Relationship between autonomic dysfunction, insulin resistance and hypertension, in diabetes

Sympathovagal imbalance and insulin resistance are the common underlying disorders linking hypertension and diabetes. The rote of hyperinsulinemia, however, on sympathovagal balance and blood pressure has never been clearly dissected from that of hyperglycemia. Nevertheless, the study of animal models of hypertension showed that hypertension does not invariably result in the onset of insulin resistance. This suggests that insulin resistance precedes the onset of hypertension and (possibly) contributes to its pathogenesis, mainly through sympathetic activation. To examine this hypothesis, recent studies investigated the relationship between insulin sensitivity and sympathetic activity in subjects with insulin resistance but free of overt hyperglycemia and obesity, i.e., insulin-resistant offspring of type 2 diabetic patients, demonstrating a prevalence of sympathetic over vagal activity. Therefore insulin resistance and sympathovagal imbalance come before hypertension, but a clear causative role cannot be demonstrated since other mechanisms, including an inappropriate lifestyle, must be taken into account to determine clinical hypertension. Finally, several experiments in human healthy volunteers suggest that the modulation of autonomic regulation at the forearm level can regulate insulin sensitivity, tempting us to speculate that it is the primary autonomic imbalance, through vasoconstriction, that results in both insulin resistance and hypertension. In conclusion, the close relationship between autonomic imbalance, insulin resistance and hypertension is unquestionable; although logical hypothesis can be constructed, which of the three is the earliest event is still not understood, and further research is required. (c) 2005 Elsevier B.V. All rights reserved.