Diabetes and Risk of Arterial Stiffness: A Mendelian Randomization Analysis

We aimed to explore the causal association between type 2 diabetes (T2D) and increased arterial stiffness. We performed a Mendelian randomization (MR) analysis in 11, 385 participants from a well-defined community study in Shanghai during 2011-2013. We genotyped 34 T2D-associated common variants identified in East Asians and created a genetic risk score (GRS). We assessed arterial stiffness noninvasively with the measurement of brachial-ankle pulse wave velocity (baPWV). We used the instrumental variable (IV) estimator to qualify the causal relationship between T2D and increased arterial stiffness. We found each 1-SD increase in T2DGRS was associated with 6% higher risk in increased arterial stiffness (95% CI 1. 01, 1. 12), after adjustment of other metabolic confounders. Using T2DGRS as the IV, we demonstrated a causal relationship between T2D and arterial stiffening (odds ratio 1. 24, 95% CI 1. 06, 1. 47; P = 0. 008). When categorizing the genetic loci according to their effect on insulin secretion or resistance, we found genetically determined decrease in insulin secretion was associated with increase in baPWV (βIV = 122. 3 cm/s, 95% CI 41. 9, 204. 6; P = 0. 0005). In conclusion, our results provide evidence supporting a causal association between T2D and increased arterial stiffness in a Chinese population.