Insulin therapy in type 2 diabetes post MI

Evidence suggests that intense metabolic control using insulin does not lead to an improvement in mortality and morbidity in Type 2 diabetic patients after acute myocardial infarction. The study results do however suggest that glucose control is an important part of management of this cohort of patients

• patients with type 2 diabetes have an unfavourable prognosis after an acute myocardial infarction
• in the first DIGAMI study, an insulin-based glucose management for patients with type 2 diabetes led to improved survival
• in DIGAMI 2, three treatment strategies were compared:
  • group 1, acute insulin-glucose infusion followed by insulin-based long-term glucose control;
  • group 2, insulin-glucose infusion followed by standard glucose control;
  • group 3, routine metabolic management according to local practice
  • the study recruited 1253 patients (mean age 68 years; 67% males) with type 2 diabetes and suspected acute myocardial infarction randomly assigned to groups 1 (n=474), 2 (n=473), and 3 (n=306)
    • primary endpoint was all-cause mortality between groups 1 and 2, and a difference was hypothesized as the primary objective
    • secondary objective was to compare total mortality between groups 2 and 3, whereas morbidity differences served as tertiary objectives
      • median study duration was 2.1 years.
      • by the end of follow-up, HbA1c did not differ significantly among groups 1-3 ( approximately 6.8%)
      • corresponding values for fasting blood glucose were 8.0, 8.3, and 8.6 mmol/L
      • note that the target fasting blood glucose for patients in group 1 of 5-7 mmol/L was never realised in this study
      • study mortality (groups 1-3 combined) was 18.4%
        • mortality between groups 1 (23.4%) and 2 (22.6%; primary endpoint) did not differ significantly, nor did mortality between groups 2 (22.6%) and 3 (19.3%)
        • there were no significant differences in morbidity expressed as non-fatal reinfarctions and strokes among the three groups

The study results from DIGAMI 2 does not support the using of an acutely introduced long-term insulin treatment to improve survival in type 2 diabetic patients following myocardial infarction (when compared with a conventional management at similar levels of glucose control). Also this study also does not provide evidence that insulin-based treatment lowers the number of non-fatal myocardial reinfarctions and strokes. However, an epidemiological analysis confirms that the glucose level is a strong, independent predictor of long-term mortality in this patient category, underlining that glucose control seems to be an important part of their management.

NICE state with respect to hyperglycaemia in acute coronary syndromes (3):

• managing hyperglycaemia in inpatients within 48 hours of acute coronary syndrome
  • manage hyperglycaemia in people admitted to hospital for an acute coronary syndrome by keeping blood glucose levels below 11.0 mmol/litre while avoiding hypoglycaemia. In the first instance, consider a dose-adjusted insulin infusion with regular monitoring of blood glucose levels
  • do not routinely offer intensive insulin therapy (an intravenous infusion of insulin and glucose with or without potassium) to manage hyperglycaemia (blood glucose above 11.0 mmol/litre) in people admitted to hospital for an acute coronary syndrome unless clinically indicated

Notes:

• at randomization participants had already relatively good glycaemic control; HbA1c was 7.2, 7.3, and 7.3% in groups 1, 2, and 3, respectively, whereas blood glucose was 12.8, 12.5, and 12.9 mmol/L, respectively
• intensive intraoperative insulin therapy during cardiac surgery
  • a study revealed that intensive insulin therapy during cardiac surgery does not reduce perioperative death or morbidity. There was an increased incidence of death and stroke in the intensive treatment group (3)

Reference:

1. Malberg K et al.Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J. 2005 Apr;26(7):650-61
2. NICE (April 2001). Summary of Guidance issued to the NSH in England and Wales, MI prophylaxis - drug treatment, cardiac rehabilitation and dietary manipulation, 2, 9-14
3. NICE (November 2020). Acute coronary syndromes.
4. Ghandi GY et al. Intensive intraoperative insulin therapy versus conventional glucose management during cardiac surgery: a randomized trial. Ann Intern Med. 2007 Feb 20;146(4):233-43.