Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes

Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 +/- A 1.7 years, HbA1c 8.7 +/- A 0.2 %, body mass index 24.5 +/- A 0.5 kg/m(2)) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor alpha (TNF alpha) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Delta = -68 %, insulin Delta = -58 %, pioglitazone Delta = -49 %). Exenatide reduced VF (Delta = -36 %) and SF (Delta = -13 %), and pioglitazone decreased VF (Delta = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNF alpha (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that Delta IHF correlated with Delta HbA1c and Delta weight. Besides, Delta IHF correlated with Delta triglycerides and Delta TNF alpha, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, Delta HbA1c alone explained 41.5 % of the variance of Delta IHF, and Delta HbA1c + Delta weight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM.