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.

Download full-text


Available from: Jeanne M Mccaffery, Oct 10, 2015
1 Follower
17 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Type 2 diabetes (T2D) is one of the scourges of modern times, with many millions of people affected by the disease. Diabetes occurs most frequently in those who are overweight or obese. However, not all overweight and obese persons develop diabetes, and there are those who develop the disease who are lean and physically active. Certain ethnicities, especially indigenous populations, are at considerably higher risk of obesity and diabetes than those of white European ancestry. The patterns and distributions of diabetes have led some to speculate that the disease is caused by interactions between genetic and obesogenic lifestyle factors. Whilst to many this is a plausible explanation, remarkably little reliable evidence exists to support it. In this review, an overview of published literature relating to genetic and lifestyle risk factors for T2D is provided. The review also describes the concepts and rationale that have motivated the view that gene-lifestyle interactions cause diabetes and overviews the empirical evidence published to date to support this hypothesis.
    10/2012; 2012:482186. DOI:10.6064/2012/482186
  • Source
    • "Another study, a randomized controlled trial in overweight and obese adults (n = 3,234), investigated the effect of 16 novel GWAS obesity-susceptibility variants on weight loss during a 2-year intervention program. The researchers reported gene–lifestyle interactions for short-term and long-term weight loss [63•]. Altogether, these novel findings provide supportive information for the development of effective dietary intervention strategies based on genetic background. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is a complex multifaceted disease resulting from interactions between genetics and lifestyle. The proportion of phenotypic variance ascribed to genetic variance is 0.4 to 0.7 for obesity and recent years have seen considerable success in identifying disease-susceptibility variants. Although with the advent of genome-wide association studies the list of genetic variants predisposing to obesity has significantly increased the identified variants only explain a fraction of disease heritability. Studies of gene–environment interactions can provide more insight into the biological mechanisms involved in obesity despite the challenges associated with such designs. Epigenetic changes that affect gene function without DNA sequence modifications may be a key factor explaining interindividual differences in obesity, with both genetic and environmental factors influencing the epigenome. Disentangling the relative contributions of genetic, environmental and epigenetic marks to the establishment of obesity is a major challenge given the complex interplay between these determinants.
    09/2012; 1(3):184-196. DOI:10.1007/s13668-012-0022-2
  • Journal of pediatric endocrinology & metabolism: JPEM 02/2012; 25(1-2):1. DOI:10.1515/jpem-2012-0999 · 1.00 Impact Factor
Show more