title: Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis.
abstract: Previous studies have shown familial aggregation of insulin resistance and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to examine whether family history of diabetes mellitus (DM) is associated with nonalcoholic steatohepatitis (NASH) and fibrosis in patients with NAFLD. This was a cross-sectional analysis in participants of the NAFLD Database study and PIVENS trial who had available data on family history of DM. One thousand and sixty-nine patients (63% women), with mean age of 49.6 (± 11.8) years and body mass index (BMI) of 34.2 (± 6.4) kg/m(2) , were included. Thirty percent had DM, and 56% had a family history of DM. Both personal history of DM and family history of DM were significantly associated with NASH, with an odds ratio (OR) of 1.93 (95% confidence interval [CI]: 1.37-2.73; P <0.001) and 1.48 (95% CI: 1.11-1.97; P = 0.01) and any fibrosis with an OR of 3.31 (95% CI: 2.26-4.85; P < 0.001) and 1.66 (95% CI: 1.25-2.20; P < 0.001), respectively. When the models were adjusted for age, sex, BMI, ethnicity, and metabolic traits, the association between diabetes and family history of DM with NASH showed an increased adjusted OR of 1.76 (95% CI: 1.13-2.72; P < 0.001) and 1.34 (95% CI: 0.99-1.81; P = 0.06), respectively, and with any fibrosis with a significant adjusted OR of 2.57 (95% CI: 1.61-4.11; P < 0.0001) and 1.38 (95% CI: 1.02-1.87; P = 0.04), respectively. After excluding patients with personal history of diabetes, family history of DM was significantly associated with the presence of NASH and any fibrosis with an adjusted OR of 1.51 (95% CI: 1.01-2.25; P = 0.04) and 1.49 (95% CI: 1.01-2.20; P = 0.04), respectively.
  
  
  CONCLUSIONS
  Diabetes is strongly associated with risk of NASH, fibrosis, and advanced fibrosis. Family history of diabetes, especially among nondiabetics, is associated with NASH and fibrosis in NAFLD.
authors.affiliation: Division of Gastroenterology, Department of Medicine, and Preventive Medicine, University of California San Diego, La Jolla, CA 92093, USA. roloomba@ucsd.edu
authors.forename: Rohit
authors.initials: R
authors.lastname: Loomba
authors.forename: Maria
authors.initials: M
authors.lastname: Abraham
authors.forename: Aynur
authors.initials: A
authors.lastname: Unalp
authors.forename: Laura
authors.initials: L
authors.lastname: Wilson
authors.forename: Joel
authors.initials: J
authors.lastname: Lavine
authors.forename: Ed
authors.initials: E
authors.lastname: Doo
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Bass
mesh_terms: D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000150:complications* / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics*; D005234:Fatty Liver / Q000209:etiology*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D011446:Prospective Studies; D012307:Risk Factors