Risk of Cardiac Arrhythmias During Hypoglycemia in Patients With Type 2 Diabetes and Cardiovascular Risk

Abstract

Recent trials of intensive glycemic control suggest a possible link between hypoglycemia and excess cardiovascular mortality in patients with type 2 diabetes. Hypoglycemia might cause arrhythmias through effects on cardiac repolarization and changes in cardiac autonomic activity. Our aim was to study the risk of arrhythmias during spontaneous hypoglycemia in type 2 diabetic patients with cardiovascular risk. Twenty-five insulin-treated patients with type 2 diabetes and a history of cardiovascular disease or two or more risk factors underwent simultaneous continuous interstitial glucose and ambulatory electrocardiogram monitoring. Frequency of arrhythmias, heart rate variability, and markers of cardiac repolarization were compared between hypoglycemia and euglycemia and between hyperglycemia and euglycemia matched for time of day. There were 134 h of recording at hypoglycemia, 65 h at hyperglycemia, and 1,258 h at euglycemia. Bradycardia and atrial and ventricular ectopic counts were significantly higher during nocturnal hypoglycemia compared with euglycemia. Arrhythmias were more frequent during nocturnal versus daytime hypoglycemia. Excessive compensatory vagal activation after the counterregulatory phase may account for bradycardia and associated arrhythmias. QT intervals, corrected for heart rate, >500 ms and abnormal T-wave morphology were observed during hypoglycemia in some participants. Hypoglycemia, frequently asymptomatic and prolonged, may increase the risk of arrhythmias in patients with type 2 diabetes and high cardiovascular risk. This is a plausible mechanism that could contribute to increased cardiovascular mortality during intensive glycemic therapy.

Management of Atherosclerotic Cardiovascular Disease Risk Factors in the Older Adult Patient With Diabetes

“…In studies using continuous glucose and cardiac monitoring devices, hypoglycemia was associated with an increase in arrhythmias and prolonged QT intervals (75). Enhanced sympathetic nervous system activation, catecholamine excess, and abnormal cardiac repolarization observed with hypoglycemia can potentially contribute to ASCVD risk and events (85,86).…”

Design of FLAT-SUGAR: Randomized Trial of Prandial Insulin Versus Prandial GLP-1 Receptor Agonist Together With Basal Insulin and Metformin for High-Risk Type 2 Diabetes

“…The reasons for failure of the HbA 1c -based glycemic control strategies used in these more recent studies are not clear, but one possibility is that HbA 1c levels do not assess variability in plasma glucose levels; that is, HbA 1c does not directly reflect the frequency or severity of either hypoglycemic events or hyperglycemic increments after meals, both of which may cause physiologic changes that contribute to long-term risks. Possible mechanisms for such effects include systemic inflammation (8,9), oxidative stress (10), endothelial dysfunction (11,12), intimal-medial thickening (13), and cardiac ischemia or arrhythmias (14)(15)(16). Considerable literature linking various CVD risk markers with glycemic variability has been published (17,18).…”

Predicting risk of severe hypoglycaemia in type 2 diabetes

“…The obvious question of whether the relationship between severe hypoglycaemia and mortality is causal or mere association remains undetermined [5]. Although experimental studies in humans and rodents have identified potential mechanistic changes that could explain an association, for example, by inducing cardiac dysrhythmias [6,7], infrequent fatal events are difficult to study at a population level. However, whether it increases the risk of dying or not, hypoglycaemia is still clinically important, being feared by patients as much as chronic complications, increasing the risk of accidents, carrying social and economic costs (e.g.…”