Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA.
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Clin Auton Res. 2023 Dec;33(6):727-735. doi: 10.1007/s10286-023-00983-5. Epub 2023 Sep 21.
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.
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).
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.
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.
低血糖与死亡率增加有关，但这种关联的机制尚未确定。低血糖会损害随后低血糖时的激素和自主神经的代偿反应。目前尚不清楚低血糖是否会引起 2 型糖尿病个体心血管功能自主控制的普遍损害。我们检验了以下假说，即在 2 型糖尿病个体中，低血糖会损害心血管自主平衡的一个关键指标，即压力感受性反射敏感性。
16 名血糖控制良好且无已知心血管疾病的 2 型糖尿病个体在同一天内经历两次 90 分钟的实验性低血糖（2.8 mmol/L，50 mg/dL）。所有个体在上午（AM 钳夹）和下午（PM 钳夹）都经历了低血糖-高胰岛素钳夹。在开始每次低血糖-高胰岛素钳夹之前、低血糖的最后 30 分钟和次日早上，使用改良的牛津方法评估压力感受性反射敏感性。使用混合效应模型，根据性别、年龄、BMI 和胰岛素水平进行调整，结果显示低血糖对压力感受性反射敏感性有显著影响。该研究在 ClinicalTrials.gov（NCT03422471）注册。
与基线相比，PM 低血糖期间的压力感受性反射敏感性在 AM 低血糖期间和次日降低。胰岛素水平与基线和 AM 低血糖期间的压力感受性反射敏感性呈正相关。
暴露于低血糖会损害心血管功能自主控制的一个关键指标，因此可能会增加 2 型糖尿病个体发生心律失常和血压波动的风险。这种效应部分通过胰岛素水平的增加而减弱。
