title: Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin.
abstract: BACKGROUND
  Hyperhomocysteinemia and vitamin B12 deficiency may be involved in the development of diabetic peripheral neuropathy (DPN). Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN.
  
  
  OBJECTIVE
  The purposes of this cross-sectional study were to assess (1) the potential associations of DPN with serum levels of homocysteine (tHcy), B-vitamins, and/or the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation; (2) the influence of chronic treatment with metformin on tHcy and B-vitamins concentrations and, finally, (3) to evaluate whether, by this influence, metformin is a risk factor for DPN in a group of type 2 diabetic outpatients.
  
  
  RESULTS
  Our data showed that fasting tHcy, folate, and vitamin B12 levels and the MTHFR C677T genotype distribution were comparable between subjects with (n = 79, 30 %) and without DPN (n = 184, 70 %). Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P < 0.001), but the prevalence of DPN was not different when compared to those not treated with this drug (33 vs. 27 %, P = NS). At univariate regression analysis, DPN was associated with age, duration of diabetes, HbA1c, creatinine levels, and the presence of coronary heart disease (CHD), and negatively with HDL-C concentrations (P < 0.05 all), but at multivariate regression analysis, high creatinine levels (P = 0.06), low HDL-C levels (P = 0.013), and a higher prevalence of CHD (P = 0.001) were the only variables independently associated with DPN in this population.
  
  
  CONCLUSIONS
  In conclusion, in these type 2 diabetic outpatients circulating levels of tHcy, folate, and the MTHFR C677T mutation are not associated with DPN, which was predicted by creatinine levels, CHD, and dyslipidemia. Metformin therapy is associated with a mild vitamin B12 level reduction, but not with DPN.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. giuseppina.russo@unime.it.
authors.forename: G T
authors.initials: GT
authors.lastname: Russo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giandalia
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: E L
authors.initials: EL
authors.lastname: Romeo
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Scarcella
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Gambadoro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Zingale
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Forte
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Perdichizzi
authors.affiliation: Department of Economical, Business and Environmental Sciences and Quantitative Methods, University of Messina, Messina, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Alibrandi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cucinotta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005500:Follow-Up Studies; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010045:Outpatients; D011379:Prognosis; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D007004:Hypoglycemic Agents; D006710:Homocysteine; D008687:Metformin; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12
keywords: Diabetic neuropathy; Homocysteine; MTHFR; Metformin; Type 2 diabetes; Vitamin B12