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Effect of metabolic components on incident type 2 diabetes mellitus in non‐alcoholic fatty liver disease subjects

To the Editor: With great interest, I read the article titled ‘The impact of non-alcoholic fatty liver disease on incident type 2 diabetes mellitus in non-overweight individuals’ by Fukuda et al. (1) The authors reported that nonoverweight participants with non-alcoholic fatty liver disease (NAFLD) might have a greater risk of type 2 diabetes mellitus (T2DM) than overweight participants without NAFLD in Japan. However, there were some issues that deserve further comments in assessing this relationship. First, I suggest that the effect of NAFLD on the incident T2DM in non-overweight participants may potentially be related to abnormal metabolic components. Non-alcoholic fatty liver disease is regarded as the hepatic component of metabolic syndrome or the precursor of metabolic syndrome (2). Increased waist circumference, elevated triglyceride and fasting plasma glucose levels, reduced high-density lipoprotein cholesterol levels and elevated blood pressure have frequently been found to be associated with NAFLD. A previous study (3) demonstrated that ‘metabolically unhealthy non-overweight’ people exhibited an increased risk of diabetes compared with ‘metabolically healthy overweight’ people. The term ‘metabolically unhealthy’ is similar to the status of NAFLD in Fukuda’s study, which is why these two studies reached similar results. Thus, these putative mediators should be considered potential covariates when performing the analysis. In addition, determining the role of these metabolic abnormalities may provide additional information about strategies used to prevent T2DM in individuals with NAFLD. Second, the study used body mass index (BMI) as an index of being overweight. However, participants with abdominal obesity (also known as central adiposity), independent of BMI, have been reported to have an increased risk for T2DM (4). Waist circumference (WC) is a more powerful predictor of diabetes than BMI (5). Although Fukuda et al. (1) reported that data of waist circumference were not available in their study, we still have to emphasize the importance of WC in predicting diabetes, particularly in participants with NAFLD. Thus, further studies are required to address this issue. Given the increasing prevalence of NAFLD, these additional clues may more precisely identify populations with NAFLD that should be targeted for therapeutic intervention to reduce T2DM incidence.