Scientific Contributions Elevated Serum Insulin Levels in Patients With Essential Hypertension and Microalbuminuria

Hyperinsulinemia, insulin resistance, or both have been described in patients with essential hypertension. Previous work from our laboratory has shown that in hypertensive patients with microalbuminuria, dyslipidemia and abnormal patterns in the diurnal variations of blood pressure are frequently associated. Whether hyperinsulinemia and microalbuminuria are directly related has not been determined. To test this possibility, we measured the plasma insulin response to an oral glucose load in 25 patients with or without microalbuminuria and 20 normotensive control subjects. Serum lipid profile and 24-hour ambulatory blood pressure were obtained. In the hypertensive patients as a group, the plasma insulin response to glucose (evaluated as the insulin area under the curve) was significantly enhanced compared with a group of 20 normotensive healthy control subjects (46 311+3745 and 27 557±2563 pmol/Lx2 hours, f<.01). When the hypertensive patients were subdivided according to their albumin excretion rate, the microalbuminuric patients had significantly higher plasma glucose Microalbuminuria, defined as urinary albumin excretion (UAE) exceeding 30 mg per 24 hours, is present in 35% to 40% of patients with essential hypertension and is associated with an unfavorable serum lipid profile and increased cardiovascular morbidity and mortality. Recent studies have indicated that microalbuminuria is a marker of glomerular damage; in patients with insulin-dependent diabetes mellitus (IDDM), it predicts the development of overt proteinuria and progressive renal failure. Although the predictive value of microalbuminuria in non-insulin-dependent diabetes mellitus (NIDDM) is less well established, in both NIDDM and IDDM patients microalbuminuria predicts cardiovascular morbidity and mortality. Treatment of hypertension retards the progression of microalbuminuria and renal disease in patients with IDDM. Evidence also indicates that microalbuminuria can be considered an early sign of renal damage in patients with essential hypertension.More recently, several investigators have described the presence of insulin resistance and hyperinsulinemia in a substantial number of patients with essential hyperReceived December 12,1993; accepted in revised form March 2, 1994. From the U.O. di Nefrologia, Spedali Riuniti, Livorno, Italy (S.B., R.B., C.V., I.C., G.S., G.B.), The Metabolism Unit, National Council of Research Institute of Clinical Physiology, University of Pisa (Italy) (A.N., E.F.), and the Division of Nephrology, University of Southern California, Los Angeles (V.M.C.). Correspondence to Vito M. Campese, MD, LAC/USC Medical Center, 2025 Zonal Ave, Los Angeles, CA 90033. (969±45.2 versus 762±28.7 mmol/Lx2 hours, P<.01) and insulin (59172+5964 versus 37 737±3422 pmol/Lx2 hours, P<.01) area under the curve values. In addition, a significant direct correlation was found to exist between insulin area under the curve and the urinary albumin excretion rate (r=.63, P<.001). Serum levels of lipoprotein(a) were significantly greater (P<.01) in patients with than in those without microalbuminuria and in control subjects. Furthermore, daytime diastolic blood pressure and nighttime systolic and diastolic blood pressure values were greater in patients with than in those without microalbuminuria. We conclude that in patients with essential hypertension microalbuminuria is associated with an enhanced insulin response to glucose, altered lipid levels, and an abnormal circadian blood pressure pattern, thereby forming a cluster with pathogenic potential for cardiovascular complications. (Hypertension. 1994;23[part l]:681-687.)