title: Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy.
abstract: The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients.
  
  
  
  In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency.
  
  
  
  Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman's rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3.88, P = 0.053).
  
  
  
  Close to third of metformin-treated T2DM patients had vitamin B12 deficiency. The deficiency was not associated with peripheral neuropathy. Black race was a protective factor for vitamin B12 deficiency.
authors.affiliation: Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa. mrwnwd@yahoo.com.
authors.forename: Marwan A
authors.initials: MA
authors.lastname: Ahmed
authors.affiliation: Department of Pharmacology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: George
authors.initials: G
authors.lastname: Muntingh
authors.affiliation: Department of Internal Medicine, Steve Biko Academic Hospital, University of Pretoria, Pretoria, South Africa.
authors.forename: Paul
authors.initials: P
authors.lastname: Rheeder
mesh_terms: D000368:Aged; D044383:Black People; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000097:blood / Q000453:epidemiology*; D015995:Prevalence; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000453:epidemiology*
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Diabetes; Metformin; Peripheral Neuropathy; Vitamin B12