American Diabetes Association
Supplementary_Material_R3_1207.pdf (652.76 kB)

Modifiable Lifestyle Factors, Genetic Risk, and Incident Peripheral Artery Disease among Individuals with Type 2 Diabetes: A Prospective Study

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posted on 2024-01-05, 20:37 authored by Kai ZhuKai Zhu, Frank Qian, QI LU, Rui LiRui Li, Zixin Qiu, Lin LiLin Li, Ruyi LiRuyi Li, Hancheng YuHancheng Yu, Yulei Deng, Kun YangKun Yang, An pan, Gang LiuGang Liu

Objectives: To prospectively evaluate the association between modifiable lifestyle factors and peripheral artery disease (PAD) among individuals with type 2 diabetes (T2D). Research design and methods: We included 14,543 individuals with T2D from the UK Biobank. We defined a weighted healthy lifestyle score using non-smoking, regular physical activity, high-quality diet, moderate alcohol consumption, optimal waist-to-hip ratio, and adequate sleep duration, and categorized into unfavorable, intermediate, and favorable lifestyle. We created a genetic risk score (GRS) using 19 SNPs previously found to be associated with PAD. We modeled the association between lifestyle score and PAD, overall and stratified by PAD genetic susceptibility. Results: After a median 13.5 years of follow-up, 628 incident cases of PAD were documented. A linear inverse association between the weighted lifestyle score and PAD was observed, with a HR (95% CI) of 0.27 (0.19, 0.38) for favorable compared to unfavorable lifestyle (Ptrend<0.0001). An estimated 58.3% (45.0%, 69.1%) of PAD in this population could be potentially avoidable if all participants attained a favorable lifestyle. Moreover, the PAD GRS was associated with increased PAD risk [HR (95%CI) per-SD increment: 1.13 (1.03, 1.23)]. A favorable lifestyle was able to partially mitigate the excess risk of PAD associated with higher GRS, albeit non-significant interaction. Several biomarkers in the lipid metabolism, hepatic/renal function, and systemic inflammation pathways collectively explained 13.3% (8.5%, 20.1%) of the association between weighted lifestyle score and PAD. Conclusion: A favorable lifestyle was associated with lower risk of PAD among individuals with T2D, independent of genetic predisposition to PAD.


GL is supported by grants from National Natural Science Foundation of China (82273623 and 82073554), the Hubei Province Science Fund for Distinguished Young Scholars (2021CFA048), and the Fundamental Research Funds for the Central Universities (2021GCRC076). AP is supported by grants from National Natural Science Foundation of China (81930124, 82021005, and 82192902), and the Fundamental Research Funds for the Central Universities (2021GCRC075). The Funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. All authors have reported that they have no relationships relevant to the contents of this paper to disclose.


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