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Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.

ABSTRACT: OBJECTIVE:Metabolic syndrome is associated with insulin resistance and increased future risk of type 2 diabetes. This study investigates the relationship between insulin secretion, insulin resistance and individual metabolic syndrome components in subjects without a prior diagnosis of diabetes. RESEARCH DESIGN AND METHODS:We assessed insulin secretion during hyperglycemic clamps by infusing dextrose to maintain hyperglycemia (200mg/dL), followed by L-arginine administration. Studies in 98 individuals (mean age 45.3±1.2years, 56% female, 22% African-American, 49% with metabolic syndrome) were analyzed. We tested the association between the number of metabolic syndrome components and individual outcome variables using linear mixed-effects models to adjust for potential confounding effects of age, sex, and race. RESULTS:Insulin sensitivity index was reduced in the presence of 1 or more metabolic syndrome components. Insulin sensitivity was independently associated with age, waist circumference, male gender and decreased HDL cholesterol. The acute insulin response was greater with two or more metabolic syndrome components, and late glucose-stimulated and L-arginine-stimulated insulin responses exhibited a similar trend. In contrast, the disposition index, a measure of beta cell compensation for insulin resistance, was linearly lower with the number of metabolic syndrome components, and was negatively associated with age, Caucasian race, waist circumference, fasting glucose, and decreased HDL cholesterol. CONCLUSIONS:The insulin secretory response in metabolic syndrome is inadequate for the worsening insulin sensitivity, as demonstrated by a decline in disposition index. A dysfunctional insulin secretory response is evident in non-diabetic individuals and worsens with accumulation of metabolic syndrome components.

SUBMITTER: Shah SS

PROVIDER: S-EPMC4867079 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.

Shah Sapna S SS Ramirez Claudia E CE Powers Alvin C AC Yu Chang C Shibao Cyndya A CA Luther James M JM

Metabolism: clinical and experimental 20160226 6

<h4>Objective</h4>Metabolic syndrome is associated with insulin resistance and increased future risk of type 2 diabetes. This study investigates the relationship between insulin secretion, insulin resistance and individual metabolic syndrome components in subjects without a prior diagnosis of diabetes.<h4>Research design and methods</h4>We assessed insulin secretion during hyperglycemic clamps by infusing dextrose to maintain hyperglycemia (200mg/dL), followed by L-arginine administration. Studi ...[more]

PMID: 27173462

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Project description:Introduction Obesity and metabolic syndrome (MetS) have immediate and long-term consequences on adolescent health and well-being. Among the available treatments for MetS in adolescents, behavioral interventions such as increasing physical activity (PA) are preferred. This study aimed to investigate the association of PA and sitting time with MetS and a complete set of metabolic health parameters. Methods Data from the Pediatric Brazilian Metabolic Syndrome Study (BRAMS-P), a cross-sectional multicenter study conducted using a convenience sample of 448 Brazilian adolescents (10y–19y), were used. Sociodemographic and lifestyle information were collected using a standardized questionnaire. Daily PA and sitting time were estimated from the International PA Questionnaire. Anthropometric parameters, body composition, and blood pressure were measured by trained researchers. Blood lipids, uric acid, hepatic enzymes, creatinine, glycated hemoglobin, glucose, and insulin were measured in fasting blood samples, and the Homeostasis Model Assessment for Insulin Resistance was calculated. A subsample of 57 adolescents underwent the hyperglycemic clamp protocol. Results The odds for metabolic syndrome were higher among adolescents who spent >8h sitting (OR (95%CI)=2.11 (1.02 – 4.38)), but not in those classified as active (OR (95%CI)=0.98 (0.42 – 2.26)). Adolescents who spent more time sitting had higher BMI, waist circumference, sagittal abdominal diameter, neck circumference, percentage of body fat, and worse blood lipid profile. The insulin sensitivity index was moderately and positively correlated with moderate-to-high PA in minutes per day (rho=0.29; p=0.047). Conclusion Time spent sitting was associated with worse metabolic parameters and must be restricted in favor of adolescent health. Regular PA is associated with improved insulin sensitivity and may be encouraged not only in adolescents with obesity or metabolic disorders but also to prevent adverse metabolic outcomes in normal-weight adolescents.

Project description:Multiple studies suggest that hypoxia, together with inflammation, could be one of the phenomena involved in the onset and progression of obesity-related insulin resistance. In addition, dysfunction of adipose tissue in obese subjects with metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. The aim of the current study was to examine the neovascular properties of visceral adipose tissue-derived multipotent mesenchymal cells subjected to hypoxia (hypox-visASCs) from normal-weight subjects (Nw) and obese patients with metabolic syndrome (MS) and without metabolic syndrome (NonMS).This was a 2-year study to enroll subjects who underwent bariatric surgery or cholecystectomy. Eight patients who underwent either bariatric surgery or cholecystectomy (27 patients) participated in the study. Visceral adipose tissue samples from Nw, MS and NonMS subjects were processed by enzymatic digestion. VisASCs cultured under hypoxic conditions were characterized by tubule formation assay, ELISA, flow cytometry, migration rate, and qRT-PCR, and the effects of visASCs-conditioned medium on survival and endothelial cell tubule formation were evaluated.Hypox-visASCs from NonMS subjects showed a greater capacity for tubule formation than hypox-visASCs from Nw and MS subjects. The lower percentage of CD140b+/CD44+ and CD140b+/CD184+ cells observed in hypox-visASCs from NonMS subjects compared to MS subjects was accompanied not only by a lower migration rate from the chemotactic effects of stromal cell derived factor 1?, but also by lower levels of NOX5 mRNA expression. While the levels of monocyte chemoattractant protein 1 mRNA expressed by hypox-visASCs correlated positively with the body mass index and waist circumference of the subjects, the concentration of vascular endothelial growth factor present in hypox-visASC-conditioned culture medium decreased significantly with increasing plasma glucose. The survival rate and tubules formed by endothelial cells cultured in hypox-visASC-conditioned medium decreased significantly with increasing homeostasis model assessment to quantify insulin resistance.Our results suggest that hypox-visASCs from NonMS subjects could promote healthy adipose tissue expansion, while hypox-visASCs from MS subjects appear to contribute to the decreased angiogenic potential and increased inflammation underlying adipose tissue dysfunction in obesity. Our results emphasize the importance of taking into account not only the BMI but also the metabolic profile of the subjects during the implementation of ASCs-based therapy to promote neovascularization.

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Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.

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Hyperglycemic clamp-derived disposition index is negatively associated with metabolic syndrome severity in obese subjects.

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