High-Dose Simvastatin Induce Insulin Resistance During Acute Myocardial Infarction by Inhibiting Intracellular Insulin Signaling, Without Attenuating Its Clinical Benefit

Background: Hyperglycemia during the acute phase of myocardial infarction (MI) is a strong marker of mortality, but statin use in this set can potentially induce dysglycemia. We aimed to identify whether statins also induce hyperglycemia during MI and the related mechanisms as well as to evaluate its clinical relevance. Methods: We prospectively studied 550 patients with ST-elevation MI treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day. Of these, 27 non-diabetics were randomized to S10 or S80mg/day and performed euglycemic hyperinsulinemic clamp (EHC) associated with abdominal adipose tissue biopsy after 40 minutes of insulin infusion in the second (D2) and sixth (D6) days after MI. Measurements of plasma glucose, insulin, C-peptide on admission (D1) and fifth (D5) day were performed in all patients. Results: Between D2 and D6, insulin sensitivity index (ISi) measured by EHC increased (20±60%) in the S10 group and reduced (-6±28%) in S80 (p=0.025). Analysis of the biopsies by Western-blo...