Insulin induced increase in coronary flow reserve is abolished by dexamethasone in young men with uncomplicated type 1 diabetes

Abstract

Objective: To examine the role of the sympathetic nervous system in regulating insulin's action on coronary perfusion in uncomplicated type 1 diabetes by blocking centrally mediated sympathetic activity with dexamethasone.

Methods: Positron emission tomography and oxygen 15 labelled water were used to quantify myocardial blood flow basally and during adenosine infusion with or without simultaneous euglycaemic physiological hyperinsulinaemia in nine non-smoking men with type 1 diabetes and 12 healthy non-diabetic men. Each patient was studied both with and without previous dexamethasone treatment for two days (2 mg/day).

Results: Insulin increased coronary flow reserve in diabetic (from 4.3 (0.7) to 5.1 (0.6), p < 0.05) and non-diabetic (from 4.3 (0.3) to 5.4 (0.4), p < 0.05) patients. In contrast to non-diabetic patients dexamethasone pretreatment abolished the insulin induced increase in coronary flow reserve in diabetic patients (p < 0.05) leading to lower coronary flow reserve in diabetic than in non-diabetic patients (3.9 (0.6) v 7.1 (0.9), p < 0.05).

Conclusions: These results show that insulin's ability to modulate coronary perfusion is sustained in young patients with type 1 diabetes without microvascular complications or autonomic neuropathy. Dexamethasone treatment abolished the insulin induced increase in coronary flow reserve in diabetic patients but not in healthy study participants, suggesting that sympathetic activation plays an important part in regulating insulin's effects on myocardial perfusion in patients with type 1 diabetes.

Figure 1

Design of the study. Myocardial perfusion was measured with oxygen-15 labelled water ([¹⁵O]H₂O) three times: once during basal conditions and twice during adenosine stimulation without and with simultaneous insulin infusion. Insulin was infused at a rate of 1 mU/kg/min.

Figure 2

Coronary flow reserve basally and during insulin infusion without (dx−) and with dexamethasone treatment (dx+) in patients with and without type 1 diabetes. *p < 0.05 v basal, †p < 0.05 v non-diabetic.