Essential Hypertension Is Associated With Decreased Insulin Clearance and Insulin Resistance

Abstract

Essential hypertension is associated with multiple metabolic abnormalities, among them, hyperinsulinemia. This hyperinsulinemia is attributed to the presence of decreased insulin sensitivity (insulin resistance) with consequent compensatory insulin secretion. We tested the hypothesis that decreased insulin clearance is present in hypertensive subjects and contributes to hyperinsulinemia independently of the degree of insulin resistance. Seventy-five subjects were studied (48 hypertensive and 27 normotensive). Both groups were comparable in terms of age, body fat content, waist-to-hip ratio, and sex distribution. A primed continuous insulin infusion at 40 mU/m 2 per minute was performed. Glucose was maintained at baseline levels with the euglycemic clamp technique. Hypertensive subjects were characterized by decreased insulin sensitivity (insulin-mediated glucose uptake: 5.14±0.28 versus 7.26±0.61 mg glucose/kg fat-free mass per minute, hypertensive versus normotensive, P =.002), increased insulin levels during the insulin infusions (804±36 versus 510±38 pmol/L, hypertensive versus normotensive, P <.001), and decreased insulin metabolic clearance rate (328±15 versus 521±30 mL/min per meter squared, hypertensive versus normotensive, P <.001). In an ANCOVA (including sex, degree of obesity, waist-to-hip ratio, and insulin sensitivity as covariates) the differences in insulin metabolic clearance rate between normotensive and hypertensive subjects remained highly significant ( P <.001). Insulin metabolic clearance rate was significantly associated with fasting insulin levels. We conclude that essential hypertension is independently associated with decreased insulin metabolic clearance rate in addition to insulin resistance. A low insulin metabolic clearance rate may be a contributory factor to the hyperinsulinemia observed in essential hypertension.