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Metformin and Micronutrient Status in Type 2 Diabetes: Does Polypharmacy Involving Acid-Suppressing Medications Affect Vitamin B12 Levels?

ABSTRACT: Metformin is the first-choice drug in uncomplicated type 2 diabetes (T2DM) and is effective in improving glycaemic control. It is the most widely prescribed oral antidiabetic medicine and has a good safety profile. However, there is an abundance of evidence that metformin use is associated with decreased Vitamin B12 status, though the clinical implications of this in terms of increased risk of diabetic peripheral neuropathy are debated. There is growing evidence that other B vitamins, vitamin D and magnesium may also be impacted by metformin use in addition to alterations to the composition of the microbiome, depending on the dose and duration of therapy. Patients using metformin for prolonged periods may, therefore, need initial screening with intermittent follow-up, particularly since vitamin B12 deficiency has similar symptoms to diabetic neuropathy which itself affects 40-50% of patients with T2DM at some stage. Among patients with T2DM, 40% are reported to experience symptomatic gastroesophageal reflux disease (GORD), of whom 70% use oral antidiabetic medications. The most common medications used to treat GORD are proton pump inhibitors (PPIs) and antagonists of histamine selective H2 receptors (H2RAs), both of which independently affect vitamin B12 and magnesium status. Research indicates that co-prescribing metformin with either PPIs or H2RAs can have further deleterious effects on vitamin B12 status. Vitamin B12 deficiency related to metformin and polypharmacy is likely to contribute to the symptoms of diabetic neuropathy which may frequently be under-recognised. This review explores current knowledge surrounding these issues and suggests treatment strategies such as supplementation.

SUBMITTER: Wakeman M

PROVIDER: S-EPMC7308123 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Metformin and Micronutrient Status in Type 2 Diabetes: Does Polypharmacy Involving Acid-Suppressing Medications Affect Vitamin B12 Levels?

Wakeman Michael M Archer David T DT

Diabetes, metabolic syndrome and obesity : targets and therapy 20200618

Metformin is the first-choice drug in uncomplicated type 2 diabetes (T2DM) and is effective in improving glycaemic control. It is the most widely prescribed oral antidiabetic medicine and has a good safety profile. However, there is an abundance of evidence that metformin use is associated with decreased Vitamin B12 status, though the clinical implications of this in terms of increased risk of diabetic peripheral neuropathy are debated. There is growing evidence that other B vitamins, vitamin D ...[more]

PMID: 32606868

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Project description:PurposeAnticholinergic burden (ACB), the cumulative effect of anticholinergic medications, is associated with adverse outcomes in older people but is less studied in middle-aged populations. Numerous scales exist to quantify ACB. The aims of this study were to quantify ACB in a large cohort using the 10 most common anticholinergic scales, to assess the association of each scale with adverse outcomes, and to assess overlap in populations identified by each scale.MethodsWe performed a longitudinal analysis of the UK Biobank community cohort (502,538 participants, baseline age: 37-73 years, median years of follow-up: 6.2). The ACB was calculated at baseline using 10 scales. Baseline data were linked to national mortality register records and hospital episode statistics. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular event (MACE). Secondary outcomes were all-cause mortality, MACE, hospital admission for fall/fracture, and hospital admission with dementia/delirium. Cox proportional hazards models (hazard ratio [HR], 95% CI) quantified associations between ACB scales and outcomes adjusted for age, sex, socioeconomic status, body mass index, smoking status, alcohol use, physical activity, and morbidity count.ResultsAnticholinergic medication use varied from 8% to 17.6% depending on the scale used. For the primary outcome, ACB was significantly associated with all-cause mortality/MACE for each scale. The Anticholinergic Drug Scale was most strongly associated with mortality/MACE (HR = 1.12; 95% CI, 1.11-1.14 per 1-point increase in score). The ACB was significantly associated with all secondary outcomes. The Anticholinergic Effect on Cognition scale was most strongly associated with dementia/delirium (HR = 1.45; 95% CI, 1.3-1.61 per 1-point increase).ConclusionsThe ACB was associated with adverse outcomes in a middle- to older-aged population. Populations identified and effect size differed between scales. Scale choice influenced the population identified as potentially requiring reduction in ACB in clinical practice or intervention trials.

Project description:BackgroundVitamin B12 is an essential micronutrient in humans needed for health maintenance. Deficiency of vitamin B12 has been linked to dietary, environmental and genetic factors. Evidence for the genetic basis of vitamin B12 status is poorly understood. However, advancements in genomic techniques have increased the knowledge-base of the genetics of vitamin B12 status. Based on the candidate gene and genome-wide association (GWA) studies, associations between genetic loci in several genes involved in vitamin B12 metabolism have been identified.ObjectiveThe objective of this literature review was to identify and discuss reports of associations between single-nucleotide polymorphisms (SNPs) in vitamin B12 pathway genes and their influence on the circulating levels of vitamin B12.MethodsRelevant articles were obtained through a literature search on PubMed through to May 2017. An article was included if it examined an association of a SNP with serum or plasma vitamin B12 concentration. Beta coefficients and odds ratios were used to describe the strength of an association, and a P < 0.05 was considered as statistically significant. Two reviewers independently evaluated the eligibility for the inclusion criteria and extracted the data.ResultsFrom 23 studies which fulfilled the selection criteria, 16 studies identified SNPs that showed statistically significant associations with vitamin B12 concentrations. Fifty-nine vitamin B12-related gene polymorphisms associated with vitamin B12 status were identified in total, from the following populations: African American, Brazilian, Canadian, Chinese, Danish, English, European ancestry, Icelandic, Indian, Italian, Latino, Northern Irish, Portuguese and residents of the USA.ConclusionOverall, the data analyzed suggests that ethnic-specific associations are involved in the genetic determination of vitamin B12 concentrations. However, despite recent success in genetic studies, the majority of identified genes that could explain variation in vitamin B12 concentrations were from Caucasian populations. Further research utilizing larger sample sizes of non-Caucasian populations is necessary in order to better understand these ethnic-specific associations.

Dataset Information

Metformin and Micronutrient Status in Type 2 Diabetes: Does Polypharmacy Involving Acid-Suppressing Medications Affect Vitamin B12 Levels?

Publications

Metformin and Micronutrient Status in Type 2 Diabetes: Does Polypharmacy Involving Acid-Suppressing Medications Affect Vitamin B12 Levels?

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