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Effect of pioglitazone on cardiac sympathovagal modulation in patients with type 2 diabetes

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Abstract

This study aims to examine the effect of pioglitazone 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 clinostatism 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 sympathovagal 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.

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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

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Acknowledgments

Medical writing support for this manuscript was provided by Primula Multimedia S.R.L., Pisa, Italy. This support was funded by an unconditional grant from Takeda Italia Farmaceutici S.p.A.

Conflict of interest

The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Genoa, Viale Benedetto XV,6, 16132, Genoa, Italy

    F. E. Gianiorio

  2. Department of Endocrinological and Medical Sciences, University of Genoa, Genoa, Italy

    M. Casu, V. Patrone & G. Murialdo

  3. Primula Multimedia S.R.L., Pisa, Italy

    C. G. Egan

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  1. F. E. Gianiorio
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  2. M. Casu
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Correspondence to F. E. Gianiorio.

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Gianiorio, F.E., Casu, M., Patrone, V. et al. Effect of pioglitazone on cardiac sympathovagal modulation in patients with type 2 diabetes. Acta Diabetol 48, 283–290 (2011). https://doi.org/10.1007/s00592-011-0258-0

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