Pioglitazone decreases fasting and postprandial endogenous glucose production in proportion to decrease in hepatic triglyceride content

OBJECTIVE\u2014Hepatic triglyceride is closely associated with hepatic insulin resistance and is known to be decreased by thiazolididinediones. We studied the effect of pioglitazone on hepatic triglyceride content and the consequent effect on postprandial endogenous glucose production (EGP) in type 2 diabetes. RESEARCH DESIGN AND METHODS\u2014Ten subjects with type 2 diabetes on sulfonylurea therapy were treated with pioglitazone (30 mg daily) for 16 weeks. EGP was measured using a dynamic isotopic methodology after a standard liquid test meal both before and after pioglitazone treatment. Liver and muscle triglyceride levels were measured by 1H magnetic resonance spectroscopy, and intra-abdominal fat content was measured by magnetic resonance imaging. RESULTS\u2014Pioglitazone treatment reduced mean plasma fasting glucose and mean peak postprandial glucose levels. Fasting EGP decreased after pioglitazone treatment (16.6 \ub1 1.0 vs. 12.2 \ub1 0.7 \u3bcmol \ub7 kg 121 \ub7 min 121, P = 0.005). Between 80 and 260 min postprandially, EGP was twofold lower on pioglitazone (2.58 \ub1 0.25 vs. 1.26 \ub1 0.30 \u3bcmol \ub7 kg 121 \ub7 min 121, P < 0.001). Hepatic triglyceride content decreased by 3c50% (P = 0.03), and muscle (anterior tibialis) triglyceride content decreased by 3c55% (P = 0.02). Hepatic triglyceride content was directly correlated with fasting EGP (r = 0.64, P = 0.01) and inversely correlated to percentage suppression of EGP (time 150 min, r = 120.63, P = 0.02). Muscle triglyceride, subcutaneous fat, and visceral fat content were not related to EGP. CONCLUSIONS\u2014Reduction in hepatic triglyceride by pioglitazone is very closely related to improvement in fasting and postprandial EGP in type 2 diabetes