Earlier Age at Type 2 Diabetes Diagnosis Is Associated With Increased Genetic Risk of Cardiovascular Disease
Hyunsuk Lee, Jaewon Choi, Na Yeon Kim, Jong‐Il Kim, Min Kyong Moon, Seunggeun Lee, Kyong Soo Park, Soo Heon Kwak
Abstract
OBJECTIVE: We investigated genetic risk of cardiovascular disease (CVD) by age at type 2 diabetes (T2D) diagnosis. RESEARCH DESIGN AND METHODS: We compared incident CVD events by age at T2D diagnosis using UK Biobank (N = 12,321) and the Seoul National University Hospital (SNUH) cohort (N = 1,165). Genetic risk was quantified using polygenic risk score (PRS). RESULTS: Individuals with earlier T2D diagnosis had higher CVD risk. In UK Biobank, the effect size of coronary artery disease (CAD) PRS on incident CAD was largest in individuals diagnosed with T2D at ages 30-39 years (hazard ratio 2.25; 95% CI 1.56-3.26) and decreased as age at diagnosis increased: ages 40-49 (1.51; 1.30-1.75), 50-59 (1.36; 1.24-1.50), and 60-69 years (1.30; 1.14-1.48) (Pinteraction = 0.0031). A similar trend was observed in the SNUH cohort. This increased genetic risk associated with earlier T2D diagnosis was largely mitigated by a healthy lifestyle. CONCLUSIONS: Individuals with an earlier T2D diagnosis have a higher genetic risk of CAD, and this information could be used to tailor lifestyle interventions.