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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/E225    most recent 90960.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gastaldelli, A. Articles by Ferrannini, E. Search for Related Content PubMed PubMed Citation Articles by Gastaldelli, A. Articles by Ferrannini, E.

Decreased whole body lipolysis as a mechanism of the lipid-lowering effect of pioglitazone in type 2 diabetic patients

Fondazione G. Monasterio, Consiglio Nazionale delle Ricerca Institute of Clinical Physiology, and Department of Internal Medicine, Metabolism Unit, University of Pisa School of Medicine, Pisa, Italy

Submitted 28 November 2008 ; accepted in final form 5 May 2009

Pioglitazone has been shown to reduce fasting triglyceride levels. The mechanisms of this effect have not been fully elucidated, but decreased lipolysis may contribute to blunt the hypertriglyceridemic response to a meal. To test this hypothesis, we studied 27 type 2 diabetes mellitus (T2DM) patients and 7 sex-, age-, and body mass index-matched nondiabetic controls. Patients were randomized to pioglitazone (45 mg/day) or placebo for 16 wk. Whole body lipolysis was measured [as the [²H₅]glycerol rate of appearance (R_a)] in the fasting state and for 6 h following a mixed meal. Compared with controls, T2DM had higher postprandial profiles of plasma triglycerides, free fatty acid (FFA), and β-hydroxybutyrate, and a decreased suppression of glycerol R_a (P < 0.04) despite higher insulin levels [268 (156) vs. 190 (123) pmol/l, median (interquartile range)]. Following pioglitazone, triglycerides and FFA were reduced (P = 0.05 and P < 0.04, respectively), and glycerol R_a was more suppressed [–40 (137) vs. +7 (202) µmol/min of placebo, P < 0.05] despite a greater fall in insulin [–85 (176) vs. –20 (58) pmol/l, P = 0.05]. We conclude that, in well-controlled T2DM patients, whole body lipolysis is insulin resistant, and pioglitazone improves the insulin sensitivity of lipolysis.

insulin resistance; dyslipidemia; type 2 diabetes; thiazolidinediones