Dataset Information

Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes.

ABSTRACT:

Background

Metformin can cause serum vitamin B12 deficiency, but studies on the influence of its duration and dose are lacking. We investigated vitamin B12 deficiency in patients with type 2 diabetes using metformin, in conjunction with other related factors.

Method

This cross-sectional study included 1111 patients with type 2 diabetes who took metformin for at least 6 months. Serum vitamin B12 levels were quantified using a competitive-binding immunoenzymatic assay, and vitamin B12 deficiency was defined as serum B12 <300?pg/mL. Information on metformin use and confounding variables were collected from records or questionnaires and interviews.

Result

Serum vitamin B12 deficiency occurred in 22.2% of patients (n?=?247). After adjusting for confounders, a 1?mg increase in daily metformin dose was associated with a 0.142?pg/mL decrease in vitamin B12 (P?ConclusionMetformin at ?1500?mg/d could be a major factor related to vitamin B12 deficiency, whereas concurrent supplementation of multivitamins may potentially protect against the deficiency. Serum homocysteine levels were negatively correlated with vitamin B12 levels, suggesting that B12 deficiency due to metformin use may occur at the tissue level. However, this hypothesis will require further study.

SUBMITTER: Kim J

PROVIDER: S-EPMC6867725 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes.

Kim Jiwoon J Ahn Chul Woo CW Fang Sungsoon S Lee Hye Sun HS Park Jong Suk JS

Medicine 20191101 46

<h4>Background</h4>Metformin can cause serum vitamin B12 deficiency, but studies on the influence of its duration and dose are lacking. We investigated vitamin B12 deficiency in patients with type 2 diabetes using metformin, in conjunction with other related factors.<h4>Method</h4>This cross-sectional study included 1111 patients with type 2 diabetes who took metformin for at least 6 months. Serum vitamin B12 levels were quantified using a competitive-binding immunoenzymatic assay, and vitamin B ...[more]

PMID: 31725641

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Project description:BackgroundThe association between prolong metformin usage and B12 deficiency has been documented. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed substantial disparity among studies due to varied study definitions of vitamin B12 deficiency. Metformin blocks the calcium dependent absorption of the vitamin B12-Intrinsic Factor complex at the terminal ileum. Lack of intrinsic factor due to the presence of auto-antibodies to parietal cells (IFA) could lead to vitamin B12 deficiency and subsequently cause peripheral neuropathy. We investigated the prevalence of vitamin B12 deficiency using more sensitive, combined markers of vitamin B12 status (4cB12) and the immuno-biochemical mediators of vitamin B12 deficiency.MethodsIn this observational study, 200 consecutive consenting metformin-treated T2DM patients, aged 35 and above, attending the diabetic clinic at KATH were recruited. Vitamin B12 deficiency was classified based on the Fedosov age-normalized wellness quotient. Anthropometric measurement was taken as well as blood samples for immunological and biochemical mediators. Peripheral neuropathy was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Statistical analysis was performed using the R Language for Statistical Computing.ResultsUsing the combined indicator (4cB12), the prevalence of metformin induced vitamin B12 deficiency was 40.5% whilst the prevalence of MNSI-Q and MNSI-PE diabetic neuropathy was 32.5% and 6.5% respectively. Participants with vitamin B12 deficiency had significantly higher levels of IFA, GPA, TNF-α, TC, LDL and albumin compared to those with normal vitamin B12 levels (p < 0.05). Correlation analysis revealed a statistically significant negative association between 4cB12 and the immunological markers [IFA (rs = -0.301, p<0.0001), GPA (rs = -0.244, p = 0.001), TNF-α (rs = -0.242, p = 0.001) and IL-6 (rs = -0.145, p = 0.041)]. Likewise, 4cB12 was negatively associated with TC (rs = -0.203, p = 0.004) and LDL (rs = -0.222, p = 0.002) but positively correlated with HDL (rs = 0.196, p = 0.005).ConclusionVitamin B12 deficiency and diabetic neuropathy are very high among metformin-treated T2DM patients and it is associated with increased GPA, IFA, TNF-α and cardiometabolic risk factors (higher LDL and TC and lower HDL). Upon verification of these findings in a prospective case-control study, it may be beneficial to include periodic measurement of Vitamin B12 using the more sensitive combined indicators (4cB 12) in the management of patients with T2DM treated with metformin in Ghana.

Project description:BackgroundLike many developed nations, the prevalence of both older people and type-2 diabetes mellitus (T2DM) in Singapore is rising. This demographic shift predisposes the population to greater risks of both frailty and its complications that can be further aggravated by vitamin B12 deficiency -a highly prevalent associated variable that is potentially modifiable. Indeed, B12 deficiency adversely impacts the neuro-cognitive, haematological, and even the immune systems; jeopardizing our aspirations for successful aging. Despite this, many patients with T2DM in primary care remain unscreened due to a lack of clear guidelines for regular B12 screening. We therefore investigated the determinants of B12 deficiency in community-dwelling patients with T2DM, with the aim of profiling patients most in need of B12-deficiency screening.MethodsB12 deficiency was evaluated using a retrospective cross-sectional cohort of 592 primary-care patients with T2DM, recruited from 2008 to 2011 from a Polyclinic in Singapore.ResultsB12 deficiency (serum B12 < 150 pmol/L) was present in 164 (27.7%) patients and was associated with a higher "metformin daily dose" (OR = 2.79; 95% CI, 2.22-3.48, P < 0.001); "age ≥ 80 years" (OR = 2.86; 95% CI, 1.31-6.25, P = 0.008); "vegetarianism" (OR = 21.61; 95% CI, 4.47-104.44, P < 0.001); and "folate deficiency" (OR = 2.04; 95% CI, 1.27-3.28, P = 0.003). Conversely, "Prescribed B12 supplementation" was associated with a lower odds of B12 deficiency (OR = 0.37; 95% CI: 0.22-0.61, P < 0.001). The area under the receiver operating characteristic curve was 0.803 (95% CI: 0.765-0.842). "Metformin daily dose" correlated interchangeably with "Metformin 1-year cumulative dose" (r = 0.960; P < 0.01), and also associated linearly with "duration of diabetes" (B = 0.113, P < 0.0001). Independent of the duration of T2DM, 29.3% of the B12-deficient patients needed > 1 screening test before the detection of B12 deficiency.ConclusionsPrimary-care screening for B12 deficiency should be part of the annual laboratory review of patients with T2DM regardless of the duration of T2DM -especially when they are prescribed ≥ 1.5 g/day of metformin; ≥ 80 years old; vegetarian; and not prescribed B12 supplementation. Concurrent evaluation for associated folate (vitamin B9) deficiency is essential when addressing T2DM-associated B12 deficiencies. Current "Metformin daily dose" is an accurate proxy of both cumulative metformin exposure and duration of T2DM.

Dataset Information

Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes.

Background

Method

Result

Publications

Association between metformin dose and vitamin B12 deficiency in patients with type 2 diabetes.

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