on their identification at examinations 7, 10, 15, 20, and 25 years later. CAC was identified by computed tomography at years 15, 20, and 25. Left ventricular structure and function were measured via echocardiogram at year 25.
RESULTS - Of the 3,628 individuals, 12.7% and 53.8% developed diabetes and prediabetes, respectively; average (SD) duration was 10.7 (10.7) years and 9.5 (5.4) years. After adjustment for sociodemographic characteristics and other cardiovascular risk factors, and mutual adjustment for each other, the hazard ratio for the presence of CAC was 1.15 (95% CI 1.06, 1.25) and 1.07 (1.01, 1.13) times higher for each 5-year-longer duration of diabetes and prediabetes, respectively. Diabetes and prediabetes duration were associated with worse subclinical systolic function (longitudinal strain [ < 0.001 for both]) and early diastolic relaxation (e' [ 0.004 and 0.002, respectively]). Duration of diabetes was also associated with a higher diastolic filling pressure (E-to-e' ratio [ 0.001]).
CONCLUSIONS - Durations of diabetes and prediabetes during adulthood are both independently associated with subclinical atherosclerosis and left ventricular systolic and diastolic dysfunction in middle age.
© 2018 by the American Diabetes Association.
CONTEXT - Sildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance.
OBJECTIVE - The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function.
DESIGN - This was a randomized, double-blind, placebo-controlled study.
SETTING - This trial was conducted at Vanderbilt Clinical Research Center.
PARTICIPANTS - Participants included overweight individuals with prediabetes.
INTERVENTIONS - Subjects were randomized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months. Subjects underwent a hyperglycemic clamp prior to and at the end of treatment.
MAIN OUTCOME MEASURES - The primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion.
RESULT - Twenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per μU/mL*100 (95% confidence interval, 0.01 to 3.67 mg/kg/min per μU/mL*100; P = .049), after adjusting for baseline insulin sensitivity index and body mass index. In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion (P > .30). Sildenafil decreased plasminogen activator inhibitor-1 (P = .01), without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 μg/mg Cr. This effect persisted 3 months after sildenafil discontinuation.
CONCLUSIONS - Three-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function.
OBJECTIVE - To determine the association between race, region and pre-diabetes.
METHOD - The study used 2003-2007 United States baseline data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study for this cross-sectional analysis. Participants in this study were 45years or older at recruitment. Logistic regression was used to assess whether race and region are associated with pre-diabetes independent of demographics, socioeconomic factors and risk factors.
RESULTS - Twenty-four percent of the study participants (n=19,889) had pre-diabetes. The odds ratio (95% confidence interval) for having pre-diabetes was 1.28 (1.19-1.36) for blacks relative to whites and 1.18 (1.10-1.26) for people living in the Stroke Belt region relative to the other parts of the United States. The odds of having pre-diabetes for Stroke Belt participants changed minimally after additional adjustment for race (OR=1.20; 1.13-1.28), age and sex (OR=1.24; 1.16-1.32), socioeconomic status (OR=1.22; 1.15-1.31) and risk factors (OR=1.26; 1.17-1.35). In the adjusted model, being black was independently associated with pre-diabetes (OR=1.19; 1.10-1.28).
CONCLUSION - The prevalence of pre-diabetes was higher for both blacks and whites living in the Stroke Belt relative to living outside the Stroke Belt, and the prevalence of pre-diabetes was higher for blacks independent of region.
Copyright © 2014 Elsevier Inc. All rights reserved.
We studied the change in the first-phase insulin response (FPIR) during the progression to type 1 diabetes (T1D). Seventy-four oral insulin trial progressors to T1D from the Diabetes Prevention Trial-Type 1 with at least one FPIR measurement after baseline and before diagnosis were studied. The FPIR was examined longitudinally in 26 progressors who had FPIR measurements during each of the 3 years before diagnosis. The association between the change from the baseline FPIR to the last FPIR and time to diagnosis was studied in the remainder (n = 48). The 74 progressors had lower baseline FPIR values than nonprogressors (n = 270), with adjustments made for age and BMI. In the longitudinal analysis of the 26 progressors, there was a greater decline in the FPIR from 1.5 to 0.5 years before diagnosis than from 2.5 to 1.5 years before diagnosis. This accelerated decline was also evident in a regression analysis of the 48 remaining progressors in whom the rate of decline became more marked with the approaching diagnosis. The patterns of decline were similar between the longitudinal and regression analyses. There is an acceleration of decline in the FPIR during the progression to T1D, which becomes especially marked between 1.5 and 0.5 years before diagnosis.
