Impact of HbA1c variability and time-in-range fluctuations on large and small nerve fiber dysfunction in well-controlled type 2 diabetes: A prospective cohort observational study.

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).

Materials and methods: 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.

Results: 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.

Conclusions: 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.