Hypoglycemia may be associated with myocardial damage

Among patients with coronary artery disease, severity and frequency of hypoglycemia were associated with increased levels of high-sensitivity cardiac troponin T, although the association was attenuated in adjusted analyses.


Hypoglycemia was associated with high-sensitivity cardiac troponin T levels in a recent study of patients with type 2 diabetes and stable coronary artery disease.

For one year, researchers prospectively followed and documented hypoglycemic episodes among patients with type 2 diabetes and stable coronary artery disease in the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. They measured high-sensitivity cardiac troponin T at baseline and at one year. Results of the study, which was funded in part by industry, were published online on Oct. 1 by the Journal of the American College of Cardiology.

Of 1,984 participants, follow-up hypoglycemia was absent in 1,026 (52%), mild in 875 (44%), and severe in 83 (4%). High-sensitivity cardiac troponin T levels at one year were associated with severity of hypoglycemia, with a median of 11.4 ng/L (interquartile range [IQR], 8.1 to 17.3 ng/L) for no hypoglycemia, 12.5 ng/L (IQR, 8.3 to 19.3 ng/L) for mild hypoglycemia, and 13.7 ng/L (IQR, 9.9 to 24.9 ng/L) for severe hypoglycemia (P=0.0001).

Hypoglycemia occurred less than weekly in 561 (28%) patients and at least weekly in 397 (20%) patients. Median levels of high-sensitivity cardiac troponin T at one year were associated with frequency of hypoglycemia: 12.5 ng/L (IQR, 8.3 to 18.1 ng/L) for less than weekly and 13.0 ng/L (IQR, 8.8 to 21.1 ng/L) for at least weekly (P=0.0013).

In unadjusted analysis, severe hypoglycemia was associated with 34% higher high-sensitivity troponin T levels at one year than mild hypoglycemia (P<0.0001). This decreased to 17% (P=0.0003) after adjustment for baseline factors unrelated to diabetes and to 6% (P=0.45) after further adjustment for duration and severity of diabetes. Compared to less than weekly hypoglycemia, at least weekly hypoglycemia was associated with 14% higher high-sensitivity troponin T levels (P=0.0003) in unadjusted analysis, 12% higher levels (P=0.00002) after adjustment for baseline factors unrelated to diabetes, and 4% higher levels (P=0.16) after adjustment for diabetes-related factors.

The study authors noted limitations, such as the fact that they measured high-sensitivity cardiac troponin T levels only twice (at baseline and one year), despite assessing hypoglycemia multiple times during follow-up. Thus, they could not assess the trajectory of troponin over follow-up or its relationship to specific episodes of hypoglycemia. They added that they did not collect data on self-monitored glucose levels or hypoglycemia symptoms other than confusion, coma, or convulsions.

The results suggest that “hypoglycemia may be a marker of ongoing subclinical myocardial damage in patients with diabetes, but the mechanism(s) underlying this association is uncertain, and may be due to a constellation of factors related to the severity of diabetes,” the authors concluded.

To minimize the risk of cardiovascular events in patients with diabetes, clinicians should identify patients at risk of severe hypoglycemia and avoid prescribing drugs that are associated with increased risk of hypoglycemia, said an accompanying editorial comment. Recent guidelines, such as ACP's 2018 recommendations including HbA1c goals in a more liberal range of 7% to 8%, emphasize the importance of avoiding hypoglycemia, the editorialist noted. The editorial also pointed out that the 2018 Standards of Medical Care in Diabetes from the American Diabetes Association emphasize that the selection of antidiabetic drugs should be based on a number of factors, including the risk of hypoglycemia.

“It is important that the clinician become familiar with these newer guidelines and consider switching from the use of drugs such as [sulfonylureas] to safer drugs like [sodium-glucose cotransporter-2] inhibitors and [glucagon-like peptide 1] agonists,” the editorialist wrote.