Genetic predictors of weight loss and weight regain after intensive lifestyle modification, metformin treatment, or standard care in the Diabetes Prevention Program.

Academic Article


  • 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 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). CONCLUSIONS: Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention.
  • Authors

    Published In

  • Diabetes Care  Journal
  • Keywords

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Weight, Brain-Derived Neurotrophic Factor, Cell Adhesion Molecules, Neuronal, Diabetes Mellitus, GPI-Linked Proteins, Genetic Predisposition to Disease, Genotype, Humans, Life Style, Lysophospholipase, Membrane Proteins, Metformin, Mitochondrial Membrane Transport Proteins, PPAR gamma, Polymorphism, Single Nucleotide, Proteins, Weight Gain, Weight Loss
  • Digital Object Identifier (doi)

    Pubmed Id

  • 9989443
  • Author List

  • Delahanty LM; Pan Q; Jablonski KA; Watson KE; McCaffery JM; Shuldiner A; Kahn SE; Knowler WC; Florez JC; Franks PW
  • Start Page

  • 363
  • End Page

  • 366
  • Volume

  • 35
  • Issue

  • 2