title: Circulating adiponectin levels in type 2 diabetes mellitus patients with or without non-alcoholic fatty liver disease: Results of a small, open-label, randomized controlled intervention trial in a subgroup receiving short-term exenatide.
abstract: OBJECTIVE
  Diabetes mellitus type 2 (DMT2) and non-alcoholic fatty liver disease (NAFLD) are both characterized by decreased circulating adiponectin. Recently, glucagon-like peptide-1 receptor agonists have been shown to induce adiponectin's expression. However, their interaction on clinical grounds needs to be further elucidated.
  
  
  METHODS
  DMT2 patients with abnormal aminotransferases were screened for NAFLD and subjected to liver biopsy (group A, n=17). A subgroup of patients (n=110), after assessed for eligibility criteria, was blindly randomized to receive either 6-month exenatide supplementation on glargine insulin (group B) or intense, self-regulated, insulin therapy alone (group C).
  
  
  RESULTS
  Baseline patient characteristics: 49(38.6%) males, aged 63.1 ± 7.5 years-old, BMI 32.9 ± 4.9 kg/m(2), HbA1c 8.1 ± 1.2% (65 ± 14 mmol/mol), median ALT 23 U/L (range 5-126), AST 20 U/L (7-72). Group A had biopsy-proven NAFLD with a median Activity Score of 5 and fibrosis stage 3. Presence of NAFLD was accompanied by a significant decline in adiponectin (p<0.001), which was negatively correlated with the degree of ALT in all groups (Spearman's correlation, rs=-0.644, p<0.001). In the subgroup intervention trial, adiponectin was significantly raised in both groups B and C (t-Student for paired samples, p=0.001) by Δ=+24.2% (interquartile range 14.8-53.2%). This elevation was not associated with the type of intervention but with weight loss, glycemic control and reduction of C-reactive protein (one-way ANCOVA).
  
  
  CONCLUSIONS
  Supplementation of exenatide to glargine insulin compared to standard insulin was: (i) effective in inducing weight loss, (ii) non-inferior in lowering HbA1c and (iii) non-inferior in increasing circulating adiponectin. Higher adiponectin was associated with lower ALT, suggesting a hepato-protective role for this cytokine.
authors.affiliation: Medical Center of Diabetes Mellitus, 1st Department of Internal Medicine, "Papageorgiou" University Hospital of Thessaloniki, Greece; Hepatology Outpatients' Clinic, "Papageorgiou" University Hospital of Thessaloniki, Greece; 4th Department of Internal Medicine, Hippocration University Hospital of Thessaloniki, Greece. Electronic address: ssavidou@med.auth.gr.
authors.forename: Savvoula
authors.initials: S
authors.lastname: Savvidou
authors.affiliation: Medical Center of Diabetes Mellitus, 1st Department of Internal Medicine, "Papageorgiou" University Hospital of Thessaloniki, Greece.
authors.forename: Kyparissia
authors.initials: K
authors.lastname: Karatzidou
authors.affiliation: Medical Center of Diabetes Mellitus, 1st Department of Internal Medicine, "Papageorgiou" University Hospital of Thessaloniki, Greece.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Tsakiri
authors.affiliation: Hepatology Outpatients' Clinic, "Papageorgiou" University Hospital of Thessaloniki, Greece.
authors.forename: Asterios
authors.initials: A
authors.lastname: Gagalis
authors.affiliation: Department of Pathology, Medical School of Aristotle University of Thessaloniki, Greece.
authors.forename: Prodromos
authors.initials: P
authors.lastname: Hytiroglou
authors.affiliation: 4th Department of Internal Medicine, Hippocration University Hospital of Thessaloniki, Greece.
authors.forename: John
authors.initials: J
authors.lastname: Goulis
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000008:administration & dosage*; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000150:complications*; D010455:Peptides / Q000008:administration & dosage*; D011446:Prospective Studies; D014688:Venoms / Q000008:administration & dosage*
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D002097:C-Reactive Protein; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D010455:Peptides; D014688:Venoms; C499918:ADIPOQ protein, human
keywords: Adiponectin; Diabetes mellitus type 2; Exenatide; Glucagon-like peptide-1; Non-alcoholic fatty liver disease