INSULIN-RESISTANCE IN MICROALBUMINURIC HYPERTENSION - SITES AND MECHANISMS

Microalbuminuria in patients with essential hyper tension is a marker of incipient glomerular dysfunction and clusters with lipid and hemodynamic abnormalities. Recent evidence has shown that hypertensive patients with microalbuminuria have a hyperinsulinemic response to oral glucose, suggesting the presence of insulin resistance. To directly test this possibility we studied insulin action in two accurately matched groups (n=10 each) of hypertensive patients with or without microalbuminuria (14+/-2 versus 52+/-7 mg . 24 h(-1), mean of three 24-hour collections). In response to glucose ingestion microalbuminuric patients showed slight hyperglycemia (area under the curve, 928+/-43 versus 784=/-19 mmol . L(-1). 2 h(-1), P<.02) and a marked hyperinsulinemia (26.8+/-3.3 versus 49.8+/-3.7 nmol L(-1). 2 h(-1), P<.001). Basal arterial blood pressure, heart rate, and forearm blood flow were similar in the two groups and did not change significantly during a 2-hour euglycemic insulin clamp. Insulin-stimulated whole-body glucose uptake was 25% lower in microalbuminuric patients (33.5+/-2.5 versus 25.2+/-2.1 mu mol . min(-1). kg(-1), P<.02). This difference was entirely due to a 40% reduction in glycogen synthesis (12.9+/-1.8 versus 21.3+/-3.2 mu mol . min(-1). kg(-1), P<.05) as glucose oxidation was similarly stimulated in the two groups. In contrast, there was no difference in the ability of insulin to suppress hepatic glucose production (by approximately 100% at the end of the clamp), to decrease fractional sodium and potassium excretions (by 35%), to lower circulating free fatty acids (by 80%), and to reduce plasma potassium concentrations (by 10%). Insulin sensitivity was inversely related to albumin excretion rate even after adjustment for body mass index (partial r=.51, P<.03). When both insulin sensitivity and the insulin area under the curve were entered into a multiple regression equation, the insulin area was more strongly related to albumin excretion and, together with 24-hour mean blood pressure, explained approximately 60% of its variability (P<.001). In conclusion, microalbumin uria in essential hypertension signals the presence of a selective impairment in peripheral insulin-mediated glucose uptake and an enhanced insulin secretory response to glucose. Insulin levels rather than insulin sensitivity appear to be related to urinary albumin excretion.