Association between diabetes, family history of diabetes,... : Hepatology (original) (raw)

Steatohepatitis/Metabolic Liver Disease

Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis

Loomba, Rohit1,2,*3; Abraham, Maria3; Unalp, Aynur3; Wilson, Laura3; Lavine, Joel4; Doo, Ed5; Bass, Nathan M.6 the Nonalcoholic Steatohepatitis Clinical Research Network

1_Division of Gastroenterology, Department of Medicine, and Preventive Medicine, University of California San Diego, La Jolla, CA_

2_Division of Epidemiology, Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA_

3_Johns Hopkins Bloomberg School of Public Health, Baltimore, MD_

4_Division of Pediatric Gastroenterology, Columbia University, New York, NY_

5_Liver Disease Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD_

6_Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, CA_

*Address reprint requests to: Division of Gastroenterology and Epidemiology, University of California at San Diego School of Medicine, UC 303, MC-0063, 9500 Gilman Drive, La Jolla, CA 92093

Email:[email protected]

Received 7 November 2011; Accepted 22 March 2012

Grant sponsor: American Gastroenterological Association (AGA) Foundation–Sucampo–Association of Specialty Professors Designated Research Award in Geriatric Gastroenterology and by a T. Franklin Williams Scholarship Award; Grant sponsor: Atlantic Philanthropies, Inc.; Grant sponsor: John A. Hartford Foundation; Grant sponsor: Association of Specialty Professors; Grant sponsor: AGA; Grant Number: K23DK090303; Grant sponsor: UCSD Digestive Diseases Research Development Center (U.S. PHS); Grant Number: DK080506; Grant sponsor: Nonalcoholic Steatohepatitis Clinical Research Network; Grant sponsor: National Institute of Diabetes and Digestive and Kidney Diseases; Grant Numbers: U01DK061718 U01DK061728 U01DK061731 U01DK061732 U01DK061734 U01DK061737 U01DK061738 U01DK061730 U01DK061713; Grant sponsor: National Institute of Child Health and Human Development.

Potential conflict of interest: Nothing to report.

The study was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. As per the policy of the network, the manuscript for this article was reviewed by the NIDDK before publication. The authors take complete responsibility of the data analyses and credibility of findings.

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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/m2, 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.