Sex differences in biomarkers associated with insulin resistance in obese adolescents: metabolomic profiling and principal components analysis.

Journal Article (Journal Article)

OBJECTIVE: Obesity and insulin resistance (IR) predispose to type 2 diabetes mellitus. Yet only half of obese adolescents have IR and far fewer progress to type 2 diabetes mellitus. We hypothesized that amino acid and fatty acid metabolites may serve as biomarkers or determinants of IR in obese teens. RESEARCH DESIGN AND METHODS: Fasting blood samples were analyzed by tandem mass spectrometry in 82 obese adolescents. A principal components analysis and multiple linear regression models were used to correlate metabolic components with surrogate measures of IR: homeostasis model assessment index of insulin resistance (HOMA-IR), adiponectin, and triglyceride (TG) to high-density lipoprotein (HDL) ratio. RESULTS: Branched-chain amino acid (BCAA) levels and products of BCAA catabolism were higher (P < .01) in males than females with comparable body mass index (BMI) z-score. In multivariate analyses, HOMA-IR in males correlated positively with BMI z-score and a metabolic signature containing BCAA, uric acid, and long-chain acylcarnitines and negatively with byproducts of complete fatty acid oxidation (R(2) = 0.659, P < .0001). In contrast, only BMI z-score correlated with HOMA-IR in females. Adiponectin correlated inversely with BCAA and uric acid (R(2) = 0.268, P = .0212) in males but not females. TG to HDL ratio correlated with BMI z-score and the BCAA signature in females but not males. CONCLUSIONS: BCAA levels and byproducts of BCAA catabolism are higher in obese teenage boys than girls of comparable BMI z-score. A metabolic signature comprising BCAA and uric acid correlates positively with HOMA-IR in males and TG to HDL ratio in females and inversely with adiponectin in males but not females. Likewise, byproducts of fatty acid oxidation associate inversely with HOMA-IR in males but not females. Our findings underscore the roles of sex differences in metabolic function and outcomes in pediatric obesity.

Full Text

Duke Authors

Cited Authors

  • Newbern, D; Gumus Balikcioglu, P; Balikcioglu, M; Bain, J; Muehlbauer, M; Stevens, R; Ilkayeva, O; Dolinsky, D; Armstrong, S; Irizarry, K; Freemark, M

Published Date

  • December 2014

Published In

Volume / Issue

  • 99 / 12

Start / End Page

  • 4730 - 4739

PubMed ID

  • 25202817

Pubmed Central ID

  • PMC4328030

Electronic International Standard Serial Number (EISSN)

  • 1945-7197

Digital Object Identifier (DOI)

  • 10.1210/jc.2014-2080


  • eng

Conference Location

  • United States