To investigate the associations of vitamin B12 (cobalamin and holotranscobalamin) status with depression, cognition and neuropathy in patients with type 2 diabetes using metformin.
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.
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.
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.
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Conflict of interest
Elke Biemans, Huberta E. Hart, Guy E.H.M. Rutten, Viviana G. Cuellar Renteria, Antoinette M.J. Kooijman-Buiting and Joline W. J. Beulens declare that they have no conflict of interest.
Human and animal rights
The Medical Research Ethics Committee at the University Medical Center Utrecht reviewed a brief protocol of the study and decided that the Medical Research Involving Human Subject Act (WMO) did not apply on this study because it was conducted with routine health care data. Therefore, full protocol review was not required since data from this study were routine care data.
Informed consent from all patients in the study was not necessary.
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Biemans, E., Hart, H.E., Rutten, G.E.H.M. et al. Cobalamin status and its relation with depression, cognition and neuropathy in patients with type 2 diabetes mellitus using metformin. Acta Diabetol 52, 383–393 (2015). https://doi.org/10.1007/s00592-014-0661-4