ORIGINAL ARTICLE Effect of pioglitazone on systemic inflammation is independent of metabolic control and cardiac autonomic function in patients with type 2 diabetes Roberto Nerla Æ Dario Pitocco Æ Francesco Zaccardi Æ Giancarla Scalone Æ Ilaria Coviello Æ Roberto Mollo Æ Giovanni Ghirlanda Æ Gaetano A. Lanza Æ Filippo Crea Received: 29 April 2009 / Accepted: 14 September 2009 / Published online: 29 September 2009 Ó Springer-Verlag 2009 Abstract The aim of this article is to investigate the relation of the anti-inflammatory effect of pioglitazone with cardiac autonomic function and metabolic control in dia- betic patients. In this prospective open label trial, 36 type 2 diabetic patients (age 60 ± 10, 20 M) without overt car- diovascular disease were randomized to add pioglitazone (30 mg) to their therapy or to continue standard therapy. C-reactive protein (CRP) serum levels, metabolic parame- ters and cardiac autonomic function (assessed by heart rate variability [HRV] on 24-h ECG Holter monitoring) were measured at baseline and after 3 months. Clinical and laboratory variables were similar in the two groups. No significant changes were observed after 3 months for met- abolic and anthropometric parameters, except for a mild increase in HDL levels in the pioglitazone group only (P = 0.04 vs. controls). CRP levels decreased significantly at follow-up in the pioglitazone group (3.2 ± 1.97 vs. 2.37 ± 1.56 mg/l) but not in the control group (3.0 ± 1.92 vs. 3.93 ± 2.14 mg/l; P = 0.003). No differences were found in basal and follow-up HRV variables between the two groups. In type 2 diabetic patients pioglitazone exerts favourable effects on inflammation even after short-term therapy. This effect precedes those on metabolic and anthropometric parameters and is not associated with changes in cardiac autonomic function. Keywords Pioglitazone Á Cardiac autonomic function Á Inflammatory markers Á Metabolic control Abbreviations CRP C-reactive protein FPG Fasting plasma glucose HRV Heart rate variability LF Low frequency amplitude HF High frequency amplitude PPAR Peroxisome proliferator-activated receptors SDNN Standard deviation of NN intervals SDNNi Mean of the standard deviations of NN intervals of all 5 min segments in the recording VLF Very low frequency amplitude Introduction Pioglitazone is an antidiabetic drug known to decrease peripheral, hepatic, and vascular insulin resistance by stimulation of peroxisome proliferator-activated receptors gamma (PPARgamma), which are known to modulate several functions in several cell types (neurons, endothelial cells, macrophages, adipocytes) [1]. In type 2 diabetic patients pioglitazone has been shown to have favourable effects on vascular function, including improvement of endothelial function and reduction of blood pressure; furthermore, in clinical trials, the drug has been shown to reduce macrovascular events [2]. R. Nerla and D. Pitocco contributed equally to this article. R. Nerla Á G. Scalone Á I. Coviello Á R. Mollo Á G. A. Lanza (&) Á F. Crea Istituto di Cardiologia, Universita ` Cattolica del Sacro Cuore, Largo A. Gemelli, 8, 00168 Rome, Italy e-mail: g.a.lanza@rm.unicatt.it D. Pitocco Á F. Zaccardi Á G. Ghirlanda Servizio di Diabetologia, Universita ` Cattolica del Sacro Cuore, Rome, Italy 123 Acta Diabetol (2010) 47 (Suppl 1):S117–S122 DOI 10.1007/s00592-009-0150-3