Lai Yun-Ru, Chiu Wen-Chan, Cheng Ben-Chung, Yu I-Hsun, Lin Ting-Yin, Chiang Hui-Ching, Kuo Chun-En Aurea, Lu Cheng-Hsien
Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Department of Hyperbaric Oxygen Therapy Center, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
J Diabetes Investig. 2025 Aug;16(8):1507-1517. doi: 10.1111/jdi.70079. Epub 2025 May 21.
AIMS/INTRODUCTION: Glycemic variability (GV) is a critical factor in the development of diabetic sensorimotor polyneuropathy (DSPN). This study aimed to evaluate the association of long-term GV, measured by glycated hemoglobin (HbA1c) average real variability (ARV), and short-term GV, assessed by time-in-range (TIR) ARV, with large and small nerve fiber dysfunction in individuals with well-controlled Type 2 Diabetes (T2D).
A prospective study conducted at a tertiary hospital in Taiwan included 82 T2D participants. Long-term GV was assessed using HbA1c ARV from visit-to-visit measurements at three-month intervals over 1 year. Short-term GV was evaluated as TIR ARV from seven-day fingerstick data collected quarterly. Large and small nerve functions were assessed using the Toronto Clinical Neuropathy Score (TCNS), nerve conduction studies, quantitative thermal testing, and Sudoscan.
Linear regression analysis adjusted for age, diabetes duration, and renal function revealed strong correlations between HbA1c ARV, TIR ARV, and diabetes duration. At baseline, high HbA1c ARV and TIR ARV groups exhibited higher TCNS and composite nerve conduction amplitude scores but lower cold detection thresholds compared to the low median groups. At one-year follow-up, TCNS significantly increased in the high HbA1c ARV (P = 0.001) and TIR ARV (P = 0.003) groups compared to the low median groups.
Both long-term and short-term GV significantly contribute to small and large nerve fiber dysfunction in T2D, yielding similar neurological outcomes despite stable mean glucose levels. Combining GV minimization strategies with standard glycemic control may be essential in reducing DSPN risk.
目的/引言：血糖变异性（GV）是糖尿病感觉运动性多发性神经病变（DSPN）发生发展的关键因素。本研究旨在评估以糖化血红蛋白（HbA1c）平均实际变异性（ARV）衡量的长期GV以及以血糖在目标范围内时间（TIR）的ARV评估的短期GV与血糖控制良好的2型糖尿病（T2D）患者大、小神经纤维功能障碍之间的关联。
在台湾一家三级医院进行的一项前瞻性研究纳入了82名T2D参与者。长期GV通过1年内每隔3个月就诊时测量的HbA1c ARV进行评估。短期GV通过每季度收集的7天指尖血糖数据计算的TIR ARV进行评估。大、小神经功能使用多伦多临床神经病变评分（TCNS）、神经传导研究、定量热测试和Sudoscan进行评估。
经年龄、糖尿病病程和肾功能校正的线性回归分析显示，HbA1c ARV、TIR ARV与糖尿病病程之间存在强相关性。在基线时，与低中位数组相比，高HbA1c ARV和TIR ARV组的TCNS和复合神经传导幅度评分更高，但冷觉检测阈值更低。在1年随访时，与低中位数组相比，高HbA1c ARV组（P = 0.001）和TIR ARV组（P = 0.003）的TCNS显著升高。
长期和短期GV均对T2D患者的大、小神经纤维功能障碍有显著影响，尽管平均血糖水平稳定，但神经学结局相似。将GV最小化策略与标准血糖控制相结合可能对降低DSPN风险至关重要。
