Effect of Hypoglycemia on QT Interval in Individuals With and Without Type 2 Diabetes: A Randomized Crossover Trial

Our goal was to determine in healthy individuals and individuals with type 2 diabetes the impact of repeated episodes of hypoglycemia on the corrected QT (QTc) interval and the time course for QTc recovery. Further, since hypoglycemia increases aldosterone and patients with primary aldosteronism have prolonged QTc, we also determined whether mineralocorticoid receptor blockade prevents hypoglycemia-induced QTc alterations.

Twenty-seven healthy participants completed a double-blinded crossover trial contrasting 3 experimental conditions: (1) euglycemia, (2) hypoglycemia, and (3) hypoglycemia with mineralocorticoid receptor blockade pretreatment. Sixteen participants with type 2 diabetes completed 1 condition, hypoglycemia. Hyperinsulinemic clamps were performed to induce the hypoglycemic and euglycemic conditions. Electrocardiograms were performed before, during, and after the clamps.

Healthy participants had a significant (P < .0001) prolongation of QTc during both the morning and afternoon hypoglycemic clamps as compared with euglycemic clamps (morning hypoglycemia vs euglycemia: 439.06 ± 41.18 ms vs 406.96 ± 26.16 ms; afternoon hypoglycemia vs euglycemia: 441.50 ± 34.36 ms vs 407.78 ± 19.18 ms). Mineralocorticoid receptor (MR) blockade did not alter the response to hypoglycemia. Participants with diabetes achieved a significant prolongation of QTc during the afternoon hypoglycemia only (afternoon hypoglycemia vs morning baseline: 461.96 ± 49.14 vs 428.90 ± 28.54, P < .05). In both participant populations, QTc intervals were similar to baseline 90 minutes after return to euglycemia and the following day.

Hypoglycemia prolonged QTc in healthy participants, and this was not altered by MR blockade. In individuals with type 2 diabetes, 2 hypoglycemic episodes were required to achieve prolongation. Reassuringly, in both study populations, hypoglycemia-induced QTc prolongation resolved quickly with no apparent residual effects the next day.