Gastroenterology

Gastroenterology

Volume 126, Issue 2, February 2004, Pages 460-468
Gastroenterology

Clinical-liver, pancreas, and biliary tract
Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma

https://doi.org/10.1053/j.gastro.2003.10.065Get rights and content

Abstract

Background & Aims: An association between diabetes and chronic liver disease has been reported. However, the temporal relationship between these conditions remains unknown. Methods: We identified all patients with a hospital discharge diagnosis of diabetes between 1985 and 1990 using the computerized records of the Department of Veterans Affairs. We randomly assigned 3 patients without diabetes for every patient with diabetes. We excluded patients with concomitant liver disease. The remaining cohort was followed through 2000 for the occurrence of chronic nonalcoholic liver disease (CNLD) and hepatocellular carcinoma (HCC). Hazard rate ratios (HRR) were determined in Cox proportional hazard survival analysis. Results: The study cohort comprised 173,643 patients with diabetes and 650,620 patients without diabetes. Most were men (98%). Patients with diabetes were older (62 vs. 54 years) than patients without diabetes. The incidence of chronic nonalcoholic liver disease was significantly higher among patients with diabetes (incidence rate: 18.13 vs. 9.55 per 10,000 person-years, respectively, P < 0.0001). Similar results were obtained for HCC (incidence rate: 2.39 vs. 0.87 per 10,000 person-years, respectively, P < 0.0001). Diabetes was associated with an HRR of 1.98 (95% CI: 1.88 to 2.09, P < 0.0001) of CNLD and an HRR of 2.16 (1.86 to 2.52, P < 0.0001) of hepatocellular carcinoma. Diabetes carried the highest risk among patients with longer than 10 years of follow-up. Conclusions: Among men with diabetes, the risk of CNLD and HCC is doubled. This increase in risk is independent of alcoholic liver disease, viral hepatitis, or demographic features.

Section snippets

Databases

The study population was assembled from hospitalized veterans registered within the nationwide Patient Treatment File. The Patient Treatment File comprises a multitude of annual data files of which the main files contain discharge diagnoses recorded for each hospitalization since 1970. Individual patients can be traced through the annual files of the Patient Treatment File through their unique social security numbers. Each hospitalization record contains 1 primary discharge diagnosis and up to

Results

We identified 257,649 patients with diabetes and 772,947 patients without diabetes who were hospitalized in VA facilities between October 1985 and October 1990. Of these, 216,831 patients with diabetes and 765,853 patients without diabetes did not have liver disease in their hospitalization records as far back as 1980. After excluding all patients in whom liver disease was recorded during the first year of follow-up after the index hospitalization, 173,643 patients with diabetes and 650,620

Discussion

In this large prospective cohort study, we found that DM doubled the risk of CNLD as well as HCC. A causal relationship is further suggested by finding a temporal association in which diabetes preceded the diagnosis of CNLD and HCC and a significant duration-response in which the risk of these conditions with diabetes was highest among patients with more than 10 years of follow-up during the study. The increased risk was not explained by the presence of underlying liver disease or concomitant

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    1

    Dr. El-Serag is a VA HSR&D Awardee (RCD00-013-2).

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