Effect of hypoxia on heart rate variability and baroreflex sensitivity during hypoglycemia in type 1 diabetes mellitus

Purpose: Patients with type 1 diabetes mellitus exhibit impairments in autonomic and cardiovascular control which are worsened with acute hypoglycemia––thus increasing the risk of adverse cardiovascular events. Hypoxia, as seen with the common comorbidity of sleep apnea, may lead to further autonomic dysfunction and an increased risk of ventricular arrhythmias. Therefore, we hypothesized that heart rate variability (HRV) and baroreflex sensitivity (BRS) would be reduced during hypoglycemia in adults with type 1 diabetes, with a further decline when combined with hypoxia. Methods: Subjects with type 1 diabetes (n = 13; HbA1c = 7.5 ± 0.3 %, duration of diabetes = 17 ± 5 yrs) completed two 180 min hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic (~3.3 µmol/mL) clamps separated by a minimum of 1 week and randomized to normoxia (S_pO₂ ~98 %) or hypoxia (S_pO₂ ~85 %). Heart rate (electrocardiogram) and blood pressure (finger photoplethysmography) were analyzed at baseline and during the hypoglycemic clamp for measures of HRV and spontaneous cardiac BRS (sCBRS). Results: Hypoglycemia resulted in significant reductions in HRV and sCBRS when compared with baseline levels (main effect of hypoglycemia: p < 0.05). HRV and sCBRS were further impaired during hypoxia (main effect of hypoxia: p < 0.05). Conclusions: Acute hypoxia worsens hypoglycemia-mediated impairments in autonomic and cardiovascular control in patients with type 1 diabetes and may increase the risk of cardiovascular mortality. These results highlight the potential cumulative dangers of hypoglycemia and hypoxia in this vulnerable population.