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 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 (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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Acknowledgments
The authors wish to acknowledge the contributions of the nursing and technical staff: Cheryl Shonkwiler, Barbara Norby, Shelly Roberts, Karen Krucker, Sarah Wolhart, Jean Knutson, Brent McConahey, Pamela Reich, Nancy Meyer, Pam Engrav, Christopher Johnson, and Kate Malterer of the Mayo Clinic. In addition, we thank the Clinical Research Unit staff at Mayo Clinic and the Immunochemical Core Laboratory at Mayo Clinic, in particular Hilary Blair. We are deeply indebted to our research participants. We thank Brandon Bucher and Brenton Nelson at AD Instruments for the development of the Spontaneous Cardiac Baroreflex Analysis Program. Funding sources: NIH DK090541 (MJJ, RB), NIH NS32352 (MJJ), NIH T32 DK07352 (JKL), NIH F32 HL120570 (JKL), NIH 1 UL1 RR024150 (Mayo Clinic CTSA, MJJ), and NIH DK29953 (RB).
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There are no relevant conflict of interest to disclose.
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R. Basu and M. J. Joyner share co-senior authorship.
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Limberg, J.K., Dube, S., Kuijpers, M. et al. Effect of hypoxia on heart rate variability and baroreflex sensitivity during hypoglycemia in type 1 diabetes mellitus. Clin Auton Res 25, 243–250 (2015). https://doi.org/10.1007/s10286-015-0301-2
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DOI: https://doi.org/10.1007/s10286-015-0301-2