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What are the Risk Factors for Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes?

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Persons with type 2 diabetes have a more than 2-fold increase in risk for severe liver disease, researchers report in the December issue of Clinical Gastroenterology and Hepatology. The authors found risk factors that might be used to identify persons with type 2 diabetes who should be screened for liver disease.

(A) Cumulative incidence curve for severe liver disease. Patients with T2DM compared with controls. (B) Cumulative incidence curve for HCC and death in liver disease. Patients with T2DM compared with controls. HCC, hepatocellular carcinoma; T2DM, type 2 diabetes mellitus.

The burdens of obesity, type 2 diabetes, and liver diseases have increased significantly in the past decades, associated with an increasing prevalence of nonalcoholic fatty liver disease (NAFLD)—now estimated to affect nearly 25% of adults worldwide. As many as 70% of persons with type 2 diabetes are estimated to have fatty liver. Studies have reported an increased risk for significant liver disease, including hepatocellular carcinoma (HCC), in persons with type 2 diabetes. However, these studies had short follow-up periods, selection bias, and few data on risk factors for severe liver disease in persons with diabetes.

Guidelines recommend that persons with obesity, type 2 diabetes, or other metabolic risk factors should be regularly screened for NAFLD. The worldwide prevalence of type 2 diabetes is estimated at about 8%. We need more information on risk factors for liver disease in these persons; high-risk groups might be screened for liver fibrosis or asymptomatic cirrhosis.

Karl Björkström et al compared the risk for severe liver disease in an unbiased large, population-based cohort of persons with type 2 diabetes (n=406,770) vs a population without diabetes (2,033,850 controls) and identified risk factors associated with the development of clinically significant liver disease, including HCC.

During a median follow-up period of 7.7 years, 5092 persons with diabetes (1.3%) and 11,619 controls (0.6%) developed severe liver disease; 1071 persons with type 2 diabetes (0.26%) developed HCC vs 1671 controls (0.08%). Persons with type 2 diabetes had a more than 3-fold increase in risk of HCC compared to persons without diabetes.

Death from liver disease occurred in 1981 persons with type 2 diabetes (0.5%) vs 4549 controls (0.2%). Liver transplantation was performed in 87 persons with type 2 diabetes (0.02%) and 182 controls (0.009%).

See the figure for cumulative incidence curves for the composite endpoint severe liver disease in persons with type 2 diabetes and controls and for HCC and death from liver disease.

Compared with controls, the risk for severe liver disease was increased in men (2.37-fold increase in risk) and women (2.15-fold increase in risk), and in all age groups. However, in persons younger than 50, the absolute risk was below 1% during the follow-up period.

In Cox regression models, older age, smoking, male sex, hypertension, higher body mass index, lower glomerular filtration rate, and microalbuminuria were independently associated with increased risk of developing severe liver disease. Statins, higher low-density lipoprotein, and female sex were independently associated with decreased risk of severe liver disease.

Older age, male sex, hypertension, body mass index, glomerular filtration rate, and smoking were associated with increased risk of HCC, whereas statin use was associated with reduced risk. Other studies have reported the protective effects of statins in persons with chronic liver disease.

For cumulative incidences of severe liver disease, HCC, and death in liver disease at 1, 5, 10, and 15 years, see this table.

Björkström et al propose that initiatives to identify persons for screening for subclinical cirrhosis or advanced fibrosis should consider these risk factors. Reducing adjustable risk factors, such as smoking and body weight, would likely reduce the risk of liver disease and death.

The strength of this study is the large size of the cohort, derived from a population-based register in Sweden, which reduces selection bias. The results should be generalizable to other white populations with type 2 diabetes. Limitations include lack of data on risk factors in the control population and the follow-up time of a median 7.7 years—liver fibrosis progresses slowly in patients with NAFLD.

Studies of other populations, with longer follow-up periods, are needed.

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Kristine Novak

Kristine Novak

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About The Author:

Dr. Kristine Novak

Dr. Kristine Novak

Dr. Kristine Novak is a science writer and editor based in San Francisco. She has extensive experience covering gastroenterology, hepatology, immunology, oncology, clinical, and biotechnology research discoveries.

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