Intensive insulin therapy in diabetic cardiac patients
Patients with diabetes are not only at increased risk of cardiovascular disease (CVD) and myocardial infarction (MI), but are also more likely to have complications, increased mortality and recurrent infections.
A large prospective study of people with type 2 diabetes (n= 48,444), confirmed that increased HbA1c is an independent risk factor for CVD. With every 1% increase in HbA1c levels over a period of 2.4 years, there was an associated 8% increase in MI and a 9% increase in stroke.
Donahoe et al, found that mortality at 30 days was significantly higher among patients with diabetes than without diabetes presenting with unstable angina/non-ST-segment elevated MI (UA/STEMI) (2.1% vs 1.1% p< .001) and STEMI (8.5% vs 5.4% p< .001).
Acute hyperglycaemia can reduce nitric oxide availability, causing a state of increased vasomotor tone and platelet activity. In theory, reduced in-vivo nitric oxide availability increases intracellular calcium content, leading to increased ventricular stiffness and prolonged cardiac repolarisation time.
A prolonged heart rate adjusted QT (QTc) is a risk factor for sudden death and Marfella et al (1999) found that acute hyperglycaemia produces significant increases of QTc and QTc dispersion. Acute elevations in plasma glucose and free fatty acid concentrations, which may occur in acute MI, could cause QTc lengthening and increased QTc dispersion, increasing the risk of arrhythmias and sudden death.
The relationship between admission hyperglycaemia and short term (in-hospital) mortality in patients with and without known diabetes has been well-established. Interestingly, subjects with unknown diabetes and admission glucose levels of 200 mg/dL (11.1 mmol/L) or more after acute MI have mortality rates comparable to those of subjects with established diabetes.
The DIAGMI (Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction) studies evaluated whether aggressive initial insulin therapy, continued for 3 months, would improve morbidity and mortality following an acute MI.
Disappointingly, neither DIAGMI study provided any conclusive evidence that a) an IV insulin-glucose infusion followed by multi-dose subcutaneous insulin, b) an insulin-glucose infusion followed by conventional therapy or c) conventional therapy only, led to improved survival in patients with type 2 diabetes following acute MI.
In a 2006 commentary, Soran et al, cited an increasing body of evidence to suggest that preventing hyperglycaemia and subsequent glucose toxicity is an effective, safe and practicable way of reducing mortality and morbidity in post acute MI and other acutely ill patients.
Until further long-term studies, evaluating the role of IV insulin following acute MI are conducted, the authors concluded that there may be a role for in-hospital insulin-glucose infusion in patients with acute MI and blood glucose concentrations >11 mmol/L.