BACKGROUND: 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.
RCT Entities:
BACKGROUND: 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.
Authors: M Emoto; Y Nishizawa; K Maekawa; Y Hiura; H Kanda; T Kawagishi; T Shoji; Y Okuno; H Morii Journal: Diabetes Care Date: 1999-05 Impact factor: 19.112
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Authors: R L Anderson; R F Hamman; P J Savage; M F Saad; A Laws; W W Kades; R E Sands; W Cefalu Journal: Am J Epidemiol Date: 1995-10-01 Impact factor: 4.897
Authors: Laura P Svetkey; Victor J Stevens; Phillip J Brantley; Lawrence J Appel; Jack F Hollis; Catherine M Loria; William M Vollmer; Christina M Gullion; Kristine Funk; Patti Smith; Carmen Samuel-Hodge; Valerie Myers; Lillian F Lien; Daniel Laferriere; Betty Kennedy; Gerald J Jerome; Fran Heinith; David W Harsha; Pamela Evans; Thomas P Erlinger; Arline T Dalcin; Janelle Coughlin; Jeanne Charleston; Catherine M Champagne; Alan Bauck; Jamy D Ard; Kathleen Aicher Journal: JAMA Date: 2008-03-12 Impact factor: 56.272
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