Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the diabetes prevention program

Abstract

OBJECTIVE - We tested genetic associations with weight loss and weight regain in the Diabetes Prevention Program, a randomized controlled trial of weight loss-inducing interventions (lifestyle and metformin) versus placebo. RESEARCH DESIGN AND METHODS - Sixteen obesity-predisposing single nucleotide polymorphisms (SNPs) were tested for association with short-term (baseline to 6 months) and long-term (baseline to 2 years) weight loss and weight regain (6 months to study end). RESULTS - Irrespective of treatment, the Ala12 allele at PPARGassociated with short- and long-term weight loss (-0.63 and -0.93 kg/allele, P ≤ 0.005, respectively). Gene-treatment interactions were observed for short-term (LYPLAL1 rs2605100, P lifestyle*SNP = 0.032; GNPDA2 rs10938397, P lifestyle*SNP = 0.016; MTCH2 rs10838738, P lifestyle*SNP = 0.022) and long-term (NEGR1 rs2815752, P metformin*SNP = 0.028; FTO rs9939609, P lifestyle*SNP = 0.044) weight loss.Three of 16 SNPs were associated with weight regain (NEGR1 rs2815752, BDNF rs6265, PPARG rs1801282), irrespective of treatment. TMEM18 rs6548238 and KTCD15 rs29941 showed treatment-specific effects (P lifestyle*SNP < 0.05). CONCLUSIONS - Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention. © 2012 by the American Diabetes Association.