title: Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin.
abstract: OBJECTIVE
  To investigate the associations of vitamin B12 (cobalamin and holotranscobalamin) status with depression, cognition and neuropathy in patients with type 2 diabetes using metformin.
  
  
  METHODS
  In an observational study, among 550 type 2 diabetes patients using metformin, cobalamin and holotranscobalamin (holoTCII) levels were measured at the annual diabetes checkup, and deficiencies were defined as <148 and <21 pmol/L, respectively. Depression and cognitive function were assessed with corresponding International Classification of Primary Care codes and questionnaires; neuropathy with medical record data and a questionnaire. Confounding variables were retrieved from medical records. Multivariable logistic and linear regressions were used with cobalamin status as independent variable; depression, cognition and neuropathy as dependent variables.
  
  
  RESULTS
  The mean duration of diabetes was 8.4 years (±5.8); mean duration of metformin use was 64.1 months (±43.2), with a mean metformin dose of 1,306 mg/day. A sufficient cobalamin level was independently associated with a decreased risk of depression (OR 0.42; 95 % CI 0.23-0.78) and better cognitive performance (β = 1.79; 95 % CI 0.07-3.52) adjusted for confounders. This indicates that cobalamin-deficient patients had a 2.4 times higher chance of depression and a 1.79 point lower cognitive performance score. HoloTCII was not associated with any outcome.
  
  
  CONCLUSIONS
  Cobalamin deficiency was associated with an increased risk of depression and worse cognitive performance, while holoTCII was not. Screening for cobalamin deficiency may be warranted in diabetes patients using metformin. Physicians should consider a cobalamin deficiency in diabetes patients using metformin with a depression or cognitive decline.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Elke
authors.initials: E
authors.lastname: Biemans
authors.forename: Huberta E
authors.initials: HE
authors.lastname: Hart
authors.forename: Guy E H M
authors.initials: GE
authors.lastname: Rutten
authors.forename: Viviana G
authors.initials: VG
authors.lastname: Cuellar Renteria
authors.forename: Antoinette M J
authors.initials: AM
authors.lastname: Kooijman-Buiting
authors.forename: Joline W J
authors.initials: JW
authors.lastname: Beulens
mesh_terms: D000328:Adult; D000368:Aged; D003071:Cognition; D003866:Depressive Disorder / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D003929:Diabetic Neuropathies / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use; D014805:Vitamin B 12 / Q000378:metabolism*; D014806:Vitamin B 12 Deficiency / Q000209:etiology* / Q000378:metabolism / Q000523:psychology
chemical_list: D008687:Metformin; D014805:Vitamin B 12