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Effect of hypoglycemia on baroreflex sensitivity in individuals with type 2 diabetes: implications for autonomic control of cardiovascular function in diabetes

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Abstract

Purpose

Hypoglycemia is associated with increased mortality, though the mechanisms underlying this association are not established. Hypoglycemia impairs the counterregulatory hormonal and autonomic responses to subsequent hypoglycemia. It is unknown whether hypoglycemia elicits a generalized impairment in autonomic control of cardiovascular function in individuals with type 2 diabetes. We tested the hypothesis that in individuals with type 2 diabetes, hypoglycemia impairs a key measure of cardiovascular autonomic homeostasis, baroreflex sensitivity.

Methods

Sixteen individuals with well-controlled type 2 diabetes and without known cardiovascular disease were exposed to two 90-min episodes of experimental hypoglycemia (2.8 mmol/L, 50 mg/dL) on the same day. All individuals experienced a hypoglycemic-hyperinsulinemic clamp in the morning (AM clamp) and again in the afternoon (PM clamp). Baroreflex sensitivity was assessed using the modified Oxford method before the initiation of each hypoglycemic-hyperinsulinemic clamp, during the last 30 min of hypoglycemia, and the following morning. A mixed effects model adjusting for sex, age, BMI, and insulin level, demonstrated a significant effect of hypoglycemia on baroreflex sensitivity. The study is registered at ClinicalTrials.gov (NCT03422471).

Results

Baroreflex sensitivity during PM hypoglycemia was reduced compared to baseline, during AM hypoglycemia, and the next day. Insulin levels positively correlated with baroreflex sensitivity at baseline and during AM hypoglycemia.

Conclusion

Exposure to hypoglycemia impairs a key measure of autonomic control of cardiovascular function and, thus, may increase the risk of cardiac arrhythmias and blood pressure lability in individuals with type 2 diabetes. This effect is attenuated in part by increased insulin levels.

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Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

Bausch Health provided the nitroprusside for this study. This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (NCRR and NCATS, NIH Award UL1 TR001102), and the following grants from the NIH: K23HL155076 (AVH), K24HL103845 (GKA), R01HL111465-02 (RF), R01HL109634-02 (RF).

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Author notes

  1. Roy Freeman and Gail K. Adler have contributed equally.

Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA

    Andrea V. Haas, Andrew Koefoed, Rebecca M. Easly, Johanna Celli, Mahyar Heydarpour & Gail K. Adler

  2. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Istvan Bonyhay & Roy Freeman

Authors
  1. Andrea V. Haas
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  2. Andrew Koefoed
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  6. Istvan Bonyhay
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  7. Roy Freeman
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  8. Gail K. Adler
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Corresponding author

Correspondence to Andrea V. Haas.

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Conflict of interest

All authors have no financial or non-financial interests that are directly or indirectly related to the work.

Ethical approval

The institutional review boards at Brigham and Women’s Hospital and Beth Israel Deaconess Medical Center approved all study procedures, and all subjects gave written informed consent.

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Haas, A.V., Koefoed, A., Easly, R.M. et al. Effect of hypoglycemia on baroreflex sensitivity in individuals with type 2 diabetes: implications for autonomic control of cardiovascular function in diabetes. Clin Auton Res 33, 727–735 (2023). https://doi.org/10.1007/s10286-023-00983-5

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  • DOI: https://doi.org/10.1007/s10286-023-00983-5

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