Effect of Statin Treatment on Insulin Sensitivity During Myocardial Infarction

Study Overview
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Brief Summary
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Stress hyperglycemia during myocardial infarction (MI) is related to mortality at short and long term. Recent studies, however, revealed that chronic statin treatment may decrease both insulin sensitivity and secretion immediately after statin therapy initiation. This study aim was to investigate the dose-dependent effect of statins on insulin sensitivity in patients in the acute phase of MI.

Detailed Description
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Stress hyperglycemia during myocardial infarction (MI) is a predictor of worse prognosis at short and long term. From the mechanistic standpoint, hyperglycemia can attenuate thrombolysis, increase platelet aggregation, induce coronary vasoconstriction, reduce oxygen transport and prolong endothelial inflammation after MI. Consistently, observational data indicates that glucose normalization improves survival in hyperglycemic patients hospitalized with MI. High dose potent statins have been included in the early treatment of acute coronary syndromes (ACS) based upon a broad range of potentially beneficial mechanisms. Recent studies, however, revealed that chronic statin treatment may increase the incidence of type 2 diabetes mellitus in a dose-dependent manner. Moreover, according to studies in cellular and animal models, such decrease in insulin sensitivity may be observed immediately after statin therapy initiation. By inference, one may speculate that statin treatment initiated at the acute phase of MI may potentially favor the appearance or aggravation of stress hyperglycemia. To date, however, this hypothesis has not been investigated. Hence, this study aim was to investigate the dose-dependent effect of statins on insulin sensitivity in patients in the acute phase of MI.

Official Title
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Phase 4 Study of the Effect of Statin Treatment on Insulin Sensitivity During Myocardial Infarction

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Simvastatin 80mg
* Drug: Simvastatin 10mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Less than 24 hours after the onset of MI symptoms ST-segment elevation of a least 1 mm (frontal plane) or 2 mm (horizontal plane) in two contiguous leads Myocardial necrosis, as evidenced by increased Creatine Kinase-MB (CK-MB) and troponin levels Exclusion Criteria: Diabetes or prior use of statins in the last 6 months

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simvastatin 80mg<br>Simvastatin 80mg once a day | Drug: Simvastatin 80mg<br>* Simvastatin 80mg once a day<br>* Other names: Zocor;|
| Active Comparator: Simvastatin 10mg<br>Simvastatin 10mg once a day | Drug: Simvastatin 10mg<br>* Simvastatin 10mg once a day<br>* Other names: Zocor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity | Insulin sensitivity as determined by hyperinsulinemic normoglycemic clamp | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Activation of insulin receptor substrate (IRS-1) and Akt protein | Verify the degree of phosphorylation of insulin receptor substrate (IRS-1) and Akt protein estimated by Western Blotting of the abdominal adipose tissue obtained by biopsy | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Statin, Myocardial infarction, Insulin sensitivity