Li Siqi, Shan Xiangxiang, Wei Xing, Dai Wu, Cao Yonghong
Department of Endocrinology and Metabolism, The Second People's Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, 230011, Anhui, China.
The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, 230032, Anhui, China.
Diabetol Metab Syndr. 2025 Jun 9;17(1):201. doi: 10.1186/s13098-025-01794-6.
Diabetes has emerged as the third most significant global public health challenge. Among patients with type 2 diabetes mellitus (T2DM), cardiovascular autonomic neuropathy (CAN) represents a prevalent yet frequently overlooked complication. Hypoglycemia unawareness (HU) poses a persistent challenge in glycemic management for T2DM patients, yet its relationship with CAN remains inadequately understood. The aim of this study was to explore the correlation between HU and CAN through a prospective cohort study to provide a basis for early screening and intervention of CAN.
This study was a prospective cohort study, which finally included 223 T2DM patients who were admitted to the Department of Endocrinology of Hefei Hospital of Anhui Medical University from December 2020 to December 2024.Based on the subgroups with and without HU, Kaplan-Meier survival analysis model was constructed to clarify the variability of new-onset CAN between groups, and the log-rank test was used to assess the differences between groups. And further landmark analysis was performed on the survival curves. The correlation between HU and CAN was assessed using the COX proportional risk model with the no hypoglycemia group as the reference group.
Among the 223 patients analyzed, 143 (64.1%) subsequently developed CAN. Compared to those without CAN, patients in the CAN group exhibited significantly higher rates of diabetic peripheral neuropathy (DPN), a history of stroke, and smoking, alongside increased glycemic variability (SD). The incidence of new-onset CAN was markedly higher in the hypoglycemia unawareness group than in the non-hypoglycemia group. COX regression analysis revealed that HU is an independent risk factor for CAN in T2DM patient. Subgroup analyses and sensitivity analyses further validated the results.
The HU is an independent risk factor for CAN in patients with T2DM, and the effect of HU on CAN is more pronounced with the prolongation of the disease course. Early screening and intervention for CAN should be carried out in patients with HU in order to reduce the death rate associated with CAN.
The online version contains supplementary material available at 10.1186/s13098-025-01794-6.
糖尿病已成为全球第三大重要的公共卫生挑战。在2型糖尿病（T2DM）患者中，心血管自主神经病变（CAN）是一种常见但常被忽视的并发症。低血糖无意识（HU）在T2DM患者的血糖管理中始终是一个挑战，但其与CAN的关系仍未得到充分理解。本研究的目的是通过前瞻性队列研究探讨HU与CAN之间的相关性，为CAN的早期筛查和干预提供依据。
本研究为前瞻性队列研究，最终纳入2020年12月至2024年12月在安徽医科大学附属合肥医院内分泌科住院的223例T2DM患者。基于有无HU的亚组，构建Kaplan-Meier生存分析模型以阐明各组新发CAN的变异性，并使用对数秩检验评估组间差异。并对生存曲线进行进一步的标志性分析。以无低血糖组为参照组，采用COX比例风险模型评估HU与CAN的相关性。
在分析的223例患者中，143例（64.1%）随后发生了CAN。与未发生CAN的患者相比，CAN组患者的糖尿病周围神经病变（DPN）、中风病史和吸烟率显著更高，同时血糖变异性（SD）增加。低血糖无意识组新发CAN的发生率明显高于非低血糖组。COX回归分析显示，HU是T2DM患者发生CAN的独立危险因素。亚组分析和敏感性分析进一步验证了结果。
HU是T2DM患者发生CAN的独立危险因素，且随着病程延长，HU对CAN的影响更为明显。应针对有HU的患者进行CAN的早期筛查和干预，以降低与CAN相关的死亡率。
在线版本包含可在10.1186/s13098-025-01794-6获取的补充材料。
