Effects of insulin on the cardiac autonomic nervous system in insulin-resistant states

The effects of insulin infusion on cardiac autonomic nervous system (ANS) activity were investigated in healthy subjects (n = 15) and in patients with various types of insulin-resistance, such as obese subjects (n = 20) and those with hypertension (n = 15) or type II (non-insulin-dependent) diabetes (n = 22). Healthy subjects and patients underwent euglycaemic hyperinsulinaemic glucose clamp, and cardiac ANS and haemodynamic changes were investigated by continuous recording of heart rate variability by the Holter technique and by venous occlusion plethysmography respectively. At baseline, healthy subjects had the highest values for total spectral power and the low-frequency (LF) component, and the lowest value for the high-frequency (HF) component. In the pooled data (n = 72), the fasting plasma insulin concentration was correlated with baseline total spectral power (r = -0.37; P< 0.001) and the LF/HF ratio (r = -0.35; P< 0.003). Such correlations were still significant (P< 0.01 for both) after adjustment for body fat and mean arterial blood pressure. In a multivariate linear stepwise analysis (n = 72), a model including body fat, waist/hip ratio, fasting plasma glucose concentration and insulin-mediated glucose uptake explained 47% of the variability of the change in the LF/HF ratio, with body fat (t = -3.11; P< 0.01) and insulin-mediated glucose uptake (t = -3.48; P< 0.008) being significantly and independently associated with insulin-mediated changes in the LF/HF ratio. Insulin infusion reduced the total spectral power and increased the LF/HF ratio in healthy subjects, but not in insulin-resistant patients. In conclusion, our study demonstrates that insulin fails to stimulate cardiac ANS activity in insulin-resistant patients, independently of the causes of insulin resistance.