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

  • Linda M. Delahanty
  • Qing Pan
  • Icatiileen A. Jablonski
  • Karol E. Watson
  • Jeanne M. McCaffery
  • Alan Shuldiner
  • Steven E. Kahn
  • William C. Knowler
  • Jose C. Florez
  • Paul Franks
Publishing year: 2012
Language: English
Pages: 363-366
Publication/Series: Diabetes Care
Volume: 35
Issue: 2
Document type: Journal article
Publisher: American Diabetes Association

Abstract english

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.


  • Endocrinology and Diabetes


  • Genetic and Molecular Epidemiology
  • ISSN: 1935-5548
Paul Franks
E-mail: paul [dot] franks [at] med [dot] lu [dot] se

Principal investigator

Genetic and Molecular Epidemiology

+46 40 39 11 49



Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00