title: Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medical and Surgical Sciences, University of Padova, Italy. flavio.lirussi@unipd.it
authors.forename: F
authors.initials: F
authors.lastname: Lirussi
authors.forename: A
authors.initials: A
authors.lastname: Beccarello
authors.forename: G
authors.initials: G
authors.lastname: Zanette
authors.forename: A
authors.initials: A
authors.lastname: De Monte
authors.forename: V
authors.initials: V
authors.lastname: Donadon
authors.forename: M
authors.initials: M
authors.lastname: Velussi
authors.forename: G
authors.initials: G
authors.lastname: Crepaldi
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003505:Cyclodextrins / Q000008:administration & dosage / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008108:Liver Diseases, Alcoholic / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008875:Middle Aged; D018384:Oxidative Stress; D010919:Placebos; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood; D047392:beta-Cyclodextrins; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D002096:C-Peptide; D008076:Cholesterol, HDL; D003505:Cyclodextrins; D006442:Glycated Hemoglobin; D007328:Insulin; D008315:Malondialdehyde; D010919:Placebos; D000077385:Silybin; D012838:Silymarin; D014280:Triglycerides; D047392:beta-Cyclodextrins; D005723:gamma-Glutamyltransferase; C472368:silybin-beta-cyclodextrin