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

<b>Objective: </b>We aimed to investigate prospective associations of pulse wave <a>arterial stiffness index (ASI) and pulse pressure (PP)</a> with T2D, and assessed the modification effect of genetics. <p><b>Research design and methods:</b> <a>We included 152 611 participants free of diabetes or cardiovascular disease in the UK Biobank.</a> <a>All participants had ASI and blood pressure measurements collected at baseline visit.</a> Totally, 37 single nucleotide polymorphisms were used to calculate the genetic risk score (GRS) of T2D.</p> <p><b>Results:</b> <a>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. </a>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 (<i>P</i> interaction=0.008). While the interaction between PP and GRS was non-significant (<i>P</i> interaction=0.55).</p> <b>Conclusions</b>: 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.