Association between hypoglycemia unawareness and cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus: a prospective cohort study

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.