by Luca Monge, MD

Cardiovascular (CV) disease is the leading cause of death in people with diabetes. Hypoglycemia is a very common side effect of insulin therapy, and to a lesser extent of treatment with some oral hypoglycemic agents. Episodes of severe hypoglycemia are not uncommon during intensive therapy in both type 1 (T1D) and type 2 diabetes (T2D). There is now good evidence that severe hypoglycemia can provoke adverse CV outcomes such as myocardial ischemia or cardiac arrhythmia. However, to date there has been only somewhat limited information quantifying the relationship between hypoglycemia and CV outcomes, which requires large studies.

These authors analyzed data from the very large Explorys database, which contains health information on over 60 million individuals. Of these, 4,882,710 had T2D and 182,220 had episodes of hypoglycemia. Patients with >5 hypoglycemia episodes per year had more overall adverse CV events (OR 1.61), cardiac arrythmias (1.65), and more myocardial infarctions (OR 1.43) compared to those with less than 5 events per year. While these results largely confirm prior studies, they significantly expand previous findings due to the large number of patients included in the analysis. They also reinforce the possibility of a sort of dose-response relationship, wherein individuals experiencing more severe hypoglycemia events have a higher risk of CV events than those who experience fewer events. A causal relation between severe hypoglycemia and CV events thus has practical implications for selecting anti-diabetic agents.

Accordingly, therapies and medication regimens with a low risk for severe hypoglycemia should be preferentially used to reduce the risk of CV events. This would be especially important in patients with established CV disease or in those at high risk, including the elderly. In this regard, the study also found that patients ≥65 years had an incidence of 36% of having a CV event vs. 25% in age-matched controls.

The ongoing challenge for physicians is to lower blood glucose to normal or near normal values to decrease the risk for long-term complications, while minimizing the risk of hypoglycemia and hypoglycemia-associated morbidity and mortality. This study provides additional evidence for a clear relationship between CV events and severe hypoglycemia.