Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction

Circulation. 2004 Feb 24;109(7):849-54. doi: 10.1161/01.CIR.0000116762.77804.FC. Epub 2004 Feb 2.

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 p47phox 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 p47phox 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Blood Glucose / analysis
  • C-Reactive Protein / analysis
  • Comorbidity
  • Creatine Kinase / blood
  • Creatine Kinase, MB Form
  • Drug Therapy, Combination
  • Electrocardiography
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / pharmacology
  • Fibrinolytic Agents / therapeutic use*
  • Humans
  • Inflammation / blood
  • Insulin / administration & dosage
  • Insulin / pharmacology
  • Insulin / therapeutic use*
  • Isoenzymes / blood
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / physiopathology
  • NADPH Oxidases
  • Phosphoproteins / blood
  • Plasminogen Activator Inhibitor 1 / blood
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Serum Amyloid A Protein / analysis
  • Thrombolytic Therapy
  • Tissue Plasminogen Activator / administration & dosage
  • Tissue Plasminogen Activator / therapeutic use
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Blood Glucose
  • Fibrinolytic Agents
  • Insulin
  • Isoenzymes
  • Phosphoproteins
  • Plasminogen Activator Inhibitor 1
  • Recombinant Proteins
  • Serum Amyloid A Protein
  • C-Reactive Protein
  • reteplase
  • NADPH Oxidases
  • neutrophil cytosolic factor 1
  • Creatine Kinase
  • Creatine Kinase, MB Form
  • Tissue Plasminogen Activator