Associations of hypoglycemia, glycemic variability and risk of cardiac arrhythmias in insulin-treated patients with type 2 diabetes: a prospective, observational study

Background: Insulin-treated patients with type 2 diabetes (T2D) are at risk of hypoglycemia, which is associated with an increased risk of cardiovascular disease and mortality. Using a long-term monitoring approach, we investigated the association between episodes of hypoglycemia, glycemic variability and cardiac arrhythmias in a real-life setting. Methods: Insulin-treated patients with T2D (N = 21, [mean ± SD] age 66.8 ± 9.6 years, BMI 30.1 ± 4.5 kg/m2, HbA1c 6.8 ± 0.4% [51.0 ± 4.8 mmol/mol]) were included for a one-year observational study. Patients were monitored with continuous glucose monitoring ([mean ± SD] 118 ± 6 days) and an implantable cardiac monitor (ICM) during the study period. Results: Time spend in hypoglycemia was higher during nighttime than during daytime ([median and interquartile range] 0.7% [0.7–2.7] vs. 0.4% [0.2–0.8]). The ICMs detected 724 episodes of potentially clinically significant arrhythmias in 12 (57%) participants, with atrial fibrillation and pauses accounting for 99% of the episodes. No association between hypoglycemia and cardiac arrhythmia was found during daytime. During nighttime, subject-specific hourly incidence of cardiac arrhythmias tended to increase with the occurrence of hypoglycemia (incident rate ratio [IRR] 1.70 [95% CI 0.36–8.01]) but only slightly with increasing time in hypoglycemia (IRR 1.04 [95% CI 0.89–1.22] per 5 min). Subject-specific incidence of cardiac arrhythmias during nighttime increased with increasing glycemic variability as estimated by coefficient of variation whereas it decreased during daytime (IRR 1.33 [95% CI 1.05–1.67] and IRR 0.77 [95% CI 0.59–0.99] per 5% absolute increase, respectively). Conclusions: Cardiac arrhythmias were common in insulin-treated patients with T2D and were associated with glycemic variability, whereas arrhythmias were not strongly associated with hypoglycemia. Trial registration: NCT03150030, ClinicalTrials.gov, registered May 11, 2017. https://clinicaltrials.gov/ct2/show/NCT03150030.