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Paul Franks

Paul Franks

Principal investigator

Paul Franks

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

Author

  • 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.

Department/s

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

Publishing year

2021

Language

English

Pages

1030-1040

Publication/Series

Diabetes, Obesity and Metabolism

Volume

23

Issue

4

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

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

Status

Published

Research group

  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 1462-8902