Cardiac Effects of Sulfonylurea-Related Hypoglycemia

Abstract

OBJECTIVE To determine the effect of sulfonylurea-related hypoglycemia on cardiac repolarization and ectopy in the setting of well-controlled type 2 diabetes.

RESEARCH DESIGN AND METHODS Thirty subjects with sulfonylurea-treated type 2 diabetes underwent 48 h of concurrent continuous glucose monitoring and ambulatory electrocardiography. Ventricular repolarization (QTc) and QT dynamicity were analyzed during periods of hypoglycemia (<3.5 mmol/L for >20 min) and compared with periods of euglycemia and hyperglycemia combined. Cardiac ectopy rates during hypoglycemia were compared with ectopy rates when blood glucose was 4–10 mmol/L.

RESULTS Mean HbA1c was 6.9% (52 mmol/mol). Hypoglycemia was detected in 9 of 30 subjects (30%); episodes were typically nocturnal (67%) and asymptomatic (73%). Hypoglycemia-associated QTc prolongation was seen in five of nine subjects with a large variation in individual response. Higher QT dynamicity, a poor prognostic factor in cardiac disease, was seen in subjects who experienced hypoglycemia compared with subjects who did not (0.193 vs. 0.159 for the nocturnal period; P = 0.01). This finding persisted after the hypoglycemic event. The rates of ventricular and supraventricular ectopy demonstrated a nonsignificant trend toward an increase during hypoglycemia (median rate ratio 1.58 and 1.33, respectively). Similar, nonsignificant results were observed in a separate insulin-treated cohort.

CONCLUSIONS Hypoglycemia, often unrecognized, is a frequent finding in well-controlled sulfonylurea-treated type 2 diabetes. It is associated with the novel finding of increased QT dynamicity and QTc prolongation in some individuals. Our findings suggest sulfonylurea-related hypoglycemia can have detrimental cardiovascular sequelae. Similar effects are also seen in the setting of insulin therapy.

http://care.diabetesjournals.org/content/early/2017/02/19/dc16-1972

Paywalled dammit! I wanted to see if they'd looked at insulin levels.

Some Sulfonylurea drugs affect also ischemic preconditioning that raises the risk of heart attack damage.

New Discoveries: A Possible Mechanism

Recent experimental studies in models of myocardial infarction examining the phenomenon of ischemic preconditioning suggest a possible mechanism whereby sulfonylurea drugs might lead to increased mortality. Preconditioning refers to the observation that a brief period of ischemia may render less severe a subsequent, more prolonged episode.19 For example, a preconditioning episode of 5 minutes of ischemia that causes no cell death followed by reperfusion reduces infarction during a subsequent 30-minute “test” ischemia/reperfusion. Preconditioning has been observed to reduce several types of injury: (1) myocardial infarct size in ischemic and reperfused muscle, (2) myocardial stunning, and (3) arrhythmias.20 21 22 Preconditioning occurs in every animal species that has been tested. The protection from ischemic cell death is the most powerful of any adjunct to reperfusion known to date and is sustained after prolonged reperfusion.21 For example, in the rabbit model, one preconditioning episode can decrease infarct size during a subsequent test infarction from 40% to 8% of the area at risk.20 Changes in hemodynamics or collateral blood flow do not account for the reduction in infarct size. A key mechanism of preconditioning is thought to involve the release of adenosine formed from net ATP utilization during the preconditioning episode of ischemia.

http://circ.ahajournals.org/content/94/9/2297

Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study

https://academic.oup.com/eurheartj/article/32/15/1900/565965/Mortality-and-cardiovascular-risk-associated-with

Thanks, very interesting that the different drugs in the same class have differing effects, well the magnitude anyway.