title: Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease.
abstract: OBJECTIVE
  To explore the association between hepatocellular carcinoma (HCC) and type 2 diabetes mellitus, describe the temporal relations between the onset of diabetes and the development of HCC and evaluate the possible effects of antidiabetic therapy on HCC risk.
  
  
  METHODS
  We recruited 465 HCC patients, 618 with cirrhosis and 490 control subjects. We evaluated the odds ratio (OR) for HCC by univariate and multivariate analysis. Moreover, OR for HCC in diabetic subjects treated with insulin or sulphanylureas and with metformin were calculated.
  
  
  RESULTS
  The prevalence of diabetes mellitus was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in the Control group. By univariate and multivariate analysis, the OR for HCC in diabetic patients were respectively 3.12 (CI 2.2-4.4, P < 0.001) and 2.2 (CI 1.2-4.4, P = 0.01). In 84.9% of cases, type 2 diabetes mellitus was present before the diagnosis of HCC. Moreover, we report an OR for HCC of 2.99 (CI 1.34-6.65, P = 0.007) in diabetic patients treated with insulin or sulphanylureas, and an OR of 0.33 (CI 0.1-0.7, P = 0.006) in diabetic patients treated with metformin.
  
  
  CONCLUSIONS
  Our study confirms that type 2 diabetes mellitus is an independent risk factor for HCC and pre-exists in the majority of HCC patients. Moreover, in male patients with type 2 diabetes mellitus, our data shows a direct association of HCC with insulin and sulphanylureas treatment and an inverse relationship with metformin therapy.
authors.affiliation: Department of Medicine, Internal Medicine 3rd, Pordenone Hospital, Pordenone, Italy. valter.donadon@aopn.fvg.it
authors.forename: Valter
authors.initials: V
authors.lastname: Donadon
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Balbi
authors.forename: Michela
authors.initials: M
authors.lastname: Ghersetti
authors.forename: Silvia
authors.initials: S
authors.lastname: Grazioli
authors.forename: Antonio
authors.initials: A
authors.lastname: Perciaccante
authors.forename: Giovanni
authors.initials: G
authors.lastname: Della Valentina
authors.forename: Rita
authors.initials: R
authors.lastname: Gardenal
authors.forename: Maria
authors.initials: M
authors.lastname: Dal Mas
authors.forename: Pietro
authors.initials: P
authors.lastname: Casarin
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zanette
authors.forename: Cesare
authors.initials: C
authors.lastname: Miranda
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use; D008107:Liver Diseases / Q000150:complications* / Q000209:etiology* / Q000503:physiopathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds