Impact of metabolic indices on central artery stiffness: independent association of insulin resistance and glucose with aortic pulse wave velocity

Abstract

Non-invasive measures of aortic stiffness reflect vascular senescence and predict outcome in diabetes. Glucose-mediated elastic artery sclerosis may play an integral role in the development of macrovascular complications. We used carotid-femoral pulse wave velocity ((cf)PWV) to quantify independent associations of fasting glucose, post-challenge glucose and derived insulin resistance (HOMA-IR) with aortic stiffness. (cf)PWV was measured using a 4 MHz continuous wave Doppler ultrasound probe within groups with newly identified age- and sex-matched normal glucose metabolism (NGM), impaired glucose regulation (IGR) and diabetes mellitus populations (n = 570, mean age 59.1, 56% male). After multivariate adjustment, IGR and diabetes were associated with significant aortic stiffening compared with NGM (adjusted (cf)PWV+/-SE: NGM, 9.15 +/- 0.12 m/s; IGR 9.76 +/- 0.11 m/s, p < 0.001; diabetes, 9.89 +/- 0.12 m/s, p < 0.001). IGR stratification indicated that impaired fasting glucose (IFG; 9.71 +/- 0.12 m/s) and post-challenge (impaired glucose tolerance; 9.82 +/- 0.24 m/s) categories had similar (cf)PWV (p = 0.83). Modelled predictors of (cf)PWV were used to assess independent metabolic associations with arterial stiffness. Fasting glucose concentration (beta = 0.10; 95% CI 0.05, 0.18; p = 0.003), 2 h post-challenge glucose (beta = 0.14; 95% CI 0.02, 0.23; p < 0.001) and HOMA-IR (beta = 0.20, 95% CI 0.05, 0.53; p < 0.001) were independently related to (cf)PWV after adjustment for age, sex, mean arterial pressure, heart rate, body mass index, renal function and antihypertensive medication. IGR characterised by fasting or post-challenge hyperglycaemia is associated with significant vascular stiffening. Post-challenge glucose and HOMA-IR are the most powerful metabolic predictors of arterial stiffness, implying hyperglycaemic excursion and insulin resistance play important roles in the pathogenesis of arteriosclerosis.