Association between arterial stiffness/remodeling and new-onset type 2 diabetes mellitus in general population

Objective: We studied if large artery stiffness is involved in type 2 diabetes pathogenesis. We also investigated the effect of genetic risk for type 2 diabetes in these associations and the causality. Research design and Methods: In the prospective population-based Rotterdam Study (n = 3,055; mean age, 67.2 years), markers of aortic and carotid stiffnesses and measures of arterial remodeling were assessed. Cox proportional hazard regression analysis estimated the associations between arterial stiffness measures with incident type 2 diabetes. We used 403 single nucleotide polymorphisms to calculate the genetic risk score (GRS) for type 2 diabetes. We adopted Mendelian randomization (MR) analysis to evaluate the causal associations. Results: Over a median follow-up of 14.0 years, higher carotid-femoral pulse wave velocity (hazard ratio,1.18; 95 %CI: 1.04–1.35), carotid distensibility coefficient (1.17; 1.04–1.32), and carotid intima-media thickness (1.15; 1.01–1.32) were independently associated with incident diabetes. The associations were stronger among individuals with a higher GRS for type 2 diabetes. MR analysis did not support the causality of the observed associations. Conclusions: Elevated arterial stiffness is independently associated with incident type 2 diabetes. For most arterial stiffness markers, the associations with incident type 2 diabetes were more robust in individuals with a higher GRS for diabetes.