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J Gastroenterol. 2009;44(10):1064-70. doi: 10.1007/s00535-009-0091-1. Epub 2009 Jun 17.

Multivariate analysis of risk factors for the development of type 2 diabetes in nonalcoholic fatty liver disease.

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Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.



Diabetes is present in patients with nonalcoholic fatty liver disease (NAFLD). The aim of this retrospective cohort study was to assess the cumulative development of type 2 diabetes and predictive factors for its development in Japanese patients with NAFLD.


A total of 6003 NAFLD patients diagnosed by ultrasonography were enrolled. The mean follow-up period was 4.9 years. An overnight (12 h) fasting blood sample or a casual blood sample was taken for routine analyses during follow up. The primary outcome was the development of type 2 diabetes. Evaluation was performed by using the Kaplan-Meier method and Cox proportional hazards analysis.


Of the 6003 NAFLD patients, 411 patients developed type 2 diabetes. The cumulative development rate of type 2 diabetes was 6.8% at the 5th year and 17.7% at the 10th year. Multivariate Cox proportional hazards analysis showed that type 2 diabetes development in patients with NAFLD occurred when patients had prediabetes status (hazard ratio 6.39; 95% confidence interval 5.00-8.18; P < 0.001), mean serum gamma-glutamyltransferase (GGT) level of more than 109 IU/l (hazard ratio 1.60; 95% confidence interval 1.22-2. 02; P < 0.001), mean serum triglyceride (TG) level of more than 150 mg/l (hazard ratio 1.28; 95% confidence interval 1.05-1.55; P = 0.020), and physical activity of less than 60 min per week (hazard ratio 1.60; 95% confidence interval 1.25-2.00; P < 0.001).


The improvement of prediabetes status and physical activity, and the normalization of mean GGT and TG levels during follow up are important to prevent the development of T2DM in patients with NAFLD.

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