Anti-Inflammatory and Profibrinolytic Effect of Insulin in Acute ST-Segment–Elevation Myocardial Infarction

Abstract

Background— The clinical benefits of insulin previously observed in acute ST-segment–elevation myocardial infarction (STEMI) may be partially explained by an anti-inflammatory effect. We assessed this potential effect of insulin in STEMI patients treated with fibrinolytics. Methods and Results— Thirty-two patients receiving reteplase were randomly assigned infusions of either insulin at 2.5 U/h, dextrose, and potassium (GIK) or normal saline and potassium (C) for 48 hours. Plasma concentrations of high-sensitivity C-reactive protein (CRP), serum amyloid A (SAA), plasminogen activator inhibitor-1 (PAI-1), creatine kinase (CK), and CK-MB were measured at baseline and sequentially for 48 hours. Total p47 phox protein in mononuclear cells was measured in a subgroup of 13 subjects. Baseline CRP and SAA were significantly increased (2- to 4-fold) at 24 and 48 hours in each group ( P <0.01). However, in the insulin group, there was a significant ( P <0.05) attenuation of the absolute rise in concentration of CRP and SAA from baseline. The absolute increase of CRP and SAA was reduced by 40% (CRP) and 50% (SAA) at 24 hours and at 48 hours compared with the control group. The absolute increase in PAI-1 from baseline and the percentage increase in p47 phox over 48 hours were significantly ( P <0.05) lower in the insulin-treated group. CK-MB peaked earlier and tended to be lower in insulin-treated subjects, especially in patients with inferior MI. Conclusions— Insulin has an anti-inflammatory and profibrinolytic effect in patients with acute MI. These effects may contribute to the clinical benefits of insulin in STEMI.