Insulin resistance increases the risk of incident type 2 diabetes mellitus in patients with non‐alcoholic fatty liver disease

Background Type 2 diabetes mellitus (T2DM) is a major complication of patients with nonalcoholic fatty liver disease (NAFLD). The aim of this retrospective study is to determine the risk factor for development of T2DM in patients with biopsy proven NAFLD. Methods Consecutive 162 patients with biopsy-proven NAFLD patients who received 75g oral glucose tolerance test (OGTT) were enrolled as the total cohort. Among them, we analyzed 89 patients without T2DM diagnosed by OGTT to estimate the cumulative rate for development of T2DM as the follow-up cohort. Results Of 162 patients, the glucose tolerance pattern were DM in 45 patients (27.8%); impaired glucose tolerance in 68 (42.0%) and normal glucose tolerance in 49 (30.2%). Patients with nonalcoholic fatty liver (NAFL) tended to be more likely to have NGT than those with nonalcoholic steatohepatitis (NASH). The serum levels of pre- and post-load insulin were significantly higher in NASH group. Of 89 patients without T2DM, 13 patients newly developed T2DM during a follow-up period of 5.2 years. The cumulative rate of T2DM incidence was 8.8% at the end of the 5th year and 23.4% at the end of the 10th year. Multivariate analysis identified HOMA-IR (≥3.85, hazard ratio 40.1, p=0.033) as an independent risk factor for development of T2DM. Conclusions The NASH patients have underlying potential of glucose intolerance. In NAFLD patients, insulin resistance is the most important risk factor for the incidence of T2DM. The appropriate therapy against insulin resistance might be needed for patients with NAFLD to prevent development of T2DM. (word count: 250) Key words: insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, OGTT