Abstract
Long term administration of metformin interferes with the absorption of vitamin B12 resulting in vitamin B12 deficiency.Among the various genetic variants that are associated vitamin B12 deficiency, we analyzed BHMT gene polymorphism and their association with metformin induced vitamin B12 deficiency in T2DM patients.A cross sectional study was done with 300 participants. Methyl malonic acid, homocysteine and high sensitive C reactive protein were analysed by Mass Spectrometry, Chemiluminescent analyser and Immunoturbidimetric method respectively. Genetic variants were analysed by ARMS-PCR method, Data was analyzed with various statistical tools like ROC, Odds ratio and Likelihood ratio. Significant reduction in folic acid and vitamin B12 in metformin users was found. High sensitive C reactive protein, homocysteine and methyl malonic acid are significantly increased in patients with metformin induced B12 deficiency. ‘A’ allele in BHMT (A allele OR =2.1, AA genotype =2.8) showed risk of vitamin B12 deficiency in T2DM patients on metformin therapy. BHMT gene polymorphism had LR of 2.65 for folic acid (AG genotype), 2.73 for MMA (AA genotype) and 2.63 for Homocysteine (AA genotype).We found an association between single nucleotide polymorphism of BHMT and diagnosis of vitamin B12 deficiency status in metformin users. Folic acid, MMA and homocysteine had high specificity in concordance with BHMT (rs3733890) polymorphism in predicting vitamin B12 deficiency. Early screening of SNP of BHMT in T2DM patients on metformin therapy will help us to identify group of people who are prone for vitamin B12 deficiency.
Highlights
B12 decreases with an increase in dosage and Type 2 diabetes mellitus (T2DM) rules worldwide, with the duration of administration of metformin.dietary intervention along with pharmacological [2] Metformin interferes with vitamin B12 treatment and regular monitoring of blood glucose absorption through the alterations in intestinal being the classical management
Fifty five percent of the vitamin B12 deficient group was receiving a dose of 1000mg/day of metformin, 39% were taking 1500mg/day and 6% were taking more than 2000mg/day of metformin
Among the 165 T2DM patients whose serum vitamin B12 levels were within the reference range, 93% were on metformin therapy for less than 5 years, 6% for 5 – 10 years and 1% of them were taking metformin for more than 10 years
Summary
Type 2 diabetes mellitus (T2DM) rules worldwide, with the duration of administration of metformin. Dietary intervention along with pharmacological [2] Metformin interferes with vitamin B12 treatment and regular monitoring of blood glucose absorption through the alterations in intestinal being the classical management. Metformin motility, increased bacterial overgrowth or remains the best treatment for T2DM alterations of vitamin B12-IF complex. A high deficiency is greatly influenced by the increase in degree of reciprocity occurs in the interrelationship age, metformin dosage, and its duration of use. Between different vitamins and Diabetes.[1]There Vitamin B12 (Cobalamin) plays a vital cofactor is an association between vitamin B12 deficiency role in the synthesis of DNA as well as in two and T2DM patients on metformin therapy. Vitamin B12 deficiency www.rspsciencehub.com prevalence varies from 5.8% to 30% among patients undergoing long-term treatment with metformin. Metformin induces vitamin B12 deficiency by binding its hydrophobic tail of biguanide to the hydrocarbon core of membranes
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