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Paul Franks

Paul Franks

Principal investigator

Paul Franks

Interaction Between Type 2 Diabetes Prevention Strategies and Genetic Determinants of Coronary Artery Disease on Cardiometabolic Risk Factors

Author

  • Jordi Merino
  • Kathleen A. Jablonski
  • Josep M. Mercader
  • Steven E. Kahn
  • Ling Chen
  • Maegan Harden
  • Linda M. Delahanty
  • Maria Rosario G. Araneta
  • Geoffrey A. Walford
  • Suzanne B.R. Jacobs
  • Uzoma N. Ibebuogu
  • Paul W. Franks
  • William C. Knowler
  • Jose C. Florez

Summary, in English

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (Pinteraction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.

Department/s

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

Publishing year

2020

Language

English

Pages

112-120

Publication/Series

Diabetes

Volume

69

Issue

1

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes
  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 1939-327X