title: Study of Vitamin B12deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus.
abstract: BACKGROUND
  Long-term therapy with metformin was shown to decrease the Vitamin B12level and manifested as peripheral neuropathy.
  
  
  OBJECTIVE
  The aim of this study is to define the prevalence of Vitamin B12deficiency in early Type 2 diabetic patients (duration ≤5 years or drug treatment ≤3 years) and the relationship among metformin exposure and levels of cobalamin (Cbl), folic acid, and homocysteine (Hcy) with severity of peripheral neuropathy.
  
  
  METHODS
  This is a cross-sectional study involving randomly selected ninety patients (male 56, female 34) between age groups of 35 and 70 years, comparing those who had received >6 months of metformin (Group A) (n= 35) with those without metformin (Group B) (n= 35) and patients taking metformin with other oral hypoglycemic agent (Group C) (n= 20). Comparisons were made clinically, biochemically (serum Cbl, fasting Hcy, and folic acid), and with electrophysiological measures (nerve conduction studies of all four limbs). Comorbidities contributing to neuropathy were excluded from the study.
  
  
  RESULTS
  Group A patients (54.28%) were prone to develop peripheral neuropathy comparing Group B (28.57%) and Group C (35%). There was significantly low plasma level of Cbl in Group A (mean 306.314 pg/ml) than in Group B (mean 627.543 pg/ml) and Group C (mean 419.920 pg/ml). There was insignificant low-level plasma folic acid in Group A (16.47 ng/ml) than in Group B (16.81 ng/ml) and Group C (22.50 ng/ml). There was significantly high level of Hcy in Group A (mean 17.35 µmol/L) and Group C (mean 16.99 µmol/L) than in Group B (mean 13.22 µmol/L). Metformin users even for 2 years showed evidence of neuropathy on nerve conduction velocity though their body mass index and postprandial blood sugar were maintained. There was significant difference in between groups regarding plasma Cbl, folic acid, and Hcy level as significance level <0.05 in all three groups (F[2, 87] = 28.1,P= 0.000), (F[2, 87] = 7.43,P= 0.001), (F[2, 87] = 9.76,P= 0.000).Post hocstudy shows significant (P< 0.05) lowering of Cbl and Hcy level in Group A (mean = 306.314, standard deviation [SD] = 176.7) than in Group C (mean = 419.92, SD = 208.23) and Group B (mean = 627.543, SD = 168.33).
  
  
  CONCLUSIONS
  Even short-term treatment with metformin causes a decrease in serum Cbl folic acid and increase in Hcy, which leads to peripheral neuropathy in Type 2 diabetes patients. A multicenter study with heterogeneous population would have increased the power of the study. We suggest prophylactic Vitamin B12and folic acid supplementation or periodical assay in metformin user.
authors.affiliation: Department of Medicine, Vivekananda Hospital, Durgapur, West Bengal, India.
authors.forename: Rudra Prasad
authors.initials: RP
authors.lastname: Roy
authors.affiliation: Department of Medicine, Murshidabad Medical College, Berhampore, West Bengal, India.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Ghosh
authors.affiliation: Department of Medicine, Murshidabad Medical College, Berhampore, West Bengal, India.
authors.forename: Manas
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: Independent Public Health Consultant, Howrah, West Bengal, India.
authors.forename: Amitava
authors.initials: A
authors.lastname: Acharyya
authors.affiliation: Department of Medicine, Charnock Hospital, Kolkata, West Bengal, India.
authors.forename: Ambarish
authors.initials: A
authors.lastname: Bhattacharya
authors.affiliation: Department of Biochemistry, Burdwan Medical College and Hospital, Burdwan, West Bengal, India.
authors.forename: Mrinal
authors.initials: M
authors.lastname: Pal
authors.affiliation: Department of Medicine, College of Medicine and Sagore Dutta Hospital, Kolkata, West Bengal, India.
authors.forename: Sisir
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Department of Endocrinology, NRS Medical College, Kolkata, West Bengal, India.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Sengupta
keywords: Diabetes mellitus; Vitamin B12 deficiency; metformin; screening