ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Clinical Diabetes
This article is part of the Research TopicFrontiers in Diagnostic and Therapeutic approaches in Diabetic Sensorimotor Neuropathy, Volume IIView all 6 articles
From Glycemic Instability to Neuropathic Risk: A Propensity Score-Matched Retrospective Cohort Study
Provisionally accepted
Chong Yan
Yang Wang*- Hubei Provincial Third People's Hospital (Zhongshan Hospital), Wuhan, China
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Background: Despite glycemic control, many type 2 diabetes (T2DM) patients develop diabetic peripheral neuropathy (DPN), suggesting roles beyond HbA1c, such as glycemic variability (GV). Objective: To investigate whether GV is independently associated with DPN and explore potential mediation by inflammation and neurotrophic factors. Methods: This retrospective cohort included hospitalized T2DM patients with complete continuous glucose monitoring and nerve conduction studies. Propensity score matching balanced confounders. GV was assessed via MAGE and CV; DPN severity via composite NCV Z-score. Inflammatory (IL-6, TNF-α) and neurotrophic (NGF, IGF-1) markers were measured in a subcohort. Results: After matching (n=256), GV was significantly higher in DPN patients (all P<0.001). Higher GV correlated with worse NCV in a dose-response manner (P<0.001). Elevated IL-6/TNF-α and reduced NGF were associated with higher GV (P<0.05). MAGE and CV independently predicted worse NCV after adjustment (β=-0.38 & -0.31, P<0.001). Inflammation mediated ~32% of GV's effect on NCV (P<0.001). GV thresholds for DPN were MAGE≥5.8 mmol/L (AUC=0.84) and CV≥32.5% (AUC=0.81). Conclusion: Glycemic variability is independently associated with DPN presence and severity in T2DM, beyond HbA1c, partially mediated by inflammation. Incorporating GV assessment may improve DPN risk stratification, and GV-lowering therapies could offer neuroprotective benefits.
Keywords: Continuous glucose monitoring, Diabetic peripheral neuropathy, Glycemic variability, Inflammation, Nerve conduction studies, Propensity score matching
Received: 12 Dec 2025; Accepted: 04 Feb 2026.
Copyright: © 2026 Yan and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yang Wang
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