Association of physical activity with lower type 2 diabetes incidence is weaker among individuals at high genetic risk

C. Yann, Klimentidis Zhao, Chen Amit Arora, Chiu Hsieh Hsu

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Aims/hypothesis We examined whether or not the association of physical activity with type 2 diabetes incidence differs according to several types of genetic susceptibility. Methods In a large prospective cohort with 821 incident cases of type 2 diabetes, we examined interactions of physical activity with: (1) each of 65 type 2 diabetes-associated single nucleotide polymorphisms (SNPs); (2) a genetic risk score (GRS) comprising all 65 SNPs; (3) two GRSs comprised of SNPs implicated in insulin resistance (IR) and insulin secretion; (4) GRSs for fasting insulin (FI) and fasting glucose. Results We found a significant interaction of physical activity and the type 2 diabetes GRS (pinteraction=0.016), suggesting a weaker protective effect of physical activity in those at high genetic risk. Based on the interactions observed with the IR GRS (pinteraction=0.046) and the FI GRS (pinteraction=0.042), it appears that the overall type 2 diabetes GRS interaction most likely occurs through genetic susceptibility to IR as opposed to insulin secretion. Furthermore, this interaction was more pronounced in women (pinteraction=0.0025) than in men (pinteraction=0.46). No single SNP stood out as displaying a strong interaction with physical activity. Conclusions/interpretation We conclude that although physical activity appears to have an overall protective effect on type 2 diabetes, this putative effect is weakest among individuals with high genetic risk for type 2 diabetes and IR.

Original languageEnglish (US)
Pages (from-to)2530-2534
Number of pages5
Issue number12
StatePublished - Oct 2 2014


  • Genetic risk
  • Insulin resistance
  • Interaction
  • Physical activity
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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