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

**Authors:** Muhammad Toqeer, Masood Uz Zaman Babar, Aiza Bhatti, Shumaila Israr, Eman Masood, Farooq Ahmad Malik, Zunaira Rizwan, Abdul Ahad Mehboob

PMC · DOI: 10.7759/cureus.101955 · Cureus · 2026-01-20

## TL;DR

High homocysteine levels in type 2 diabetes patients are linked to more severe nerve damage, suggesting a potential biomarker for early detection.

## Contribution

Identifies plasma homocysteine as an independent predictor of peripheral neuropathy severity in T2DM patients.

## Key findings

- 34.5% of T2DM patients had elevated homocysteine levels (>15 μmol/L).
- Neuropathy prevalence increased with homocysteine levels, reaching 85.7% in those with severe elevation.
- Homocysteine showed a strong positive correlation with neuropathy severity (r = 0.42, p < 0.001).

## Abstract

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.

## Linked entities

- **Chemicals:** homocysteine (PubChem CID 778)
- **Diseases:** type 2 diabetes mellitus (MONDO:0005148), peripheral neuropathy (MONDO:0003620)

## Full-text entities

- **Genes:** MTR (5-methyltetrahydrofolate-homocysteine methyltransferase) [NCBI Gene 4548] {aka HMAG, MS, cblG}
- **Diseases:** Hypertension (MESH:D006973), degeneration and demyelination (MESH:D003711), diabetic complications (MESH:D048909), impaired mobility (MESH:D014086), nerve damage (MESH:D000080902), infections (MESH:D007239), diabetic neuropathy (MESH:D003929), cardiovascular disease (MESH:D002318), ischemic damage (MESH:D017202), vascular damage (MESH:D057772), loss of sensation (MESH:D006987), vascular dysfunction (MESH:D002561), NCV (MESH:C564269), T2DM (MESH:D003924), depression (MESH:D003866), kidney disease (MESH:D007674), progressive neuropathy (MESH:D018450), hyperhomocysteinemia (MESH:D020138), tingling (MESH:D010292), DPN (MESH:D010523), type 1 diabetes (MESH:D003922), foot ulcers (MESH:D016523), Neuropathy (MESH:D009422), inflammation (MESH:D007249), hyperlipidemia (MESH:D006949), hyperglycemia (MESH:D006943), pain (MESH:D010146), dyslipidemia (MESH:D050171), neural damage (MESH:D015441), neurotoxic (MESH:D020258), Diabetes (MESH:D003920), endothelial dysfunction (MESH:D014652), chronic kidney disease (MESH:D051436), gestational diabetes (MESH:D016640), falls (MESH:C537863), vitamin B12 deficiency (MESH:D014806), overweight (MESH:D050177), axonal loss (MESH:D012183)
- **Chemicals:** DPN (-), amino acid (MESH:D000596), Homocysteine (MESH:D006710), vitamin B12 (MESH:D014805), dopamine (MESH:D004298), alcohol (MESH:D000438), serotonin (MESH:D012701), folic acid (MESH:D005492), methionine (MESH:D008715), oxygen (MESH:D010100), AGEs (MESH:D017127), metformin (MESH:D008687)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12921423/full.md

## References

19 references — full list in the complete paper: https://tomesphere.com/paper/PMC12921423/full.md

---
Source: https://tomesphere.com/paper/PMC12921423