HYPERINSULINEMIA IN PREASCITIC CIRRHOSIS - EFFECTS ON SYSTEMIC AND RENAL HEMODYNAMICS, SODIUM HOMEOSTASIS, FOREARM BLOOD-FLOW, AND SYMPATHETIC NERVOUS ACTIVITY

Insulin has been shown to be vasodilatory and antinatriuretic and to s timulate sympathetic nervous activity independent of hypoglycemia in h ealthy normal subjects. It is hypothesized that hyperinsulinemia, whic h is commonly observed in cirrhosis, may in part be responsible for th e systemic vasodilatation, sympathetic activation, and sodium retentio n in these patients. The aims of this study, in preascitic cirrhotics, were as follows: (1) to document baseline hyperinsulinemia and its ef fects on sodium handling, forearm and renal circulations, and sympathe tic nervous activity; (2) to determine if pharmacological increases in plasma insulin levels would result in an exaggeration of these physio logical effects. Seven male, nonobese, well-compensated, preascitic ci rrhotic patients were studied, after being maintained on a 150 mmol so dium per day diet for 7 days, firstly at baseline level, followed by i ncreasing doses of insulin fi om 10 to 1,200 mU/m(2)/min using the eug lycemic clamp technique. Systemic and renal hemodynamics, urinary sodi um excretion, plasma norepinephrine, and forearm blood flow (FBF) were measured at the end of baseline and each hyperinsulinemic period. Bas eline measurements in the cirrhotics, when compared with our laborator y standards obtained from a comparable group of male healthy normals, showed significant hyperinsulinemia (P = .01), associated with signifi cantly higher FBF (P = .02), and glomerular filtration rate (GFR) (P = .02), as well as significantly reduced urinary volume (P = .04) and f ractional excretion of sodium (P = .04). Insulin infusions in the cirr hotics produced no further sodium retention, but further forearm vasod ilatation occurred at doses greater than or equal to 10 mU/m(2)/min. I n contrast, there was no further renal vasodilatation except at very h igh pharmacological levels of insulin together with an unchanged GFR, natriuresis, and diuresis. Hyperinsulinemia produced no significant ef fects on the sympathetic nervous activity. In conclusion, these result s suggest that hyperinsulinemia may be implicated in the glomerular hy perfiltration and sodium retaining tendency of preascitic cirrhotic pa tients with glucose intolerance. The ability of the kidneys to escape from the sodium retaining effects may serve as an in-built physiologic al regulatory mechanism on sodium homeostasis.