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Abstract: Aim: To explore the relationship between plasma total homocysteine concentration and diabetic neuropathy in Chinese patients with type 2 diabetes. Methods: Chinese patients with type 2 diabetes (n =249) were enrolled in a cross-sectional hospital based study. Diabetic neuropathy status was documented by presence of clinical signs and confirmed by electromyography. Plasma total homocysteine concentration was measured using fluorescence polarization immunoassay. Traditional risk factors for diabetic neuropathy were obtained from fasting blood samples and interviewer-questionnaire. Results: Plasma total homocysteine levels were higher in subjects with diabetic neuropathy than without (12.8 (9.2–14.8)μmol/l vs. 8.0 (7.7–9.1)μmol/l, p =0.005). The association of homocysteine with diabetic neuropathy was independent of major traditional risk factors for diabetic neuropathy (duration of diabetes, HbA1c) and determinants of higher homocysteine concentration (age, gender, serum folate and vitamin B12, renal status, and Biguanide use) (OR: 1.12 (1.00–1.25), p =0.042). Furthermore, per increase of 4.0μmol/l plasma homocysteine was related to neuropathy, after controlling for per unit increase of other factors (OR: 1.17 (0.94–1.33), p =0.045). Conclusion: Plasma total homocysteine concentration was independently associated with occurrence of diabetic neuropathy in Chinese people. Future prospective studies are warranted to clarify the relationship. [Copyright &y& Elsevier]