Genetic Determinant for Amino Acid Metabolites and Changes in Body Weight and Insulin Resistance in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) Trial
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CitationXu, M., Q. Qi, J. Liang, G. A. Bray, F. B. Hu, F. M. Sacks, and L. Qi. 2013. “Genetic Determinant for Amino Acid Metabolites and Changes in Body Weight and Insulin Resistance in Response to Weight-Loss Diets: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) Trial.” Circulation 127 (12) (February 27): 1283–1289. doi:10.1161/circulationaha.112.000586.
AbstractBACKGROUND: Circulating branched-chain amino acids and aromatic amino acids were recently related to insulin resistance and diabetes mellitus in prospective cohorts. We tested the effects of a genetic determinant of branched-chain amino acid/aromatic amino acid ratio on changes in body weight and insulin resistance in a 2-year diet intervention trial. METHODS AND RESULTS: We genotyped the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 near the PPM1K gene in 734 overweight or obese adults who were assigned to 1 of 4 diets varying in macronutrient content. At 6 months, dietary fat significantly modified genetic effects on changes in weight, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) after adjustment for the confounders (all P for interaction ≤0.006). Further adjustment for weight change did not appreciably change the interactions for fasting insulin and HOMA-IR. In the high-fat diet group, the C allele was related to less weight loss and smaller decreases in serum insulin and HOMA-IR (all P ≤ 0.02 in an additive pattern), whereas an opposite genotype effect on changes in insulin and HOMA-IR was observed in the low-fat diet group (P=0.02 and P=0.04, respectively). At 2 years, the gene-diet interactions remained significant for weight loss (P=0.008) but became null for changes in serum insulin and HOMA-IR resulting from weight regain. CONCLUSIONS: Individuals carrying the C allele of the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 may benefit less in weight loss and improvement of insulin sensitivity than those without this allele when undertaking an energy-restricted high-fat diet. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00072995.
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