ST elevation myocardial infarction glucose control

For patient information click here

Editors-In-Chief: Anne-Marie Anagnostopoulos, M.D. and C. Michael Gibson, M.S., M.D.

Glucose Control in Acute ST Segment Elevation MI (STEMI)

 * Hyperglycemia has multiple adverse cardiovascular effects, especially in the setting of acute coronary syndromes, and it has been associated with worse clinical outcomes among patients with STEMI. Physiologically, acute hyperglycemia can result in endothelial dysfunction, impaired flow-mediated vasodilation, platelet hyperactivity, and impaired microcirculatory function.. Possible explanations for these adverse effects include activation of pro-inflammatory transcription factors, increased free radicals and increased plasminogen activator inhibitor-1. Among STEMI patients in particular, elevated glucose is associated with reduced TIMI 3 flow pre-intervention, lower rates of reperfusion, as well as impaired myocardial perfusion after successful intervention. Moreover, patients with hyperglycemia are often relatively insulinopenic; insulin has many cardiovascular benefits independent of glucose lowering including coronary vasodilation, improved endothelial and platelet function, decreased thromboxane AII levels, and  anti-inflammatory effects as well.


 * Although hyperglycemia is observed in approximately 50% of  STEMI patients at the time of presention,  only approximately 20-25% of STEMI patients have a prior diagnosis of diabetes.  Elevated glucose and hemoglobin A1c levels are independent predictors of short and long-term cardiovascular outcomes as found in the DIGAMI study.  Admission glucose has been identified as a major correlate of in-hospital CHF and mortality in STEMI. One study found that for every 18mg/dL rise in glucose there was a 4% increase in mortality in non-diabetic patients.


 * In addition to the association of hyperglycemia with adverse outcomes, hypoglycemia has also been associated with poorer clinical outcomes.  When glucose data from a large number of patients enrolled in multiple TIMI trials was analyzed retrospectively, a U-shaped relationship was found between the admission glucose level and adverse outcomes among STEMI patients. In patients with hypoglycemia (glucose <81 mg/dL), the death or MI rate was 10.5% compared to 4.2% in patients with euglycemia (glucose 81-99 mg/dL) and 7.2% in those with hyperglycemia (glucose >199 mg/dL)(3 way  p-value was significant at <0.001. )


 * More recently, as admission hyperglycemia can be “stress induced” in the setting of an MI, fasting glucose levels in both STEMI and non-STEMI was found to be associated with worse in-hospital and 6 month mortality. Investigators used The Global Registry of Acute Coronary Events (GRACE registry) and analyzed 13,000 available fasting glucose levels in patients who presented with a range of acute coronary syndromes.


 * Baseline characteristics of the patients analyzed from the GRACE registry revealed that only 60% of patients with a fasting glucose >126 mg/dL had a prior diagnosis of diabetes. Also, patients with higher fasting glucose levels included women, those with higher Killip class, hypertension, prior stroke or TIA, and peripheral arterial disease. Patients were stratified into  5 different groups according to the fasting glucose level (<100, 100-125, 126-199, 200-299, and >/= 300 mg/dL).  Among STEMI patients, in-hospital death increased as glucose level increased (this was also true for NSTEMI and unstable angina as well).  At 6 months, increasing fasting glucose was associated with higher risk of post-discharge death among STEMI and NSTEMI patients (however, there was no similar association for unstable angina patients).


 * These observations provided the basis for randomized trials evaluating glucose management in the setting of STEMI.


 * Initially, the CREATE-ECLA study used a “metabolic cocktail” (glucose, insulin and potassium or GIK) in STEMI patients to not only treat glucose levels but also to stabilize cell membranes using potassium. However, there was no mortality benefit in patients treated with GIK. Also, the DIGAMI-2 trial attempted to establish that chronic insulin based therapy in STEMI patients would result in improved mortality rates.  however, the study results did not support that hypothesis. Despite these initial negative studies, the question of how best to manage glucose effectively in STEMI patients, and if it will lead to improved survival, remains unanswered.


 * There are currently trials underway that are addressing whether aggressive glucose control with insulin in STEMI patients (particularly anterior STEMI) improves infarct size and cardiovascular outcomes.

==ACC / AHA Guidelines (DO NOT EDIT) ==

{{cquote|

Class IIa
1. It is reasonable to use an insulin-based regimen to achieve and maintain glucose levels less than 180 mg/dL while avoiding hypoglycemia for patients with STEMI with either a complicated or uncomplicated course. (Level of Evidence: B)}}