Non-alcoholic fatty liver disease in obese subjects as related to increasing insulin resistance and deteriorating glucose control: Three years of follow-up from a longitudinal survey.

PURPOSE: This observational trial was performed to evaluate liver parameters in overweight or obese subjects in the context of insulin resistance and glucose control over time. SUBJECTS/METHODS: Insulin resistance, glucose control and several parameters for liver integrity were monitored in 177 overweight (BMI > 28 kg/m2) subjects over a mean of 30 months. Volunteers were categorized according to insulin resistance (HOMA(IR) score) and glucose control in subjects with normal glucose control (NGT), impaired glucose control (IGT), or diabetes mellitus type 2 (T2DM). Liver fat and fibrosis were evaluated by sonographic elastography (FibroScan®) and clinical scores, such as the AST/ALT ratio, fatty liver index (FLI), and NAFLD fibrosis score (NFS). RESULTS: Liver fat fraction as estimated by the controlled attenuation parameter (CAP), and the FLI were significantly higher in subjects with T2DM compared to IGT and NGT. While fasting insulin levels and the HOMA(IR) score continuously increased over time, no change in CAP or FLI occurred during follow up. CAP was correlated with FLI (r = 0.50; p < 0.0001) and the HOMA(IR) score (r = 0.32; p < 0.0001). An inverse correlation was observed between serum adiponectin levels and FLI (r = -0.37; p < 0.0001), the HOMA(IR) score (r = -0.19; p < 0.001, and CAP (r = -0.15; p < 0.01). CONCLUSIONS: In subjects with a BMI ≥ 28 kg/m(2), liver fat fraction is significantly elevated in those with T2DM compared to IGT or NGT. Liver fat fraction is associated with deteriorating insulin sensitivity and loss of glucose control. Despite a continuous increase in insulin resistance, no change in liver fat content or stiffness occurred over 30 months.