The Effect of Hyperinsulinaemic Euglycaemia on Myocardial Blood Flow Reserve in Healthy Volunteers Over Time

Abstract

Background and Aims: The vasodilator effect of insulin is incompletely understood. Previous insulin use in acute coronary syndrome trials have shown disappointing results. Our group has shown that hyperinsulinaemic euglycaemia increases myocardial blood flow reserve (MBFR) by 20% in healthy individuals. The time taken for hyperinsulinaemia to exert an effect on the coronary microcirculation is unknown. It is also not known whether this effect can diminish with time. This study investigated the relationship between hyperinsulinaemic clamp time on MBFR. Method & Results: Five healthy male volunteers (mean age 37 yrs (range 21-54)) underwent hyperinsulinaemic euglycaemic clamps. Low-power real-time myocardial contrast echocardiography was performed with flash impulse imaging using low-dose adenosine stress to measure MBFR at baseline. This was repeated at 30, 60, and 120 minutes after commencing insulin infusion at a fixed concentration of 1.5mU/kg/min. Mean(SD) baseline MBFR was 2.5(0.3). MBFR values at 30, 60 and 120 minutes were 3.1(0.8), 3.5(0.6), and 4.1(0.8), respectively. This represents an increase in MBFR of 24%, 40% and 64% with respect to baseline values. Mean fasting serum insulin was 2.3(1.8), 43.2(30.8), 50.6(20.9), and 45.8(21.5) mU/L, respectively. There was no significant difference between baseline and 30-minute MBFR (p=0.06). However there were significant increases in MBFR between baseline versus 60mins (p=0.009), and 60 versus 120mins (p=0.006). Conclusion: Hyperinsulinaemic euglycaemia increases MBFR significantly at 60 minutes of commencing hyperinsulinaemic clamps. This effect is maintained at 120 minutes.