Non-insulin-dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes: The ARIC study

Background: Cardiovascular diseases are the most common cause of disability and death among subjects with non-insulin-dependent diabetes mellitus (NIDDM). The atherosclerotic process begins during the prediabetic phase characterized by impaired glucose tolerance, hyperinsulinemia, and insulin resistance. In vitro studies have suggested that glucose and insulin can substantially alter the structure and function of the arterial wall and affect the development of atherosclerosis. Methods and Results: We performed a cross-sectional study of the relation of arterial stiffness indexes with glucose tolerance and serum insulin concentration. Several indexes of common carotid artery stiffness were assessed with noninvasive ultrasound methods in a biracial sample of 4701 men and women 45 to 64 years of age in the Atherosclerosis Risk in Communities (ARIC) Study. Arterial compliance (AC), stiffness index (SI), pressure-strain elastic modulus (Ep), and Young's elastic modulus (YEM) were calculated. YEM includes wall (intima-media) thickness and thus gives an estimate of arterial stiffness controlling for wall thickness. All indexes of arterial stiffness were higher with increasing concentrations of fasting glucose. This finding was consistent in both black and white examinees and in both sexes. A 25% increase in fasting glucose (approximately 1 SD) was associated in nondiabetic white men with a 5.8% (95% CI, -9.6% to -1.9%; P=.004) decrease in AC and increases of 5.8% (95% CI, 2.0% to 9.7%; P=.002) in SI, 11.3% (95% CI, 6.9% to 15.9%; P<.001) in Ep, and 11.2% (95% CI, 6.2% to 16.6%; P<.001) in YEM. In nondiabetic white woman, the corresponding predicted changes were a decrease of 15.0% (95% CI, -18.2% to - 11.7%; P<.001) in AC and increases of 16.6% (95% CI, 12.5% to 20.8%; P<.001) in SI, 23.2% (95% CI, 18.4% to 28.2%; P<.001) in Ep, and 19.2% (95% CI, 14.0% to 24.7%; P<.001) in YEM. Glucose and insulin contributed synergistically to the increase in stiffness indexes. Insulin and triglycerides also had a synergistic association with stiffness indexes. Conclusions: Our findings are compatible with the view that persons with NIDDM or borderline glucose intolerance have stiffer arteries than their counterparts with normal glucose tolerance and that the decreased elasticity is independent of artery, wall thickness. The joint effect of elevated glucose, insulin, and triglycerides can have a considerable impact on arterial stiffness and play an important role in the early pathophysiology of macrovascular disease in NIDDM.