Marked resistance of the ability of insulin to decrease arterial stiffnesscharacterizes human obesity

We tested the hypothesis that insulin has effects on large artery stiffness in addition to its slow vasodilatory effect on resistance vessels in skele tal muscle, and whether such an effect might be altered in obesity. Eight n onobese (aged 25 +/- 1 years, BMI 22.7 +/- 0.4 kg/m(2)) and eight obese (ag ed 27 +/- 2 years, BMI 30.6 +/- 0.9 kg/m(2)) men were studied under normogl ycemic-hyperinsulinemic (sequential 2-h insulin infusions of 1 [step 1] and 2 [step 2] mU.kg(-1).min(-1)) conditions, and another seven men participat ed in a saline control study. Central aortic pressure waves were synthesize d from those recorded in the periphery using applanation tonometry and a va lidated reverse transfer function every 30 min. This allowed determination of augmentation (the pressure difference between early and late systolic pr essure peaks) and the augmentation index (augmentation divided by pulse pre ssure), a measure of arterial stiffness. Whole-body glucose uptake was redu ced by 48 (step 1) and 41% (step 2) (P < 0.01) in the obese subjects versus the nonobese subjects. Basal forearm blood flow averaged 2.5 +/- 0.2 and 2 .6 +/- 0.2 ml.dl(-1).min(-1) in the obese and nonobese subjects, respective ly (NS), Insulin induced a significant increase in forearm blood flow after 2.5 h (3.6 +/- 0.4 ml.dl(-1).min(-1), P < 0.05 vs. basal) in the nonobese subjects and after 4 h in the obese subjects (3.2 +/- 0.2, P < 0.05), In co ntrast to these slow changes in peripheral blood flow, augmentation and the augmentation index decreased significantly in the nonobese subjects after 1 h (-3.0 +/- 1.6 mmHg and -10.0 +/- 5.4%, respectively, P < 0.001 vs. basa l), but remained unchanged until 3 h in the obese subjects. Percent fat (r = 0.86, P < 0.0001) and whole-body glucose uptake (r = -0.72, P < 0.01) cor related with the change in the augmentation index by insulin. These data de monstrate temporal dissociation in insulin's vascular actions. Insulin's ef fect to decrease arterial stiffness in nonobese subjects (a decrease in wav e reflection) is observed under physiological conditions and precedes a slo w vasodilatory effect in the periphery. In the obese subjects, insulin's no rmal effect to decrease central wave reflection is severely blunted. The de gree of impairment in this novel vascular action of insulin is closely corr elated with the degree of obesity and insulin action on glucose uptake.