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Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

ABSTRACT: UNLABELLED:What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children and their metabolomic profiles are consistent with increased BCAA catabolism. Elevations in BCAAs in children are positively associated with insulin resistance measured 18 months later, independent of their initial body mass index. BACKGROUND:Branched-chain amino acid (BCAA) concentrations are elevated in response to overnutrition, and can affect both insulin sensitivity and secretion. Alterations in their metabolism may therefore play a role in the early pathogenesis of type 2 diabetes in overweight children. OBJECTIVE:To determine whether paediatric obesity is associated with elevations in fasting circulating concentrations of BCAAs (isoleucine, leucine and valine), and whether these elevations predict future insulin resistance. METHODS:Sixty-nine healthy subjects, ages 8-18 years, were enrolled as a cross-sectional cohort. A subset of subjects who were pre- or early-pubertal, ages 8-13 years, were enrolled in a prospective longitudinal cohort for 18 months (n = 17 with complete data). RESULTS:Elevations in the concentrations of BCAAs were significantly associated with body mass index (BMI) Z-score (Spearman's Rho 0.27, P = 0.03) in the cross-sectional cohort. In the subset of subjects that followed longitudinally, baseline BCAA concentrations were positively associated with homeostasis model assessment for insulin resistance measured 18 months later after controlling for baseline clinical factors including BMI Z-score, sex and pubertal stage (P = 0.046). CONCLUSIONS:Elevations in the concentrations of circulating BCAAs are significantly associated with obesity in children and adolescents, and may independently predict future insulin resistance.

SUBMITTER: McCormack SE

PROVIDER: S-EPMC3519972 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

McCormack S E SE Shaham O O McCarthy M A MA Deik A A AA Wang T J TJ Gerszten R E RE Clish C B CB Mootha V K VK Grinspoon S K SK Fleischman A A

Pediatric obesity 20120907 1

<h4>Unlabelled</h4>What is already known about this subject Circulating concentrations of branched-chain amino acids (BCAAs) can affect carbohydrate metabolism in skeletal muscle, and therefore may alter insulin sensitivity. BCAAs are elevated in adults with diet-induced obesity, and are associated with their future risk of type 2 diabetes even after accounting for baseline clinical risk factors. What this study adds Increased concentrations of BCAAs are already present in young obese children a ...[more]

PMID: 22961720

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Project description:BackgroundBranched-chain amino acid (BCAA) concentrations in the blood have been correlated with insulin resistance, but this relation throughout gestation (period in which insulin resistance typically increases) is unclear.ObjectiveThe objective of this study was to determine the associations between changes in BCAA concentrations and estimates of insulin resistance throughout gestation.MethodsSerum BCAA (Leu, Ile, Val) concentrations and insulin resistance/sensitivity [i.e., homeostatic model assessment-2 of insulin resistance (HOMA2-IR), estimated metabolic clearance rate (MCR) of glucose, and estimated first- and second-phase insulin responses] were assessed at early (EP; 8.5 ± 0.2 wk) and/or late (LP; 29.2 ± 0.8 wk) pregnancy in 53 healthy women from the Glowing cohort. Adjusted Spearman correlations were used to evaluate the association between BCAA and insulin resistance/sensitivity measures at EP and LP, adjusted for body fat percentage and gestational weight gain (GWG). A multiple linear regression analysis was used to assess the association between changes in HOMA2-IR and BCAAs throughout gestation. Groups were made post hoc based on the mean percentage change (10% decrease) in Leu throughout gestation, creating a group with a ≥10% decrease in LeuLP-EP (BELOW) and a <10% decrease in LeuLP-EP (ABOVE), and Student's t tests were performed to assess differences between groups.ResultsLeu and Ile concentrations positively correlated with HOMA2-IR at both time points, but these relations at EP disappeared/weakened when adjusted for body fat percentage. From EP to LP, the change in Leu (LeuLP-EP) was negatively associated with the change in HOMA2-IR (HOMA2-IRLP-EP) (β = -0.037, P = 0.006). MCR was lower in the BELOW group compared with the ABOVE group, whereas there was no difference in HOMA2-IR between groups.ConclusionsIn this pregnancy cohort, BCAA concentrations decreased throughout gestation, whereas the mean insulin resistance did not change. These data do not support a connection between changes in blood BCAA concentrations and estimates of insulin resistance in pregnant women. This trial is registered at clinicaltrials.gov as NCT01131117.

Dataset Information

Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

Publications

Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents.

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