Hepatic Fat in Participants With and Without Incident Diabetes in the Diabetes Prevention Program Outcome Study.

PURPOSE To characterize hepatic fat content and fatty liver prevalence, their determinants, and effect of interventions to prevent diabetes using computerized tomography in a cohort with prediabetes, in those developing diabetes versus not. METHODS We measured liver fat as liver attenuation (LA) in Hounsfield units in 1876 participants at ~14 years following randomization into the Diabetes Prevention Program, which tested the effects of lifestyle or metformin interventions versus standard care to prevent diabetes. LA was compared among intervention groups and in those with versus without diabetes, and associations with baseline and follow-up measurements of anthropometric and metabolic covariates were assessed. RESULTS There were no differences in liver fat between treatment groups at 14 years of follow-up. Participants with diabetes had lower LA (mean ± SD: 46±16 vs. 51±14HU; p<0.001) and a greater prevalence of fatty liver (LA<40HU) (34% vs 17%; p<0.001). Severity of metabolic abnormalities at the time of LA evaluation were associated with lower LA categories in a graded manner and more strongly in those with diabetes. Averaged annual fasting insulin (an index of insulin resistance [OR, 95% CI 1.76, 1.41-2.20]) waist circumference (1.63, 1.17-2.26), and triglyceride (1.42, 1.13-1.78), but not glucose, were independently associated with LA<40HU prevalence. CONCLUSIONS Fatty liver is common in the early phases of diabetes development. The association of LA with insulin resistance, waist circumference and triglyceride levels emphasizes the importance of these markers for hepatic steatosis in this population and that assessment of hepatic fat in early diabetes development is warranted.