title: Glucose disposal, beta-cell secretion, and hepatic insulin extraction in cirrhosis: a minimal model assessment.
abstract: Factors controlling glucose metabolism after IV load were studied in nine patients with compensated cirrhosis and in six age-matched controls. The time courses of glucose, insulin, and C peptide were analyzed by means of the minimal model technique. In cirrhosis, insulin sensitivity was reduced by approximately 70% and glucose-dependent glucose uptake (glucose effectiveness) by 45%. Decreased glucose effectiveness explained 65% of the variance of glucose disappearance and correlated with the ratio of urinary creatinine to height, an independent measure of muscle mass (r = 0.839). beta-cell responsiveness to glucose, measured on C-peptide kinetics, was variable and increased on average by 170% and 107% (first-phase and second-phase, respectively). The total amount of insulin secreted by beta-cells in the course of the study was nearly doubled, whereas the basal insulin secretion rate was in the normal range. The time courses of hepatic extraction of insulin did not differ between groups, and basal extraction was on average 58% in controls and 56% in patients with cirrhosis. It was reduced to 30% in a single patient who had severe hepatocellular failure and large spontaneous portosystemic shunting. We conclude that the alterations in glucose metabolism of cirrhosis include a decreased insulin sensitivity, a reduced glucose effectiveness, and an increased pancreatic responsiveness to glucose, leading to hyperinsulinemia. The hepatic extraction of insulin is reduced only in the very advanced stages of the disease, possibly because of a large reserve capacity of the hepatic parenchyma.
authors.affiliation: Instituto di Clinica Medica Generale e Terapia, Università di Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Marchesini
authors.forename: G
authors.initials: G
authors.lastname: Pacini
authors.forename: G
authors.initials: G
authors.lastname: Bianchi
authors.forename: D
authors.initials: D
authors.lastname: Patrono
authors.forename: C
authors.initials: C
authors.lastname: Cobelli
mesh_terms: D000328:Adult; D001682:Biological Availability; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007275:Injections, Intravenous; D007328:Insulin / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology; D007515:Islets of Langerhans / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D007328:Insulin; D005947:Glucose