Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here:

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Paul Franks

Paul Franks

Principal investigator

Paul Franks

Interaction of diabetes genetic risk and successful lifestyle modification in the Diabetes Prevention Programme


  • Sridharan Raghavan
  • Kathleen Jablonski
  • Linda M. Delahanty
  • Nisa M. Maruthur
  • Aaron Leong
  • Paul W. Franks
  • William C. Knowler
  • Jose C. Florez
  • Dana Dabelea

Summary, in English

Aim: To test whether diabetes genetic risk modifies the association of successful lifestyle changes with incident diabetes. Materials and methods: We studied 823 individuals randomized to the intensive lifestyle intervention (ILS) arm of the Diabetes Prevention Programme who were diabetes-free 1 year after enrolment. We tested additive and multiplicative interactions of a 67-variant diabetes genetic risk score (GRS) with achievement of three ILS goals at 1 year (≥7% weight loss, ≥150 min/wk of moderate leisure-time physical activity, and/or a goal for self-reported total fat intake) on the primary outcome of incident diabetes over 3 years of follow-up. Results: A lower GRS and achieving each or all three ILS goals were each associated with lower incidence of diabetes (all P < 0.05). Additive interactions were significant between the GRS and achievement of the weight loss goal (P < 0.001), physical activity goal (P = 0.02), and all three ILS goals (P < 0.001) for diabetes risk. Achievement of all three ILS goals was associated with 1.8 (95% CI 0.3, 3.4), 3.1 (95% CI 1.5, 4.7), and 3.9 (95% CI 1.6, 6.2) fewer diabetes cases/100-person-years in the first, second and third GRS tertiles (P < 0.001 for trend). Multiplicative interactions between the GRS and ILS goal achievement were significant for the diet goal (P < 0.001), but not for weight loss (P = 0.18) or physical activity (P = 0.62) goals. Conclusions: Genetic risk may identify high-risk subgroups for whom successful lifestyle modification is associated with greater absolute reduction in the risk of incident diabetes.


  • Genetic and Molecular Epidemiology
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year







Diabetes, Obesity and Metabolism





Document type

Journal article




  • Endocrinology and Diabetes
  • Public Health, Global Health, Social Medicine and Epidemiology



Research group

  • Genetic and Molecular Epidemiology


  • ISSN: 1462-8902