Effect of Hypoglycemia on Heart Rate Variability in People with Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Background:People with impaired awareness of hypoglycemia (IAH) are at elevated risk of severe, potentially hazardous, hypoglycemia and would benefit from a device alerting to hypoglycemia. Heart rate variability (HRV) changes with hypoglycemia due to sympathetic activity. Since IAH is associated with suppressed sympathetic activity, we investigated whether hypoglycemia elicits a measurable change in HRV in patients with T1D and IAH. Method:Eligible participants underwent a modified hyperinsulinemic euglycemic hypoglycemic clamp (glucose nadir, 43.1 +/- 0.90 mg/dl), while HRV was measured by a VitalConnect HealthPatch. Measurements of HRV included Root Mean Square of the Successive Differences (RMSSD) and low to high frequency (LF:HF) ratio. Wilcoxon rank-sum test was used for testing within-subject HRV changes. Results:We included 12 participants (8 female, mean age 57 +/- 12 years, mean HbA1c 57 +/- 5 mmol/mol (7.4 +/- 0.4%)). Symptoms increased from 4.0 (1.5-7.0) at euglycemia to 7.5 (5.0-11.0) during hypoglycemia (P = .003). In response to hypoglycemia, the LF:HF ratio and RMSSD increased when normalized for data obtained during euglycemia (both P < .01). The LF:HF ratio increased in 6 participants (50%) and declined in one other participant (8%). The RMSSD decreased in 3 (25%) and increased in 4 (33%) participants. In 2 patients, no change in HRV could be detected in response to hypoglycemia. Conclusions:This study reveals that hypoglycemia-induced changes in HRV are retained in the majority of people with T1D and IAH, and that these changes can be detected by a wearable device. Real-time HRV seems usable for detection of hypoglycemia in patients with IAH.