A new study published in theFrontiers in Endocrinologyrevealed that higher blood levels of lactate dehydrogenase (LDH) are significantly associated with an increased risk of diabetic peripheral neuropathy (DPN) among individuals with type 2 diabetes mellitus (T2DM). The findings suggest that LDH could emerge as a practical biomarker for identifying diabetic patients at greater risk of developing nerve damage. The study was conducted on 2,060 adults diagnosed with T2DM and examined the potential relationship between serum LDH concentrations and the prevalence of DPN. DPN is characterized by nerve injury, often manifesting as pain, numbness, or loss of sensation in the extremities. It is believed to result from chronic metabolic disturbances and low-grade inflammation associated with prolonged hyperglycemia. This research utilized logistic regression models to evaluate both linear and non-linear trends between LDH levels and neuropathy risk. Restricted cubic spline (RCS) analyses were also performed to detect threshold effects, while subgroup analyses were conducted based on age, sex, hypertension, and glycemic control (HbA1c levels). Of the total participants, 724 (35.1%) were identified as having DPN. The data showed that serum LDH levels were independently correlated with neuropathy risk even after adjusting for other influencing factors such as age, body mass index, blood pressure, duration of diabetes, and lipid levels. For every 1 U/L increase in LDH, the adjusted odds ratio (OR) for DPN rose modestly (adjusted OR per 1 U/L: 1.00; 95% CI: 1.00–1.01; P = 0.01). The RCS model revealed that the association between LDH and DPN was not uniform across all values. A critical threshold was identified at 142 U/L. Beyond this point, the risk of neuropathy increased sharply. The participants with LDH levels exceeding 142 U/L were 21% more likely to have DPN (adjusted OR: 1.21; 95% CI: 1.02–1.48; P = 0.033) when compared to the individuals with lower enzyme concentrations. This relationship remained consistent across all subgroups, regardless of age, gender, blood pressure status, or glycemic control, strengthening the reliability of the findings. Overall, these results suggest that LDH could serve as an early indicator of metabolic stress and nerve injury in diabetic patients. Given its accessibility, clinicians might incorporate LDH monitoring into regular diabetes management to help identify individuals at higher risk of neuropathy before symptoms progress. Sun, M., Wang, Z., Yan, X., Shen, H., Yang, H., Qi, Y., Gao, X., Huang, Y., & Sun, J. (2025). Relationship between serum LDH levels and diabetic peripheral neuropathy in type 2 diabetic patients. Frontiers in Endocrinology, 16(1680539).https://doi.org/10.3389/fendo.2025.1680539