Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands.
Diabetologia. 2013 Jun;56(6):1436-43. doi: 10.1007/s00125-013-2848-6. Epub 2013 Feb 13.
AIMS/HYPOTHESIS: We examined the effects of serum insulin levels on vagal control over the heart and tested the hypothesis that higher fasting insulin levels are associated with lower vagal control. We also examined whether experimentally induced increases in insulin by beta cell secretagogues, including glucagon-like peptide-1 (GLP-1), will decrease vagal control.
Respiration and ECGs were recorded for 130 healthy participants undergoing clamps. Three variables of cardiac vagal effects (the root mean square of successive differences [rMSSD] in the interbeat interval of the heart rate [IBI], heart-rate variability [HRV] caused by peak-valley respiratory sinus arrhythmia [pvRSA], and high-frequency power [HF]) and heart rate (HR) were obtained at seven time points during the clamps, characterised by increasing levels of insulin (achieved by administering insulin plus glucose, glucose only, glucose and GLP-1, and glucose and GLP-1 combined with arginine).
Serum insulin level was positively associated with HR at all time points during the clamps except the first-phase hyperglycaemic clamp. Insulin levels were negatively correlated with variables of vagal control, reaching significance for rMSSD and log10HF, but not for pvRSA, during the last four phases of the hyperglycaemic clamp (hyperglycaemic second phase, GLP-1 first and second phases, and arginine). These associations disappeared when adjusted for age, BMI and insulin sensitivity. Administration of the beta cell secretagogues GLP-1 and arginine led to a significant increase in HR, but this was not paired with a significant reduction in HRV measures.
CONCLUSION/INTERPRETATION: Experimentally induced hyperinsulinaemia is not correlated with cardiac vagal control or HR when adjusting for age, BMI and insulin sensitivity index. Our findings suggest that exposure to a GLP-1 during hyperglycaemia leads to a small acute increase in HR but not to an acute decrease in cardiac vagal control.
目的/假设：我们研究了血清胰岛素水平对心脏迷走神经控制的影响，并检验了以下假设，即空腹胰岛素水平较高与迷走神经控制较低有关。我们还研究了通过β细胞分泌激动剂（包括胰高血糖素样肽-1（GLP-1））人为增加胰岛素是否会降低迷走神经控制。
130 名健康参与者接受钳夹时记录呼吸和心电图。在钳夹过程中的七个时间点获得三个心脏迷走神经效应变量（心率间期的均方根差（rMSSD），由峰值-谷值呼吸窦性心律失常（pvRSA）引起的心率变异性（HRV）和高频功率（HF））和心率（HR），这些时间点的特点是胰岛素水平逐渐升高（通过给予胰岛素加葡萄糖、仅葡萄糖、葡萄糖和 GLP-1 以及葡萄糖和 GLP-1 与精氨酸联合实现）。
除第一相高血糖钳夹外，在钳夹过程中的所有时间点，血清胰岛素水平与 HR 呈正相关。胰岛素水平与迷走神经控制的变量呈负相关，在高血糖钳夹的后四个阶段（高血糖第二阶段、GLP-1 第一和第二阶段以及精氨酸），rMSSD 和 log10HF 达到显著水平，但 pvRSA 未达到显著水平。当调整年龄、BMI 和胰岛素敏感性时，这些关联消失。给予β细胞分泌激动剂 GLP-1 和精氨酸会导致 HR 显著增加，但这与 HRV 测量值的显著降低无关。
结论/解释：在调整年龄、BMI 和胰岛素敏感性指数后，实验性高胰岛素血症与心脏迷走神经控制或 HR 不相关。我们的研究结果表明，在高血糖期间暴露于 GLP-1 会导致 HR 出现短暂的急性增加，但不会导致心脏迷走神经控制的急性降低。
