Abstract P155: Modifiable Lifestyle Factors, Genetic Risk, and Incident Peripheral Artery Disease Among Individuals With Type 2 Diabetes: A Prospective Study

Abstract

Background: Individuals with type 2 diabetes (T2D) are at elevated risk of developing peripheral artery disease (PAD). Whether healthy lifestyle can reduce this risk, particularly in individuals genetically predisposed to PAD, is unknown. Aims: To evaluate the association between modifiable lifestyle factors with incident PAD among individuals with T2D, both overall and stratified by genetic risk of PAD. Methods: We included 19,368 individuals with T2D from the UK Biobank, who were free of PAD and cardiovascular disease. We defined a low-risk lifestyle score with 1 point assigned for each of the following: non-current smoking, regular physical activity, adhering to a high-quality diet, moderate alcohol consumption, maintaining a normal waist-hip ratio, sleeping 7-8 hours/day. A polygenic risk score (PRS) including 19 single nucleotide polymorphisms was constructed. Multivariable-adjusted Cox models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: After a median 7.6 years of follow-up, 325 incident cases of PAD were documented. There was an inverse association between the low-risk lifestyle score and incident PAD, with HR (95%CI) of 0.73 (0.54, 1.03), 0.43 (0.30, 0.60), and 0.42 (0.30, 0.60) for 2, 3, and ≥4 compared with ≤1. The PRS was associated with an increased risk of PAD, with HR (95%CI) of 1.16 (1.03, 1.31) per-SD increment. A more favorable lifestyle was able to partially mitigate the risk of increased genetic susceptibility to PAD ( Figure 1 ). In mediation analysis, 42.4% of the association could be attributable to risk factors including inflammation, atherogenic lipoproteins, and impaired hepatic/renal function. Conclusion: A combined set of modifiable lifestyle factors was associated with a substantially lower risk of incident PAD among individuals with T2D and may be able to partially mitigate an underlying genetic predisposition for PAD. Our findings highlight the importance of improving adherence to these factors in the primary prevention of PAD among individuals with T2D.