(Hypertension. 1995;26:789.)
© 1995 American Heart Association, Inc.
Articles |
Insulin Resistance in Microalbuminuric Hypertension
Sites and Mechanisms
From the Nephrology Unit, Spedali Riuniti, Livorno (S.B., R.B.), and Metabolism Unit of the CNR Institute of Clinical Physiology, Pisa (A.Q.G., E.M., G.B., N.P., D.C., E.F., A.N.), Italy.
Correspondence to Dr Roberto Bigazzi, U.O. di Nefrologia, Spedali Riuniti, Viale Alfieri 36, 57100 Livorno, Italy.
Abstract Microalbuminuria in patients with essential hypertension 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 µmol · 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 µmol ·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, microalbuminuria 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.
Key Words: hypertension, essential • albuminuria • insulin resistance
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