ESSENTIAL-HYPERTENSION IS ASSOCIATED WITH DECREASED INSULIN-CLEARANCEAND INSULIN-RESISTANCE

Essential hypertension is associated with multiple metabolic abnormali ties, among them, hyperinsulinemia. This hyperinsulinemia is attribute d to the presence of decreased insulin sensitivity (insulin resistance ) with consequent compensatory insulin secretion. We tested the hypoth esis that decreased insulin clearance is present in hypertensive subje cts and contributes to hyperinsulinemia independently of the degree of insulin resistance. Seventy-five subjects were studied (48 hypertensi ve and 27 normotensive). Both groups were comparable in terms of age, body fat content, waist-to-hip ratio, and sex distribution. A primed c ontinuous insulin infusion at 40 mU/m(2) per minute was performed. Glu cose was maintained at baseline levels with the euglycemic clamp techn ique. Hypertensive subjects were characterized by decreased insulin se nsitivity (insulin-mediated glucose uptake: 5.14+/-0.28 versus 7.26+/- 0.61 mg glucose/kg fat-free mass per minute, hypertensive versus normo tensive, P=.002), increased insulin levels during the insulin infusion s (804+/-36 versus 510+/-38 pmol/L, hypertensive versus normotensive, P<.001), and decreased insulin metabolic clearance rate (328+/-15 vers us 521+/-30 mL/min per meter squared, hypertensive versus normotensive , P<.001). In an ANCOVA (including sex, degree of obesity, waist-to-hi p ratio, and insulin sensitivity as covariates) the differences in ins ulin metabolic clearance rate between normotensive and hypertensive su bjects remained highly significant (P<.001). Insulin metabolic clearan ce rate was significantly associated with fasting insulin levels. We c onclude that essential hypertension is independently associated with d ecreased insulin metabolic clearance rate in addition to insulin resis tance. A low insulin metabolic clearance rate may be a contributory fa ctor to the hyperinsulinemia observed in essential hypertension.