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Insulin Sensitivity and ?-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents.

ABSTRACT: OBJECTIVE:To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). STUDY DESIGN:A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 ± 1.42 years; range 14.5-20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity index), insulin secretion (acute insulin response to glucose ), and the disposition index as primary outcome variables. These variables were compared over the 1 year of observation using linear mixed modeling. RESULTS:In the 1-year following surgery, body mass index fell by 38% from a mean of 61 ± 12.3 to 39 ± 8.0 kg/m(2) (P < .01). Over the year following surgery, fasting glucose and insulin values declined by 54% and 63%, respectively. Insulin sensitivity index increased 300% (P < .01), acute insulin response to glucose decreased 56% (P < .01), leading to a nearly 2-fold increase in the disposition index (P < .01). Consistent with improved ?-cell function, the proinsulin to C-peptide ratio decreased by 21% (P < .01). CONCLUSIONS:RYGB reduced body mass index and improved both insulin sensitivity and ?-cell function in severely obese teens and young adults. These findings demonstrate that RYGB is associated with marked metabolic improvements in obese young people even as significant obesity persists. TRIAL REGISTRATION:ClinicalTrials.gov: NCT00360373.

SUBMITTER: Inge TH

PROVIDER: S-EPMC4843108 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Insulin Sensitivity and β-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents.

Inge Thomas H TH Prigeon Ronald L RL Elder Deborah A DA Jenkins Todd M TM Cohen Robert M RM Xanthakos Stavra A SA Benoit Stephen C SC Dolan Lawrence M LM Daniels Stephen R SR D'Alessio David A DA

The Journal of pediatrics 20150909 5

<h4>Objective</h4>To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB).<h4>Study design</h4>A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 ± 1.42 years; range 14.5-20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity ...[more]

PMID: 26363548

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Project description:BACKGROUND/OBJECTIVES:Impaired insulin-mediated glucose partitioning is an intrinsic metabolic defect in skeletal muscle from severely obese humans (BMI???40?kg/m2). Roux-en-Y gastric bypass (RYGB) surgery has been shown to improve glucose metabolism in severely obese humans. The purpose of the study was to determine the effects of RYGB surgery on glucose partitioning, mitochondrial network morphology, and the markers of mitochondrial dynamics skeletal muscle from severely obese humans. SUBJECT/METHODS:Human skeletal muscle cells were isolated from muscle biopsies obtained from RYGB patients (BMI?=?48.0?±?2.1, n?=?7) prior to, 1 month and 7 months following surgery and lean control subjects (BMI?=?22.4?±?1.1, n?=?7). Complete glucose oxidation, non-oxidized glycolysis rates, mitochondrial respiratory capacity, mitochondrial network morphology, and the regulatory proteins of mitochondrial dynamics were determined in differentiated human myotubes. RESULTS:Myotubes derived from severely obese humans exhibited enhanced glucose oxidation (13.5%; 95% CI [7.6, 19.4], P?=?0.043) and reduced non-oxidized glycolysis (-1.3%; 95% CI [-11.1, 8.6]) in response to insulin stimulation at 7 months after RYGB when compared with the presurgery state (-0.6%; 95% CI [-5.2, 4.0] and 19.5%; 95% CI [4.0, 35.0], P?=?0.006), and were not different from the lean controls (16.7%; 95% CI [11.8, 21.5] and 1.9%; 95% CI [-1.6, 5.4], respectively). Further, the number of fragmented mitochondria and Drp1(Ser616) phosphorylation were trended to reduce/reduced (0.0104, 95% CI [0.0085, 0.0126], P?=?0.091 and 0.0085, 95% CI [0.0068, 0.0102], P?=?0.05) in myotubes derived from severely obese humans at 7 months after RYGB surgery in comparison with the presurgery state. Finally, Drp1(Ser616) phosphorylation was negatively correlated with insulin-stimulated glucose oxidation (r?=?-0.49, P?=?0.037). CONCLUSION/INTERPRETATION:These data indicate that an intrinsic metabolic defect of glucose partitioning in skeletal muscle from severely obese humans is restored by RYGB surgery. The restoration of glucose partitioning may be regulated through reduced mitochondrial fission protein Drp1 phosphorylation.

Project description:BackgroundThyrotropin (TSH) levels display a positive association with body mass index (BMI), and the prevalence of isolated hyperthyrotropinemia is higher in obese adolescents compared to their normal weight controls. However, the metabolic significance of the higher TSH in obese adolescents is less clear. The objective of this study was to determine the relationship between TSH concentrations and insulin sensitivity, lipids, and adipokines in euthyroid, non-diabetic, obese adolescents.MethodsThirty-six euthyroid, non-diabetic, obese adolescents between the ages of 12 and 18 years underwent a 75 g oral glucose tolerance test. Insulin sensitivity (Si) and pancreatic β-cell function as assessed by disposition index (DI) were measured using the oral glucose minimal model approach. Cholesterol (total, low-density lipoprotein [LDL-C], and high-density lipoprotein [HDL-C]), triglycerides (TG), interleukin-6 (IL-6), total and high molecular weight (HMW) adiponectin, and retinol binding protein-4 (RBP4) were also determined. Associations between measures of thyroid function and Si, DI, lipids, and adipokines were computed using Pearson's correlation coefficient and multiple regression analysis.ResultsThe mean age of the subjects was 14.3±1.88 years, and the mean BMI was 32.5±4.65 kg/m2; 97% were non-Hispanic white and 47% were male. The mean TSH was 2.7±1.2 mIU/L. Increasing serum TSH was correlated with decreasing Si (log Si) in the entire cohort (p=0.03), but this relationship persisted only in males (p=0.02). The correlation between TSH and Si in males remained significant after adjusting for BMI (p=0.02). There was no correlation between TSH and pancreatic β-cell function as assessed by DI (p=0.48). TSH correlated positively with LDL-C (p=0.04) and IL-6 (p=0.03), but these associations vanished or weakened after adjusting for BMI (LDL-C p-value=0.44; IL-6 p-value=0.07).ConclusionsThis study suggests a sex-specific association between TSH and insulin sensitivity in euthyroid, non-diabetic, obese adolescent males. Prospective studies are warranted to explore further this sexual dimorphism in the relationship between thyroid function and insulin sensitivity and to determine if obese adolescents with insulin resistance receiving thyroid supplements for hypothyroidism would benefit from targeting TSH levels in the lower half of normal range.

Dataset Information

Insulin Sensitivity and ?-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents.

Publications

Insulin Sensitivity and β-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents.

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