Association Between Serum Neuron-specific Enolase Levels and Diabetic Neuropathy in Patients With Diabetes Mellitus: A Cross-sectional Study.

Introduction: Diabetic neuropathy is a common long-term complication among individuals with diabetes, affecting a significant portion of this population globally. Current diagnostic methods lack sensitivity for early detection and rely heavily on clinical examination, creating an urgent need for objective biomarkers. Neuron-specific enolase (NSE), a glycolytic enzyme specific to neurons, has emerged as a potential biomarker for neuronal damage across various neurological conditions.

Methods: This cross-sectional, hospital-based observational study was conducted at Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India, from May 2023 to October 2024. A total of 260 consecutive diabetic patients aged above 18 years were enrolled through systematic sampling from outpatient departments and inpatient wards. A comprehensive neurological assessment was performed using standardised Diabetic Neuropathy Symptom (DNS) and Diabetic Neuropathy Examination (DNE) scores by trained internal medicine physicians blinded to serum NSE levels. Each patient was independently assessed by two assessors, and inter-rater reliability was ensured through standardised training and assessed using Cohen's kappa and intraclass correlation coefficients. Serum NSE levels were measured using standardised immunoassay techniques. Statistical analysis was performed using the Chi-square test, independent samples t-test, correlation analysis, and ROC curve analysis with SPSS software, and a p-value of less than 0.05 was considered statistically significant.

Results: Among the 260 patients studied, males accounted for 45.8% and females for 54.2%. The mean age was 54.2 ± 9.7 years, with Type 2 diabetes predominant in 75.8% of cases. Diabetic neuropathy was present in 134 patients (51.5%), with peripheral neuropathy in 79 patients (30.4%) and autonomic neuropathy in 72 patients (27.7%). Only 17 patients (6.5%) had both types of neuropathy. Patients with peripheral neuropathy demonstrated significantly higher serum NSE levels (9.18 ± 1.43 ng/mL) compared to those without peripheral neuropathy (6.83 ± 1.52 ng/mL, p<0.001). In contrast, no significant difference was observed for autonomic neuropathy (7.56 ± 1.86 vs 7.54 ± 1.84 ng/mL, p=0.941). NSE demonstrated excellent discriminatory power for peripheral neuropathy with an area under the curve (AUC) of 0.863 (95% CI: 0.815-0.910) but poor performance for autonomic neuropathy with an AUC of 0.503. The optimal cutoff of 8.45 ng/mL yielded 67.1% sensitivity and 83.4% specificity. Exceptional correlations were observed between NSE and clinical assessment scores, with DNE score showing rs=0.937 (p<0.001) and DNS score showing rs=0.514 (p<0.001). NSE levels showed strong correlations with diabetes duration (r=0.4900, p<0.001) and glycemic control parameters, including HbA1c (r=0.3182, p<0.001).

Conclusion: The present study demonstrated that serum NSE serves as a highly effective biomarker for diabetic peripheral neuropathy with excellent diagnostic performance that meets international clinical standards. The strong correlations with established clinical measures and metabolic parameters, combined with its specific association with peripheral rather than autonomic neuropathy, support its potential clinical utility for early detection, risk stratification, and monitoring of diabetic neuropathy.