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Intraperitoneal fat and insulin resistance in obese adolescents.

ABSTRACT: Obesity is epidemic among adolescents in the United States. We sought to analyze the anthropometric measures of adiposity and fasting indices of insulin resistance, including insulin-like growth factor-binding protein-1 (IGFBP-1), and to provide a clinical estimate of intraperitoneal (IP) fat in obese adolescents (BMI > or =95th percentile), between ages 13 and 17 years. Subjects had baseline testing to determine eligibility for a subsequent randomized, placebo-controlled trial of metformin XR therapy. Anthropometry and dual-energy X-ray absorptiometry (DXA) were used to quantify total body fat while abdominal computed tomography (CT) was used to measure IP (CT-IP) and subcutaneous (CT-SQ) fat. Using anthropometry and fasting laboratory data, we constructed regression models for both CT-IP and CT-SQ. A total of 92 subjects, 33 males, were evaluated. Of the 92 subjects, 19 were black. Fasting insulin concentrations were highly associated with other measures of insulin resistance. Median percent body fat across all subjects, as measured by DXA, was 41%. Using CT measures, 67% of abdominal cross-sectional area was fat, 14% of which was IP fat. In multiple regression analysis, waist circumference (WC) and BMI, jointly and independently, were strongly associated with both CT-IP and CT-SQ fat. BMI and WC explained 62% of variance of CT-SQ fat, but only 26% of variance of CT-IP fat. Adding triglyceride:high-density lipoprotein (TG:HDL) ratio and IGFBP-1 (among nonblacks) to the regression model increased the explained variance for estimating CT-IP fat to 45%. When evaluating the metabolic morbidity of an obese adolescent, a model using fasting IGFBP-1, TG:HDL, BMI, and WC may be worthwhile as an estimate of IP fat.

SUBMITTER: Glaser Pediatric Research Network Obesity Study Group

PROVIDER: S-EPMC3507443 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Intraperitoneal fat and insulin resistance in obese adolescents.

Obesity (Silver Spring, Md.) 20090827 2

Obesity is epidemic among adolescents in the United States. We sought to analyze the anthropometric measures of adiposity and fasting indices of insulin resistance, including insulin-like growth factor-binding protein-1 (IGFBP-1), and to provide a clinical estimate of intraperitoneal (IP) fat in obese adolescents (BMI > or =95th percentile), between ages 13 and 17 years. Subjects had baseline testing to determine eligibility for a subsequent randomized, placebo-controlled trial of metformin XR t ...[more]

PMID: 19713950

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Project description:AIMS/HYPOTHESIS:A genetic risk score (GRS) consisting of 53 insulin resistance variants (GRS53) was recently demonstrated to associate with insulin resistance in adults. We speculated that the GRS53 might already associate with insulin resistance during childhood, and we therefore aimed to investigate this in populations of Danish children and adolescents. Furthermore, we aimed to address whether the GRS associates with components of the metabolic syndrome and altered body composition in children and adolescents. METHODS:We examined a total of 689 children and adolescents who were overweight or obese and 675 children and adolescents from a population-based study. Anthropometric data, dual-energy x-ray absorptiometry scans, BP, fasting plasma glucose, fasting serum insulin and fasting plasma lipid measurements were obtained, and HOMA-IR was calculated. The GRS53 was examined for association with metabolic traits in children by linear regressions using an additive genetic model. RESULTS:In overweight/obese children and adolescents, the GRS53 associated with higher HOMA-IR (β = 0.109 ± 0.050 (SE); p = 2.73 × 10-2), fasting plasma glucose (β = 0.010 ± 0.005 mmol/l; p = 2.51 × 10-2) and systolic BP SD score (β = 0.026 ± 0.012; p = 3.32 × 10-2) as well as lower HDL-cholesterol (β = -0.008 ± 0.003 mmol/l; p = 1.23 × 10-3), total fat-mass percentage (β = -0.143 ± 0.054%; p = 9.15 × 10-3) and fat-mass percentage in the legs (β = -0.197 ± 0.055%; p = 4.09 × 10-4). In the population-based sample of children, the GRS53 only associated with lower HDL-cholesterol concentrations (β = -0.007 ± 0.003 mmol/l; p = 1.79 × 10-2). CONCLUSIONS/INTERPRETATION:An adult-based GRS comprising 53 insulin resistance susceptibility SNPs associates with insulin resistance, markers of the metabolic syndrome and altered fat distribution in a sample of Danish children and adolescents who were overweight or obese.

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Project description:Sanye Tablet (SYT) is a patent prescription widely used in treating T2D and pre-diabetes, especially T2D comorbid with hypertriglyceridemia, for many years in China. However, the underlying mechanism that accounts for the anti-diabetic potential of SYT by regulating lipid-related intermediates remains to be elucidated. This study aimed to investigate the mechanism of SYT on lipid metabolism and insulin sensitivity in high-fat diet (HFD)-induced obese mice by means of combining lipidomics and proteomics. The obese mice models were developed via HFD feeding for 20 consecutive weeks. Mice in the treatment group were given metformin and SYT respectively, and the effects of SYT on body weight, blood glucose, insulin sensitivity, fat accumulation in the organs, and pathological changes in the liver were monitored. Lipid metabolism was examined by lipidomics. Further determination of signaling pathways was detected by proteomics. The biological contributions of the compounds detected in SYT's chemical fingerprint were predicted by network pharmacology. SYT treatment reduced body weight, inhibited viscera and hepatic steatosis lipid accumulation, and prevented insulin resistance. Furthermore, it was found that circulatory inflammatory cytokines were reduced by SYT treatment. In addition, lipidomics analysis indicated that SYT targets lipid intermediates, including diacylglycerol (DAG) and Ceramide (Cer). Mechanistically, SYT positively affected these lipid intermediates by suppressing liver lipogenesis via downregulation of SREBP1/ACC and the JAK/STAT signaling pathway. Our results predicted that astragalin and rosmarinic acid might regulate the JAK-STAT pathway by targeting PIM2 and STAT1, respectively, while paeoniflorin and rosmarinic acid were likely to regulate inflammatory responses by targeting TNFα, IL-6, and IL-4 during T2D. Overall, our study provides supportive evidence for the mechanism of SYT's therapeutic effect on dysregulated lipid metabolism in diabesity.

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Intraperitoneal fat and insulin resistance in obese adolescents.

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Intraperitoneal fat and insulin resistance in obese adolescents.

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