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Effect of hypoglycemia on baroreflex sensitivity in individuals with type 2 diabetes: implications for autonomic
Andrea V Haas1, Andrew Koefoed2, Rebecca M Easly2
1Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA. ahaas2@bwh.harvard.edu.
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.
Insights
Hypoglycemia impairs baroreflex sensitivity, a measure of cardiovascular autonomic control, in people with type 2 diabetes. This effect may increase risks for blood pressure issues and arrhythmias, though insulin can offer some protection.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Diabetes Research
Background:
- Hypoglycemia is linked to higher mortality, but the mechanisms are unclear.
- Impaired counterregulatory responses to hypoglycemia are known.
- The impact of hypoglycemia on autonomic control of cardiovascular function in type 2 diabetes is not well understood.
Purpose of the Study:
- To investigate if hypoglycemia impairs baroreflex sensitivity in individuals with type 2 diabetes.
- To assess the effect of hypoglycemia on cardiovascular autonomic homeostasis.
Main Methods:
- Sixteen individuals with type 2 diabetes underwent two hypoglycemic-hyperinsulinemic clamp studies.
- Baroreflex sensitivity was measured using the modified Oxford method.
- Measurements were taken at baseline, during hypoglycemia, and the following morning.
Main Results:
- Baroreflex sensitivity was significantly reduced during afternoon hypoglycemia compared to baseline and morning hypoglycemia.
- Baroreflex sensitivity remained reduced the day after hypoglycemia.
- Higher insulin levels correlated with better baroreflex sensitivity.
Conclusions:
- Hypoglycemia impairs autonomic control of cardiovascular function in type 2 diabetes.
- This impairment may elevate the risk of cardiac arrhythmias and blood pressure lability.
- Increased insulin levels may partially mitigate these effects.
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