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Arterial Stiffness, Genetic Risk, and Type 2 Diabetes: A Prospective Cohort Study

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posted on 2022-01-25, 17:33 authored by Mengying Wang, Jie Huang, Tao Wu, Lu Qi
Objective: We aimed to investigate prospective associations of pulse wave arterial stiffness index (ASI) and pulse pressure (PP) with T2D, and assessed the modification effect of genetics.

Research design and methods: We included 152 611 participants free of diabetes or cardiovascular disease in the UK Biobank. All participants had ASI and blood pressure measurements collected at baseline visit. Totally, 37 single nucleotide polymorphisms were used to calculate the genetic risk score (GRS) of T2D.

Results: During a median follow‐up of 9.5 years, 3000 participants developed T2D. Per standard deviation increase in ASI was associated with a 3% higher T2D risk (95% confidence interval [CI]: 2%-4%). The hazard ratio (HR) and 95% CI of T2D was 1.58 (1.39-1.80) in the highest quintile group compared with the lowest quintile group of ASI. However, the association between PP and T2D was nonlinear. Compared with the lowest quintile group, the risk of T2D in higher quintile groups of PP was 0.91 (0.79-1.04), 0.98 (0.86-1.11), 1.15 (1.01-1.30), and 1.24 (1.10-1.41), respectively. Furthermore, we observed an interaction between ASI and genetic susceptibility to T2D, as the elevated HR of T2D associated with high ASI was more evident among participants with higher GRS of T2D (P interaction=0.008). While the interaction between PP and GRS was non-significant (P interaction=0.55).

Conclusions: ASI was associated with an elevated risk of T2D in a dose-response fashion, whereas PP and T2D showed a nonlinear J-shaped association. Additionally, the association between ASI and T2D was partially strengthened by higher genetic susceptibility to T2D.

Funding

This work was supported by grant from the National Key Research and Development Program of China (2020YFC2002900). M.W. is supported by China Postdoctoral Science Foundation (BX2021021).

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