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

Abstract

OBJECTIVE We aimed to investigate prospective associations of pulse wave arterial stiffness index (ASI) and pulse pressure (PP) with type 2 diabetes (T2D) and assess the modifying effect of genetics. RESEARCH DESIGN AND METHODS We included 152,611 participants free of diabetes and cardiovascular disease in the UK Biobank. All participants had ASI and blood pressure measurements collected at baseline visit. In total, 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, 3,000 participants developed T2D. Per-SD increase in ASI was associated with a 3% higher T2D risk (95% CI 2–4%). The hazard ratio (HR) (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, because the elevated HR of T2D associated with high ASI was more evident among participants with higher GRS of T2D (P interaction = 0.008), whereas the interaction between PP and GRS was nonsignificant (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.