Metabolically Healthy Obesity, Presence or Absence of Fatty Liver, and Risk of Type 2 Diabetes in Japanese Individuals: Toranomon Hospital Health Management Center Study 20 (TOPICS 20)

Objective: We investigated whether the metabolically healthy obese (MHO) phenotype was associated with an increased risk of the development of diabetes. If so, we aimed to determine what factors could explain this finding. Design, Setting, and Participants: Studied were 8090 Japanese individuals without diabetes. Metabolic health status was assessed by common clinical markers: blood pressure, triglycerides, high-density lipoprotein-cholesterol, and fasting glucose concentrations. The cutoff value for obesity or normal weight (NW) was a body mass index of 25.0 kg/m(2). Results: The 5-year incidence rate of diabetes was 1.2% (n = 58 of 4749) in metabolically healthy NW (MHNW) individuals, 2.8% (n = 20 of 719) in MHO individuals, 6.0% (n = 102 of 1709) in metabolically abnormalNWindividuals, and 10.3%(n = 94 of 913) in metabolically abnormal obese individuals. Although MHO individuals had no or one metabolic factor, 47.8% had ultrasonographic fatty liver (FL). The MHO group had a significantly increased risk of diabetes compared with the MHNW group [multivariate adjusted odds ratio (OR) 2.23 (95% confidence interval [CI] 1.33, 3.75)], but this risk was attenuated after adjustment for FL. Compared with the MHNW/non-FL group, the risk of diabetes in the MHO/non-FL group was not significantly elevated [OR 1.01 (95% CI 0.35, 2.88)]. However, the MHO/FL and MHNW/FL groups had similarly elevated risks of diabetes [OR 4.09 (95% CI 2.20, 7.60) and 3.16 (1.78, 5.62), respectively]. Conclusions: Almost half of the MHO participants had FL, which partially explained the increased risk of diabetes among the obese phenotypes. The presence of FL should be evaluated to assess whether an individual was actually in a metabolically benign state for the prediction of diabetes.