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

Abstract

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 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-minute hyperinsulinemic (2 mU/kg TBW/min), hypoglycemic (~3.3 μmol/mL) clamps separated by a minimum of 1 week and randomized to normoxia (SpO2 ~98%) or hypoxia (SpO2 ~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.

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“…BRS describes the degree to which the heart rate increases or decreases in response to a given change in mean arterial pressure as a consequence of the baroreflex. In detailed experimental studies of participants with and without type 1 diabetes, BRS has been shown to fall during experimental hypoglycemia along with a resetting of the working range to higher heart rates ( 29 , 30 ). In patients with diabetes, a failure of baroreceptors to reset to higher heart rates could lead to an increase in vagal restraint in the face of sustained sympathetic stimulation, rising SBP, and pulse pressure because the operating point remains at baseline levels.…”