A possible link between endothelial dysfunction and insulin resistance in hypertension. A LIFE substudy

Background: We wanted to investigate whether insulin resistance and time to steady state during isoglycemic clamp were associated with endothelial dys function, peripheral vascular remodeling and forearm brood flow (FBF) in pa tients with longstanding hypertension. Methods: In 43 unmedicated, hyperten sive patients with electrocardiographic-defined left ventricular hypertroph y we performed a 2-h oral glucose tolerance test and a 3-h isoglycemic hype rinsulinemic clamp with measurements of circulating plasma epinephrine and FBF by plethysmography. Delayed steady state was assessed by measuring the increase in insulin sensitivity from the second to the third hour of clampi ng. We measured 24-h ambulatory blood pressure, minimal forearm vascular re sistance (MFVR) by plethysmography, media:lumen ratio (MLR) and acetylcholi ne-induced relaxation (AIR) in isolated, subcutaneous resistance arteries b y myography. Results: Insulin sensitivity after 2 and 3 h of clamping was n ot related to maximal AIR, MLR, MFVR or FBF. The increase in insulin sensit ivity in men was negatively correlated to maximal AIR (r = -0.36, p < 0.05) , and was independently correlated to relative changes in FBF (beta = 0.46) and in circulating epinephrine (beta = 0.33; adj. R-2 = 0.33, p < 0.001). Conclusions: Insulin sensitivity was not correlated to parameters of periph eral vascular remodeling, endothelial function or microvascular rarefaction in patients with longstanding hypertension and left ventricular hypertroph y. However, the action of insulin on peripheral glucose uptake was influenc ed by endothelial dysfunction (delayed transcapillary insulin transport) an d by changes in and/or redistribution of blood flow suggesting a link betwe en vascular function and insulin sensitivity.