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

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 (p interaction= 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 (p interaction= 0.046) and the FI GRS (p interaction= 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 (p interaction= 0.0025) than in men (p interaction= 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)
JournalDiabetologia
DOIs
StateAccepted/In press - Oct 2 2014

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Type 2 Diabetes Mellitus
Exercise
Incidence
Single Nucleotide Polymorphism
Insulin Resistance
Insulin
Fasting
Genetic Predisposition to Disease
Glucose

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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abstract = "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 (p interaction= 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 (p interaction= 0.046) and the FI GRS (p interaction= 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 (p interaction= 0.0025) than in men (p interaction= 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.",
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AU - Amit Arora, Chen

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N2 - 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 (p interaction= 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 (p interaction= 0.046) and the FI GRS (p interaction= 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 (p interaction= 0.0025) than in men (p interaction= 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.

AB - 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 (p interaction= 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 (p interaction= 0.046) and the FI GRS (p interaction= 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 (p interaction= 0.0025) than in men (p interaction= 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.

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