β-cell response and insulin hepatic extraction in noncirrhotic alcoholic patients soon after withdrawal

Abstract

A decreased tolerance to carbohydrates has been reported in several studies of liver diseases, whereas only a few investigations have been performed in chronic noncirrhotic alcoholic patients with and without alcohol abstinence. The aim of this study was to evaluate in detail the metabolic portrait of six noncirrhotic alcoholics during the early phase of alcohol withdrawal by quantifying the main processes involved in glucose disappearance. Data from frequently sampled intravenous glucose tolerance tests (FSIGTs) were analyzed by means of the minimal model (MINMOD) approach, which provided measurements of the (prehepatic) β-cell secretion and of insulin degradation in the liver, along with indexes of insulin sensitivity and glucose effectiveness. Plasma insulin levels were lower in the patients (basal, 3.5 ± 0.2 v 8.0 ± 1.8 in matching controls, P < .05; area under the curve; 1.41 ± 0.07 mU/mL in 240 minutes v 4.06 ± 0.37, P < .001), and C-peptide concentrations were higher (basal, 107 ± 3.5 v 36 ± 9 ng/dL in controls, P < .05; area under the curve, 492 ± 118 ng/mL in 240 minutes v 245 ± 66, P = .05). The model analysis confirmed the absence of a decrease β-cell release; in fact, in the alcoholics there was a basal secretion of 19 ± 5 versus 9 ± 2 pmol/L/min in controls ( P < .05) and a total release of 9.5 ± 1.8 nmol/L in 240 minutes versus 6.5 ± 1.4. The percent hepatic extraction was twice as high in the patients (79 ± 3 v 43 ± 5, P < .001); thus, the low peripheral insulin concentration of the alcoholics in the early phase of alcohol withdrawal was ascribed to an increased capacity of the liver to dispose of insulin, rather than to a decreased β-cell activity.