Hepatic Fat in Participants with and without Incident Diabetes in the Diabetes Prevention Program Outcome Study

Context: There is little information about fatty liver in prediabetes as it transitions to early diabetes. Objective: This study is aimed at evaluating the prevalence and determinants of fatty liver in the Diabetes Prevention Program (DPP). Methods: We measured liver fat as liver attenuation (LA) in Hounsfield units (HU) in 1876 participants at ∼14 years following randomization into the DPP, 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 ± 14 HU; P < 0.001) and a greater prevalence of fatty liver (LA < 40 HU) (34% vs 17%; P < 0.001). Severity of metabolic abnormalities at the time of LA evaluation was 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 < 40 HU prevalence. Conclusion: 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.