Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program

Diabetes Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Diabetes care (Impact Factor: 8.42). 12/2011; 35(2):363-6. DOI: 10.2337/dc11-1328
Source: PubMed


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.
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).
Irrespective of treatment, the Ala12 allele at PPARG associated 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).
Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention.

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Available from: Jeanne M Mccaffery
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    • "Thus, many have sought to understand the mechanisms through which these processes occur in anticipation that this might aid in the prevention of diabetes. In a recent study from the Diabetes Prevention Program (DPP) [71], a multiethnic randomized clinical trial of weight loss for diabetes prevention [69], we identified a number of genetic markers that predict weight regain after intentional weight loss through lifestyle modification or metformin treatment. Two of these variants (BDNF rs6265, PPARG Pro12Ala/rs1801282) conveyed effects on weight regain that were statistically significant after adjustment for multiple hypothesis testing and were evident in the entire multiethic cohort and in Non-Hispanic Whites only, mitigating the possibility that confounding by population stratification underlies these effects. "
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