To identify distinct biological pathways of glucose metabolism, we conducted a systematic evaluation of biochemical changes after an oral glucose tolerance test (OGTT) in a community-based population. Metabolic profiling was performed on 377 nondiabetic Framingham Offspring cohort participants (mean age 57 years, 42% women, BMI 30 kg/m(2)) before and after OGTT. Changes in metabolite levels were evaluated with paired Student t tests, cluster-based analyses, and multivariable linear regression to examine differences associated with insulin resistance. Of 110 metabolites tested, 91 significantly changed with OGTT (P ≤ 0.0005 for all). Amino acids, β-hydroxybutyrate, and tricarboxylic acid cycle intermediates decreased after OGTT, and glycolysis products increased, consistent with physiological insulin actions. Other pathways affected by OGTT included decreases in serotonin derivatives, urea cycle metabolites, and B vitamins. We also observed an increase in conjugated, and a decrease in unconjugated, bile acids. Changes in β-hydroxybutyrate, isoleucine, lactate, and pyridoxate were blunted in those with insulin resistance. Our findings demonstrate changes in 91 metabolites representing distinct biological pathways that are perturbed in response to an OGTT. We also identify metabolite responses that distinguish individuals with and without insulin resistance. These findings suggest that unique metabolic phenotypes can be unmasked by OGTT in the prediabetic state.
OBJECTIVE - Nondiabetic subjects with a 1-h plasma glucose >or= 11.1 mmol/l during an oral glucose tolerance test (OGTT) drew our attention to their somewhat confusing status and relative frequency among Chinese patients. The aim of this study was to clarify the metabolic characteristics of these subjects.
DESIGN AND PATIENTS - A total of 2549 Chinese subjects were included in this study. Based on results of OGTT, these subjects were classified into three groups: normal glucose tolerance (NGT), impaired glucose regulation (IGR) and diabetes mellitus (DM). Then, according to the level of 1-h plasma glucose, the NGT and IGR groups were subclassified, respectively, as: NGT without 1-h hyperglycaemia (NGTN), NGT with hyperglycaemia at 1 h (NGT1H), IGR without 1-h hyperglycaemia (IGRN), and IGR with hyperglycaemia at 1 h (IGR1H).
RESULTS - After adjustments for age and gender, the insulinogenic index (IGI) of NGT1H and IGR1H was found to be lower than for those with NGTN and of IGRN, respectively (P < 0.05). No statistical differences, however, were found in oral glucose insulin sensitivity (OGIS) between either of the 1-h hyperglycaemic groups or of the corresponding NGTN or IGRN groups. Homeostasis model assessment for beta-cell function (HOMA-B) of NGT1H was lower than that of NGTN (P < 0.05), while IGRN and IGR1H showed no difference. No differences in homeostasis model assessment for insulin resistance (HOMA-IR) were found among NGTN, NGT1H, IGRN and IGR1H groups. The levels of triglycerides (TG) were not significantly different among NGT1H, IGRN and IGR1H, while TG in these groups were significantly higher than in NGTN (P < 0.05). LDL-C was significantly higher and HDL significantly lower in NGT1H than in all other groups (P < 0.05).The IGR group was also subclassified as: isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined glucose intolerance (CGI). The IGI of the NGT1H group was similar to the IGI that of combined glucose intolerance group but lower than those of IFG and IGT (P < 0.05).The OGIS of the NGT1H group was the highest among all groups (P < 0.05). HOMA-B of IGT and NGT1H were higher than that of IFG (P < 0.05). There was no difference among all groups in HOMA-IR. Plasma lipid levels were not significantly different between NGT1H and any other group.
CONCLUSIONS - Chinese NGT subjects with a 1-h plasma glucose >/= 11.1 mmol/l are characterized by metabolic abnormalities, which may be caused by the impairment of early insulin release rather than aggravated insulin resistance.