ORIGINAL ARTICLE Effect of pioglitazone on cardiac sympathovagal modulation in patients with type 2 diabetes F. E. Gianiorio • M. Casu • V. Patrone • C. G. Egan • G. Murialdo Received: 9 November 2010 / Accepted: 14 January 2011 Ó Springer-Verlag 2011 Abstract This study aims to examine the effect of piog- litazone on potential progression of autonomic damage in addition to changes in control of cardiovascular function in patients with type 2 diabetes (T2DM). Thirty patients with T2DM and 32 healthy subjects participated in the study. Sympathovagal activity, assessed by power spectral analysis (PSA) of R–R intervals variability, and blood pressure (BP) were studied during clinostatism and orthostatism in controls and patients. We have assessed blood pressure control by 24-hour monitoring of ambulatory blood pressure. Patients were treated with pioglitazone (30 mg/day) for 6 months, and then re-evaluated by PSA for heart rate variability (HRV). Reduced levels of HbA1c (P \ 0.0001) and urinary albumin (P = 0.008) were observed in pioglitazone-treated patients compared to untreated baseline levels. Arterial BP remained unchanged following pioglitazone treatment. T2DM patients had reduced HRV (low-frequency power; LF; P \ 0.0001 and LF/HF; LF/HF; P \ 0.0001) at baseline (clinostatism) compared to controls. Baseline clinostatic differences between groups persisted after pioglitazone treatment and no effect of treatment on basal HRV variables was observed. In controls, HF decreased and LF and LF/HF ratio increased in the orthostatic position. A similar effect for HF was observed in patients, but LF and LF/HF did not increase. The normal difference between HF-power in cli- nostatism versus orthostatism observed for controls (P \ 0.0001) was restored in patients following pioglitazone treatment (P = 0.028). A significant decrease from lying to standing position in orthostatic LF-power (P \ 0.0001) and LF/HF (P \ 0.0001) was also observed between patients and controls. Although no differences in autonomic control of HRV were observed between controls and patients with T2DM, significant differences were observed in sympath- ovagal balance following either clinostatic or orthostatic challenge. These findings provide initial evidence of a potential additional benefit afforded by pioglitazone for the improvement of cardiac sympathovagal balance in T2DM. Keywords Type 2 diabetes mellitus Á Pioglitazone Á Power spectral analysis Á Sympathovagal Á Heart rate variability Abbreviations T2DM Type 2 diabetes mellitus HRV Heart rate variability PSA Power spectral analysis ECG Electrocardiogram HR Heart rate LF Low frequency HF High frequency Introduction Individuals diagnosed with metabolic syndrome, including diabetes, dyslipidemia, and hypertension, are at increased F. E. Gianiorio (&) Department of Internal Medicine, University of Genoa, Viale Benedetto XV,6, 16132 Genoa, Italy e-mail: fabioenzo.gianiorio@fastwebnet.it M. Casu Á V. Patrone Á G. Murialdo Department of Endocrinological and Medical Sciences, University of Genoa, Genoa, Italy C. G. Egan Primula Multimedia S.R.L., Pisa, Italy 123 Acta Diabetol DOI 10.1007/s00592-011-0258-0