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Summary Context Peroxisome proliferator-activated receptor gamma (PPAR-γ) 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.

Summary Objective Cross-sectional studies suggest that the fatty acid (FA) composition of phospholipids in skeletal muscle cell membrane may modulate insulin sensitivity in humans. We examined the impact of a hypocaloric low-fat dietary intervention on membrane FA composition and insulin sensitivity. Design Muscle membrane FA profiles were determined in muscle (vastus lateralis) biopsies from 21 obese subjects before and after 6 months of dietary restriction. Diet instructions emphasized low intake of FA of marine origin by recommending lean fish and prohibiting fatty fish and fish oil supplements. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). Results The mean weight loss was 5·1 kg (range −15·3 to +1·3 kg). BMI decreased from 36·5 to 34·9 kg/m2 (P = 0·003). Saturated FA (SFA) decreased 11% (P = 0·0001). Polyunsaturated FA (PUFA)n-6 increased 4% (P = 0·003). Long-chain PUFAn-3 increased 51% (P = 0·0001), mainly due to a 75% increase (P

Summary Objective To obtain a better understanding of the physiological aspects of glucose homeostasis in human immunodeficiency virus (HIV)-infected patients with lipodystrophy, we evaluated separately β-cell function and insulin sensitivity after an oral glucose load. Design β-Cell function was investigated during an oral glucose tolerance test (OGTT) (75 g, 180 min) in 16 lipodystrophic HIV-infected patients and in 15 age- and weight-matched nonlipodystrophic HIV-infected patients. All participants were sedentary Caucasian males, who were on highly active antiretroviral therapy with no history of diabetes mellitus or impaired glucose tolerance. Prehepatic insulin secretion rates were estimated by deconvolution of C-peptide concentrations. A composite measure of insulin sensitivity was derived from the OGTT. Results β-Cell secretory capacity (i.e. the rate of change in insulin secretion per unit change in glucose concentration) was similar in lipodystrophic and nonlipodystrophic patients (6·2 ± 1·0 mU kg−1 min−1 mg−1 dl vs. 5·4 ± 0·4, P > 0·4), but insulin sensitivity was reduced by 61% in lipodystrophic patients (P