Vitamin B12 for Diabetes Patients Treated with Metformin

Metformin treatment, both duration and dose, is associated with increased risk of vitamin B12 (B12) deficiency. B12 deficiency causes Hyperhomocysteinemia (HHcy), which is associated with an increased risk of a variety of diabetic co-morbidities. As a result, the newest “Standards of Medical Care in Diabetes 2017”, issued by the American Diabetes Association included a recommendation to periodically assess B12 status and, as needed, utilize B12 replacement therapy among diabetes patients receiving metformin. Routine screening, using appropriate B12 assessment methods and interpretation, would enable providers to identify individuals with low B12 levels at an early stage. Prompt treatment with B12 injections or oral supplements may help in reducing the risk of low B12and HHcy-related sequelae and their associate medical cost. The assessment of B12 status and interpretation of results is not straightforward since several B12 assessment measures are available, including serum/plasma B12, Mean Corpuscular Volume, Homocysteine, Holotranscobalamin II and Methylmalonic Acid. The goal of this manuscript is to 1) Describe available B12 assessment methods including their advantages and disadvantages, 2) Interpret laboratory results of B12 biomarkers, and 3) Discuss available B12 deficiency treatment options. Routine screening, when appropriate B12 status analyses are performed and interpreted, would enable physicians to identify individuals with low B12 at early stage. Treatment with B12 injections or supplements would help in reducing risk of low B12 and HHcy-related symptoms. Such practice would reduce pain and suffering of diabetic patients. It would also decrease medical cost associated with treatments of diabetic co-morbidities. Review ARticle tiated at the time of diabetes diagnoses [1]. Metformin is also recommended for individuals with impaired fasting glucose and/or impaired glucose tolerance who also meet any of the following criteria: are < 60-years-old, have BMI ≥ 35 kg/m2, have a family history of diabetes in the first degree of relatives, have elevated triglycerides, have reduced HDL cholesterol, have hypertension, and have hemoglobin A1c > 6.0% [2]. Although metformin is effective in blood glucose control its use is associated with reduced vitamin B12 (B12) concentrations. Results of a recent meta-analysis based on 29 studies with 8,089 participants showed that patients receiving metformin therapy had 2.45 (95% CI 1.74-3.44, p < 0.0001) times higher odds of developing B12 deficiency in comparison to the non-metformin users [3]. There was a mean of 65.8 pmol/L (95% CI 53.6-78.1, p < 0.0001) reduction in the serum B12 level among patients receiving metformin compared to those not receiving metformin treatment. The above results are consistent with the findings published in a systemic review of the impact of metformin on B12 status by Liu, et al. [4]. They found that patients receiving metformin had statistically significantly lower serum B12 concentrations, compared to patients receiving placebo and/or Rosiglitazone (mean difference = 53.93 pmol/L, 95% CI 26.42-81.44, p = 0.0001). The association between metformin use and serum B12 reduction was dose-dependent [4]. Based on available evidence of the association between metformin use and reduced B12 levels, the newly published American Diabetes Association’s “Standards of Medical Care in Diabetes 2017” included a recommendation to periodically assess B12 status and, Introduction According to the recommendation issued jointly by the American Diabetes Association and the European Association for the Study of Diabetes, concurrently with lifestyle intervention, metformin therapy should be iniISSN: 2469-5793 DOI: 10.23937/2469-5793/1510057 Pawlak. J Fam Med Dis Prev 2017, 3:05T • Page 2 of 7 • and evidence-based deficiency cutoffs. Serum B12 along with MCV seem to be used the most in clinical settings. Unfortunately, these two assessment methods are not always accurate in making diagnoses of B12 status.