Does NAFLD mediate the relationship between obesity and type 2 diabetes risk? evidence from the multi-ethnic study of atherosclerosis (MESA).

ABSTRACT Purpose To estimate the effect of obesity on type 2 diabetes (T2DM) risk and evaluate to what extent non-alcoholic fatty liver disease (NAFLD) mediates this association. Methods Data came from 4,522 adults ages 45–84 participating in the Multi-Ethnic Study of Atherosclerosis cohort. Baseline obesity was defined using established BMI categories. NAFLD was measured by CT scans at baseline and incident T2DM defined as fasting glucose ≥126 mg/dL or use of diabetes medications. Results Over a median 9.1 years of follow-up between 2000 and 2012, 557 new cases of T2DM occurred. After adjusting for age, sex, race/ethnicity, education, diet and exercise, those with obesity had 4.5 times the risk of T2DM compared to normal weight (hazard ratio [HR] = 4.5, 95% confidence interval [CI]: 3.0, 5.9). The mediation analysis suggested that NAFLD accounted for ~36% (95% CI: 27, 44) of the effect (direct effect HR = 3.2, 95% CI: 2.3, 4.6; indirect effect through NAFLD, HR = 1.4, 95% CI: 1.3, 1.5). Conclusions These data suggest that the association between obesity and T2DM risk is partially explained by the presence of NAFLD. Future studies should evaluate if NAFLD could be an effective target to reduce the effect of obesity on T2DM.