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Metformin May Improve Cardiac Autonomic System Balance in Overweight Patients with Type 2 Diabetes

Metformin may improve cardiac autonomic system balance through its effects on plasma free fatty acids and insulin resistance, according to a new Italian study.

Hyperinsulinaemia is known to increase cardiovascular mortality in patients with type 2 diabetes due to sympathetic overactivity. Recent reports have suggested that elevated plasma free fatty acid (FFA) concentrations may also contribute to a stimulation of the cardiac autonomic nervous system in these patients.

Treatment with metformin improves insulin action and lowers plasma FFA concentrations. Therefore, it is possible that metformin may also affect the cardiac autonomic nervous system indirectly.

To address this possibility, Giuseppe Paolisso, MD, of Second University of Naples, Italy, and colleagues investigated the effects of metformin versus placebo treatment on cardiac autonomic nervous activity in 120 overweight patients with type 2 diabetes (mean age, 57 ± 11 years; 64 males).

Sixty participants were randomly assigned to placebo and 60 to metformin 850 mg twice daily for a period of 4 months. All patients consumed a weight-stable diet during the study period. Venous blood samples were drawn at the start and end of the trial for evaluation of plasma metabolites. Insulin resistance was assessed by the Homeostasis Model Assessment (HOMA), and cardiac autonomic nervous activity by heart rate variability.

Metformin treatment was associated with decreases in fasting glucose (P < .05), insulin (P < .05), triglycerides (P < .05), FFA concentrations (P < .03), and HOMA index (P < .03). The researchers also detected a significant improvement in cardiac sympathovagal balance in the metformin group, including increases in RR interval, total power and high frequency (P < .05 for all), and decreases in low frequency (LF; P < .05) and LF/HF ratio (P < .02). Metformin did not improve mean arterial blood pressure.

In addition, the researchers performed a multivariate analysis with LF/HF as the dependent variable, and gender, changes in HOMA index, plasma FFA, triglyceride, and HbA1c as independent variables. Changes in LF/HF ratio were found to be independently and significantly associated with changes in both plasma FFA level (P < .01) and HOMA index (P < .03).

"Metformin-related changes in plasma FFA and in insulin resistance may be useful to improve autonomic nervous system balance at the cardiac level but not arterial BP in overweight type 2 diabetic patients," the researchers conclude.

Am J Hypertens 2004 Mar;17:3:223-7. "Blood pressure and cardiac autonomic nervous system in obese type 2 diabetic patients: effect of metformin administration"

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