c-peptide and Liver-Diseases--Alcoholic

In patients with non-insulin dependent diabetes mellitus (T2DM) and associated chronic liver disease, plasma levels of glucose, insulin and triglycerides are high, lipid peroxidation is increased and natural antioxidant reserves are reduced. Thus, we hypothesised that the re-balancing of cell redox levels and amelioration of liver function could result in a better glucose and lipid metabolism. To study this, we assessed the effect of a new oral formulation of an antioxidant agent - silybin-beta-cyclodextrin (named IBI/S) - in patients with chronic alcoholic liver disease and concomitant T2DM.. Sixty outpatients were enrolled in a three-centre, double blind, randomised, IBI/S vs placebo study. Forty-two (21 in the group IBI/S - 135 mg/d silybin per os - and 21 in the placebo group) concluded the 6-month treatment period. The efficacy parameters included fasting and mean daily plasma glucose levels, glycosylated hemoglobin (HbA1c), basal, stimulated C-peptide and insulin levels, total-, HDL-cholesterol and triglycerides levels in addition to conventional liver function tests. Insulin sensitivity was estimated by HOMA-IR. Malondialdehyde (MDA) was also measured before and after treatment as an index of oxidative stress.. Fasting blood glucose levels, which were similar at baseline in IBI/S group and in the placebo group (173.9 mg/dl and 177.1 mg/dl, respectively), decreased to 148.4 mg/dl (-14.7% vs baseline; p = 0.03) in the IBI/S group while they were virtually unchanged in the placebo group. The comparison between the groups at mo 6 (T6) also showed a significant reduction of glucose levels in the IBI/S group (p = 0.03). The same trend was observed in mean daily blood glucose levels, HbA1c and HOMA-IR, although differences were not significant. Basal and stimulated C-peptide values showed that only a few changes had occured in both groups. Such results indicate that insulin secretion was virtually unaffected, as confirmed also by the insulinemia data. Plasma triglycerides concentrations dropped from a baseline value of 186 mg/dl to 111 mg/dl (T6) in the IBI/S group, with significant differences at all instances with respect to baseline values. By contrast, triglycerides increased from 159 mg/dl at entry to 185 mg/dl (T6) in the placebo group. The difference between the groups at T6 was highly significant (p < 0.01). Total and HDL cholesterol as well as liver function tests did not change significantly during the study in both groups. MDA decreased significantly only in the group receiving IBI/S. No clinically relevant side effects were observed in either group.. Oral administration silybin-beta-cyclodextrin in patients with T2DM and compensated chronic alcoholic liver disease causes a significant decrease in both glucose and triglyceride plasma levels. These effects may be due to the recovery of energy substrates, consistent with a reduced lipid peroxidation and an improved insulin activity.

Topics: Antioxidants; beta-Cyclodextrins; Blood Glucose; C-Peptide; Cholesterol, HDL; Cyclodextrins; Diabetes Mellitus, Type 2; Double-Blind Method; Female; gamma-Glutamyltransferase; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Liver Diseases, Alcoholic; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Placebos; Silybin; Silymarin; Triglycerides

The results of puncture biopsy of the liver, ultrasonic and angiographic investigation of the liver and pancreas in 114 patients with chronic alcoholism revealed an increment of changes in these organs in parallel with an increase in the duration of chronic alcoholic intoxication. A simultaneous study of immunoreactive insulin (IRI) and C-peptide showed that an increase in the IRI basal level in the patients suffering from alcoholism up to 10 yrs was determined mainly by an increase in the activity of beta-cells. In a long period of alcoholism an increase in the IRI basal level resulted from a decrease in the rate of insulin degradation in the liver as assessed by a lower level of C-peptide. In liver cirrhosis a noticeable decrease in pancreatic incretory function was combined with noticeable disturbance of insulin degradation in the liver. The above investigations showed that there were morphological, functional and clinical signs of the "hepatopancreatic syndrome" in chronic alcoholism.

Topics: Adult; Alcoholism; C-Peptide; Glucose Tolerance Test; Humans; Insulin; Liver Diseases, Alcoholic; Male; Middle Aged; Pancreatic Diseases; Syndrome; Time Factors

In order to investigate disturbances in glycoregulation and plasma amino acids and their possible relationship in alcoholic liver diseases, plasma concentrations of insulin, C-peptide, glucagon and branched-chain (valine, leucine, isoleucine) as well as aromatic (phenylalanine, tyrosine) amino acids were measured during an arginine test (i.v infusion of arginine chloride 0.5 g/kg over 30 min) in 21 alcoholic patients: 11 with cirrhosis (group C) and 10 with steatosis (group S). Insulin responses to arginine was reduced in both groups, whereas glucagon response was increased in group C and reduced in group S. Plasma concentrations of branched-chain amino acids were reduced in both groups, irrespective of the degree of hyperinsulinism. Plasma concentrations of aromatic amino acids were increased only in cirrhotic patients; the increase was independent of the degree of hyperglucagonism and of the plasma insulin/glucagon molar ratio. These results suggest that disturbances of glycoregulation in plasma amino acids imbalance do not play a major role in alcoholic cirrhosis and steatosis.

Topics: Adult; Amino Acids; Arginine; Blood Glucose; C-Peptide; Fatty Liver, Alcoholic; Female; Glucagon; Humans; Insulin; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Male; Middle Aged

Changes in blood glucose and insulin metabolism, both under basal conditions and after glucose and glucagon stimulus, were studied in 95 patients with chronic alcoholic hepatopathy. Peptide C was also determined in 19 patients. A high incidence of islet-cell insufficiency was noted. Stress is laid on the multiplicity of the pathogenetic mechanisms responsible for blood glucose and insulin changes during chronic alcoholic hepatopathy, particularly liver cell damage, hyperglucagonaemia, organic and/or functional islet-cell insufficiency, and peripheral insulin resistance. It is felt that the last two of these are of major importance, whereas liver cell damage is of secondary significance, at any rate as far as glucose and insulin turnover is concerned.

Topics: C-Peptide; Fatty Liver, Alcoholic; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Male; Middle Aged