Relationship Between Elevated Plasma Homocysteine Levels and Severity of Peripheral Neuropathy in Patients With Type 2 Diabetes Mellitus: A Cross-Sectional Analysis

Background Peripheral neuropathy is a common and debilitating complication of type 2 diabetes mellitus (T2DM). Objective To evaluate the relationship between plasma homocysteine levels and the severity of peripheral neuropathy in patients with T2DM. Methods A cross-sectional study was conducted at Sahiwal Teaching Hospital, Sahiwal, from November 2024 to July 2025, involving 325 patients with T2DM. Plasma homocysteine levels were measured, and peripheral neuropathy severity was assessed using the Michigan Neuropathy Screening Instrument (MNSI) and nerve conduction studies (NCS). Results Elevated plasma homocysteine levels (>15 μmol/L) were found in 34.5% of patients. The prevalence of neuropathy increased with higher homocysteine levels, with 44.5% of patients with normal homocysteine levels exhibiting neuropathy, compared to 66.7% in those with mild elevation and 85.7% in those with severe elevation. A positive correlation was observed between homocysteine levels and neuropathy severity (r = 0.42, p <0.001). Multivariate regression analysis identified homocysteine as an independent predictor of neuropathy severity (β = 0.38, p<0.001), along with diabetes duration and glycated hemoglobin (HbA1c). Conclusion Elevated plasma homocysteine levels are associated with increased severity of peripheral neuropathy in T2DM patients. These findings suggest that homocysteine may serve as a biomarker for identifying T2DM patients at risk for severe neuropathy, with potential implications for early diagnosis and therapeutic interventions.