Interaction between type 2 diabetes polygenic risk and physical activity on cardiovascular outcomes

Chia-Lin Lee; Tomohide Yamada; Wei-Ju Liu; Kazuo Hara; Shintaro Yanagimoto; Yuta Hiraike

doi:10.1093/eurjpc/zwae075

Interaction between type 2 diabetes polygenic risk and physical activity on cardiovascular outcomes

Eur J Prev Cardiol. 2024 Feb 22:zwae075. doi: 10.1093/eurjpc/zwae075. Online ahead of print.

Authors

Chia-Lin Lee^{1

2

3

4}, Tomohide Yamada^{5

6

7}, Wei-Ju Liu¹, Kazuo Hara⁶, Shintaro Yanagimoto⁸, Yuta Hiraike^{8

9}

Affiliations

¹ Intelligent Data Mining Laboratory, Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan.
² Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung 407219, Taiwan.
³ School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
⁴ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402204, Taiwan.
⁵ Yamada Diabetes Clinic, Tokyo 144-0052, Japan.
⁶ Division of Endocrinology and Metabolism, Jichi Medical University Saitama Medical Center, Saitama 330-8503, Japan.
⁷ Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
⁸ Division for Health Service Promotion, The University of Tokyo, Tokyo 113-0033, Japan.
⁹ The University of Tokyo Excellent Young Researcher Program, The University of Tokyo, Tokyo 113-8654, Japan.

PMID: 38386694
DOI: 10.1093/eurjpc/zwae075

Abstract

Aim: The beneficial effects of exercise on reducing the risk of cardiovascular disease are established. However, the potential interaction between genetic risk for type 2 diabetes and physical activity on cardiovascular outcomes remains elusive. We aimed to investigate the effect of type 2 diabetes genetic risk-physical activity interaction on cardiovascular outcomes in individuals with diabetes.

Methods: Using the UK Biobank cohort, we investigated the effect of type 2 diabetes genetic risk-physical activity interaction on 3-point and 4-point major adverse cardiovascular events (MACE), in 25,701 diabetic participants. We used a polygenic risk score for type 2 diabetes (PRS_T2D) as a measure of genetic risk for type 2 diabetes.

Results: We observed significant interaction between PRS_T2D and physical activity on cardiovascular outcomes (3-point MACE: P trend for interaction = 0.0081; 4-point MACE: P trend for interaction = 0.0037). Among participants whose PRS_T2D was in the first or second quartile, but not in the third or fourth quartile, each 10 metabolic equivalents (METs) hours per week of physical activity decreased the risk of 3-point or 4-point MACE. Furthermore, restricted cubic spline analysis indicated that intense physical activity (>80 METs hours per week, which was self-reported by 12.7% of participants) increased the risk of cardiovascular outcomes among participants whose PRS_T2D was in the fourth quartile. Subgroup analysis suggested that negative impact of intense physical activity was observed only in non-insulin users.

Conclusions: The beneficial effect of physical activity on cardiovascular outcomes were disappeared among those with high genetic risk for type 2 diabetes.

Keywords: Cardiovascular Complications; Gene-environment interaction; Physical activity; Polygenic risk score; Type 2 diabetes.

Plain language summary

The beneficial effects of exercise on reducing the risk of cardiovascular disease are established. However, whether genetic risk for type 2 diabetes influences the effect of physical activity on cardiovascular outcomes in individuals with diabetes remains elusive. We aimed to investigate interaction between genetic risk for type 2 diabetes and physical activity on major adverse cardiovascular events in individuals with diabetes. The beneficial effect of physical activity on cardiovascular outcomes were disappeared among diabetic individuals with high genetic risk for type 2 diabetes, due to significant gene-environment interaction; in this subpopulation, intense physical activity was associated with increased risk of cardiovascular outcomes. Personalized exercise recommendations tailored to avoid excessively intense exercise, in combination with genetic screening of high-risk individuals, would be required.