Xiangxiang Shan,1,2 Shenhang Yao,1,2 Ben Hu,2,3 Chi Xu,1,2 Yonghong Cao,1,2 Wu Dai1,2 

1Department of Endocrinology, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China; 2The Fifth Clinical School of Medicine, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Cardiology, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China

Correspondence: Yonghong Cao, Department of Endocrinology, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China, Email fish1982cao@126.com Wu Dai, Department of Endocrinology, The Second People’s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University, Hefei, Anhui, 230011, People’s Republic of China, Email 2245012184@stu.ahmu.edu.cn

Purpose: To investigate the correlation between time in range (TIR) and the risk of cardiovascular autonomic neuropathy (CAN) development in patients with Type 2 diabetes mellitus (T2DM).
Patients and Methods: This prospective cohort study enrolled patients with type 2 diabetes mellitus (T2DM) hospitalized and followed at the Department of Endocrinology, Hefei Hospital of Anhui Medical University, between September 2020 and July 2024. All participants underwent standardized cardiovascular autonomic neuropathy (CAN) assessment via the Ewing test, and time in range (TIR) was derived from baseline continuous glucose monitoring (CGM) data. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CAN incidence, adjusted for relevant covariates.
Results: Over a median follow-up of 25.0 months, 123 of 196 participants (62.8%) were diagnosed with CAN. The CAN group exhibited longer diabetes duration, lower time in range (TIR) and body mass index (BMI), higher time above range (TAR), mean glucose (MG), urinary albumin-to-creatinine ratio (UACR), and higher insulin use rates. Participants with low TIR were older, had longer diabetes duration, and displayed: 1. Higher fasting plasma glucose (FPG), HbA1c, and LDL-C levels; 2. Elevated glycemic variability (MAGE, CV, LAGE, SD, MG, TAR) via continuous glucose monitoring (CGM); 3. Greater likelihood of insulin therapy. All differences were statistically significant (P < 0.05). Multivariable Cox regression analyses, adjusted for key covariates (eg, age, HbA1c, insulin use), demonstrated an inverse association between TIR and CAN incidence.
Conclusion: Lower TIR is an independent risk factor for CAN in T2DM patients, with higher TIR levels associated with reduced CAN risk (P < 0.05).

Keywords: time in range, cardiovascular autonomic neuropathy, type 2 diabetes, cohort study