title: Diabetes as a risk factor for hepatic encephalopathy in cirrhosis patients.
abstract: OBJECTIVE
  It remains unclear whether diabetes increases the risk for hepatic encephalopathy (HE) in cirrhotic patients. We examined this question using data from three randomized trials of satavaptan, a vasopressin receptor antagonist that does not affect HE risk, in cirrhotic patients with ascites.
  
  
  METHODS
  The trials included 1198 patients, and we excluded those with HE before or at randomization and followed the remaining patients for the one year duration of the trials. They were examined for HE regularly, and we compared rates of first-time overt HE between diabetics and non-diabetic patients using Cox regression, adjusting for gender, age, ascites severity, cirrhosis etiology, Child-Pugh class, creatinine, bilirubin, INR, sodium, potassium, albumin, platelets, lactulose use, benzodiazepine/barbiturate use, spironolactone dose, furosemide dose, potassium-sparing diuretic dose, and CirCom comorbidity score.
  
  
  RESULTS
  We included 862 patients of whom 193 (22%) had diabetes. In total, they experienced 115 first-time episodes of overt HE during the follow-up. Fewer diabetics than non-diabetic patients were in Child-Pugh class C at baseline (13% vs. 23%), yet they had higher cumulative risk of first-time overt HE (26.0% vs. 15.8% after 1 year), and their episodes of first-time overt HE were more likely to progress beyond grade 2 (64% vs. 42% of episodes progressed to grade 3 or 4, p=0.01 for independence between diabetes and highest HE grade). After the confounder adjustment, the hazard ratio of first-time overt HE for diabetics vs. non-diabetic patients was 1.86 (95% CI 1.20-2.87).
  
  
  CONCLUSIONS
  Diabetes increased the risk of first-time overt HE among cirrhotic patients with ascites.
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: pj@clin.au.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Jepsen
authors.affiliation: Sanofi Aventis R&D, Paris, France.
authors.forename: Hugh
authors.initials: H
authors.lastname: Watson
authors.affiliation: Department of Biostatistics, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Per Kragh
authors.initials: PK
authors.lastname: Andersen
authors.affiliation: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage; D003920:Diabetes Mellitus / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005602:France / Q000453:epidemiology; D006501:Hepatic Encephalopathy / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications* / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013141:Spiro Compounds / Q000008:administration & dosage*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D009025:Morpholines; D013141:Spiro Compounds; C103281:satavaptan
keywords: Cirrhosis; Diabetes mellitus; End-stage liver disease; Hepatic encephalopathy; Prognosis