Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment

Objective: To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS). Design: The present study is a secondary analysis of a previously published case-control study, followed by a double-blind randomized clinical trial. Setting: Academic tertiary care medical center. Patient(s): Thirty obese premenopausal patients with PCOS and 14 healthy women. Intervention(s): Sixteen weeks of blinded treatment with pioglitazone (30 mg/d) or placebo. Main Outcome Measure(s): Total and free carnitine and acylcarnitines. Result(s): Contrary to controls, patients with PCOS were characterized with slightly lower levels of fasting total and free carnitine, its precursors, and derivatives. Total and free carnitine correlated inversely to sex hormone-binding globulin (SHBG) in patients with PCOS, whereas no associations were found between acylcarnitines and androgenes. Insulin stimulation-induced changes in the levels of total and free carnitine, carnitine precursors, and acylcarnitines in the PCOS group followed the same trends as in the control group. Pioglitazone treatment significantly increased fasting levels of serum-free carnitine, propionyl carnitine, and total carnitine. The analysis of between group differences revealed significant changes in the isovaleryl carnitine levels and lipid oxidation rates after pioglitazone treatment compared with placebo. Conclusion(s): Acute insulin stimulation was associated with increased serum levels of free carnitine in both patients and healthy controls. Treatment with pioglitazone is able to redistribute free fatty acids from insulin-sensitive tissues, diminish demand for carnitine, and influence the overall carnitine turnover. Clinical Trial Registration Number: NCT00145340. (Fertil Steril (R) 2012; 98: 1620-6. (C) 2012 by American Society for Reproductive Medicine.)