Department of Medical Sciences, Clinical Diabetology and Metabolism, Uppsala University, 751 85 Uppsala, Sweden.
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University, 901 85 Umeå, Sweden.
Eur J Endocrinol. 2024 Oct 29;191(5):499-508. doi: 10.1093/ejendo/lvae130.
Previous research points to a role of the brain in the regulation of glucose and pathogenesis of type 2 diabetes (T2D) via modulation of counter-regulatory hormone secretion and activity in the autonomic nervous system (ANS). The aim of this study was to investigate glucose-dependent responses of catecholamines and ANS activity in individuals with T2D, prediabetes (PD), and normoglycemia (NG).
Cross-sectional.
Individuals with T2D (n = 19, 7 men, HbA1c 49 mmol/mol), PD (n = 18, 8 men), and NG (n = 17, 3 men) underwent 1 stepwise hyperinsulinemic-euglycemic-hypoglycemic and 1 hyperglycemic clamp with repeated measurements of catecholamines, symptoms, heart rate variability (HRV), and hemodynamics.
The hypoglycemic response of adrenaline was augmented in T2D and PD vs NG (both P < .05), and there was a strong association with insulin resistance (P < .05 for M-value). In relation to achieved glucose levels in both clamps, noradrenaline exhibited a steeper rise during hypoglycemia in T2D vs NG and PD (both P < .05). There were trends toward more marked autonomic hypoglycemic symptoms in T2D vs PD and NG. By contrast, insulin resistance was associated with attenuated responses of heart rate and HRV indices PLF and PHF at the target glucose plateau of 2.7 mmol/L (P < .05), independent of BMI and HbA1c.
Alterations in glucose-dependent responses of counter-regulatory hormones and the ANS appear before, and probably contribute to, the onset of T2D. Together with other reported alterations in neuroendocrine pathways, the findings suggest that a maladaptation of the brain's responses to glucose fluctuations is important in T2D progression.
先前的研究表明，大脑通过调节自主神经系统（ANS）中的代偿激素分泌和活性，在调节葡萄糖和 2 型糖尿病（T2D）发病机制方面发挥作用。本研究旨在探讨 T2D、前驱糖尿病（PD）和血糖正常（NG）个体中葡萄糖依赖性儿茶酚胺反应和 ANS 活性。
横断面研究。
T2D 患者（n=19，男性 7 人，HbA1c 49mmol/mol）、PD 患者（n=18，男性 8 人）和 NG 患者（n=17，男性 3 人）分别进行了 1 次逐步高胰岛素-正常血糖-低血糖和 1 次高血糖钳夹试验，重复测量儿茶酚胺、症状、心率变异性（HRV）和血液动力学。
T2D 和 PD 患者的低血糖反应中肾上腺素增加（均 P <.05），与胰岛素抵抗呈强相关（M 值 P <.05）。与两种钳夹中达到的血糖水平相关，去甲肾上腺素在 T2D 患者的低血糖反应中比 NG 和 PD 患者的上升更陡峭（均 P <.05）。T2D 患者与 PD 和 NG 患者相比，出现更明显的自主神经低血糖症状的趋势。相比之下，胰岛素抵抗与目标血糖 2.7mmol/L 平台时心率和 HRV 指数 PLF 和 PHF 的反应减弱相关（P <.05），与 BMI 和 HbA1c 无关。
在 T2D 发病前，代偿性激素和 ANS 的葡萄糖依赖性反应发生改变，并可能导致 T2D 发病。结合其他报道的神经内分泌途径的改变，这些发现表明大脑对葡萄糖波动反应的失调在 T2D 进展中很重要。
