Hyperinsulinemia in preascitic cirrhosis: effects on systemic and renal hemodynamics, sodium homeostasis, forearm blood flow, and sympathetic nervous activity

Hepatology. 1996 Mar;23(3):414-22. doi: 10.1053/jhep.1996.v23.pm0008617419.


Insulin has been shown to be vasodilatory and antinatriuretic and to stimulate sympathetic nervous activity independent of hypoglycemia in healthy normal subjects. It is hypothesized that hyperinsulinemia, which is commonly observed in cirrhosis, may in part be responsible for the systemic vasodilatation, sympathetic activation, and sodium retention in these patients. The aims of this study, in preascitic cirrhotics, were as follows: (1) to document baseline hyperinsulinemia and its effects on sodium handling, forearm and renal circulations, and sympathetic nervous activity; (2) to determine if pharmacological increases in plasma insulin levels would result in an exaggeration of these physiological effects. Seven male, nonobese, well-compensated, preascitic cirrhotic patients were studied, after being maintained on a 150 mmol sodium per day diet for 7 days, firstly at baseline level, followed by increasing doses of insulin from 10 to 1,200 mU/m2/min using the euglycemic clamp technique. Systemic and renal hemodynamics, urinary sodium excretion, plasma norepinephrine, and forearm blood flow (FBF) were measured at the end of baseline and each hyperinsulinemic period. Baseline measurements in the cirrhotics, when compared with our laboratory standards obtained from a comparable group of male healthy normals, showed significant hyperinsulinemia (P=.01), associated with significantly higher FBF (P=.02), and glomerular filtration rate (GFR) (P=.02), as well as significantly reduced urinary volume (P=.04) and fractional excretion of sodium (P=.04). Insulin infusions in the cirrhotics produced no further sodium retention, but further forearm vasodilatation occurred at doses > or = 10 mU/m2/min. In contrast, there was no further renal vasodilatation except at very high pharmacological levels of insulin together with an unchanged GFR, natriuresis, and diuresis. Hyperinsulinemia produced no significant effects on the sympathetic nervous activity. In conclusion, these results suggest that hyperinsulinemia may be implicated in the glomerular hyperfiltration and sodium retaining tendency of preascitic cirrhotic patients with glucose intolerance. The ability of the kidneys to escape from the sodium retaining effects may serve as an in-built physiological regulatory mechanism on sodium homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Ascites / etiology
  • Blood Glucose / metabolism
  • Diuresis
  • Forearm / blood supply*
  • Glomerular Filtration Rate
  • Glucose Clamp Technique
  • Hemodynamics*
  • Homeostasis*
  • Humans
  • Hyperinsulinism / etiology*
  • Hyperinsulinism / metabolism
  • Insulin / blood
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / physiopathology
  • Male
  • Middle Aged
  • Natriuresis
  • Norepinephrine / blood
  • Regional Blood Flow
  • Renal Circulation*
  • Sodium / metabolism*
  • Sympathetic Nervous System / physiopathology*
  • Vascular Resistance


  • Blood Glucose
  • Insulin
  • Sodium
  • Norepinephrine