Peroxisome Proliferator-Activated Receptor Gamma Agonism Modifies The Effects Of Growth Hormone On Lipolysis And Insulin Sensitivity

Context Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists such as thiazolidinediones (TZDs) improve insulin sensitivity in type 2 diabetes mellitus (T2DM) through effects on fat metabolism whereas GH stimulates lipolysis and induces insulin resistance.Objective To evaluate the impact of TZDs on fat metabolism and insulin sensitivity in subjects exposed to stable GH levels.Design A randomized, placebo-controlled, double-blind parallel-group study including 20 GH-deficient patients on continued GH replacement therapy. The patients were studied before and after 12 weeks.Intervention Patients received either pioglitazone 30 mg (N = 10) or placebo (N = 10) once daily for 12 weeks.Results Adiponectin levels almost doubled during pioglitazone treatment (P = 0.0001). Pioglitazone significantly decreased basal free fatty acid (FFA) levels (P = 0.02) and lipid oxidation (P = 0.02). Basal glucose oxidation rate (P = 0.004) and insulin sensitivity (P = 0.03) improved in the patients who received pioglitazone treatment. The change in insulin-stimulated adiponectin level after pioglitazone treatment was positively correlated to the change in insulin-stimulated total glucose disposal (R = 0.69, P = 0.04).Conclusion The impact of GH on lipolysis and insulin sensitivity can be modified by administration of TZDs.