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      Diagnostic buccal d´une carence en vitamine B12 due à un traitement au long court avec le metformine: à propos d´un cas Translated title: Oral diagnosis of vitamin B12 deficiency due to long-term metformin treatment: a case report

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          Abstract

          Le metformine est actuellement placé en première ligne pour le traitement du diabète de type 2. Il est également indiqué dans le diabète de type 1 en cas de résistance à l´insuline. Il présente de nombreux effets bénéfiques sur le métabolisme des carbohydrates, la perte de poids et la protection vasculaire. Cependant, il peut également engendrer d´importants effets indésirables comme le risque d´anémie en cas d´utilisation prolongée. Il est rapporté que les patients sous metformine au long court présentent une réduction de la concentration sérique de la vitamine B12. Les signes buccaux associant une glossite de Hunter et une stomatodynie peuvent être révélateurs et conduire à un diagnostic précoce d´une carence en vitamine B12. Nous rapportons ici le cas d´une patiente qui présente ces signes buccaux depuis 2 ans et dont les bilans biologiques ont révélé une anémie normocytaire ferriprive avec carence en vitamine B12. La prise prolongée du metformine a été considérée comme étiologie de l´avitaminose B12 en attendant d´écarter d´autres causes probables. La correction par injection intramusculaire d´hydroxocobalamine avec du fer par voie orale ont permis la normalisation des taux sériques et la disparition des signes cliniques. La patiente a été adressée à un centre spécialisé pour un bilan étiologique plus poussé. Ce cas clinique met en relief le rôle important que peut jouer le médecin dentiste dans le diagnostic précoce de la déficience en vitamine B12 et la prévention de son évolution qui peut être dramatique en cas de découverte tardive.

          Translated abstract

          Metformin is the first line treatment for type 2 diabetes. It is also indicated in patients with insulin-resistant type 1 diabetes. It has several benefic effects on carbohydrate metabolism, weight loss and vascular protection. However, it can also cause serious adverse reactions such as the risk of anemia associated with long term use. It has been reported that long-term metformin use might reduce serum vitamin B12 levels. Oral signs combining Hunter glossitis and stomatodynia may be revelatory and lead to early diagnosis of vitamin B12 deficiency. We here report the case of a female patient who had had these oral signs for 2 years and whose laboratory tests revealed normocytic anemia with iron and vitamin B12 deficiency. The diagnosis of vitamin B12 deficiency due to long-term metformin was suspected while excluding other potential causes. Intramuscular hydroxocobalamin injection associated with oral iron led to the normalization of serum levels and to the disappearance of clinical signs. The patient was referred to a specialized center for further etiological assessment. This clinical case highlights the essential role of dentists in early diagnosis of vitamin B12 deficiency and the prevention of its progression, which can be dramatic in the case of late discovery.

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          Vitamin B12 Deficiency: Recognition and Management.

          Vitamin B12 deficiency is a common cause of megaloblastic anemia, various neuropsychiatric symptoms, and other clinical manifestations. Screening average-risk adults for vitamin B12 deficiency is not recommended. Screening may be warranted in patients with one or more risk factors, such as gastric or small intestine resections, inflammatory bowel disease, use of metformin for more than four months, use of proton pump inhibitors or histamine H2 blockers for more than 12 months, vegans or strict vegetarians, and adults older than 75 years. Initial laboratory assessment should include a complete blood count and serum vitamin B12 level. Measurement of serum methylmalonic acid should be used to confirm deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12. Oral administration of high-dose vitamin B12 (1 to 2 mg daily) is as effective as intramuscular administration for correcting anemia and neurologic symptoms. Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe neurologic symptoms. Absorption rates improve with supplementation; therefore, patients older than 50 years and vegans or strict vegetarians should consume foods fortified with vitamin B12 or take vitamin B12 supplements. Patients who have had bariatric surgery should receive 1 mg of oral vitamin B12 per day indefinitely. Use of vitamin B12 in patients with elevated serum homocysteine levels and cardiovascular disease does not reduce the risk of myocardial infarction or stroke, or alter cognitive decline.
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            Vitamin B12 Status in Metformin Treated Patients: Systematic Review

            Objective Randomized controlled trials and observational studies have yielded inconsistent results on the effects of metformin on vitamin B12 reduction. We therefore performed a systematic review to analyze the effects of metformin on vitamin B12 concentration. Methods PubMed, Medline, Embase, and the Cochrane central registry of controlled trials were searched to identify randomized controlled trials and observational studies exploring the association between metformin and vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. The main outcome measure was changes in serum vitamin B12 concentration after 6–208 weeks of treatment with metformin, as compared with placebo or other anti-hyperglycemic therapy. Results Six randomized controlled trials met the inclusion criteria. Serum vitamin B12 concentrations were significantly lower in patients treated with metformin than in those who received placebo or rosiglitazone (mean difference [MD], −53.93 pmol/L; 95% confidence interval [CI], −81.44 to −26.42 pmol/L, P = 0.0001). Subgroup analysis identified four trials in which patients received a lower dose of metformin (<2000 mg/d) and two in which they received a higher dose (≥2000 mg/d), with MDs in vitamin B12 concentration after metformin treatment of −37.99 pmol/L (95% CI, −57.44 to −18.54 pmol/L, P = 0.0001) and −78.62 pmol/L (95% CI, −106.37 to −50.86 pmol/L, P<0.00001), respectively. Conclusions The reduction of vitamin B12 may be induced by metformin in a dose dependent manner.
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              Prevalence of Vitamin B12 Deficiency in Patients with Type II Diabetes Mellitus on Metformin: A Study from Khyber Pakhtunkhwa

              Background Metformin is the most common oral hypoglycemic used and associated with certain abnormalities. The objective was to evaluate and define the occurrence and bases of vitamin B12 deficiency amongst patients on Metformin for diabetes mellitus type II. Methods A cross-sectional study was conducted on 209 patients having diabetes type II between January-December 2016. The patients aged > 45 years and who had taken metformin for at least three months were recruited with regular follow-up at the Endocrinology Unit of Hayatabad Medical Complex and Diabetic Center Hayatabad, Peshawar. The patients were included in a survey after which they had their serum B12 levels measured. Serum B12 levels < 150 pg/ml is defined as the B12 deficiency. Results About 29.66% of diabetic patients had confirmed the B12 insufficiency through laboratory tests. The patients on metformin had statistically lower values of B12 (P = 0.01). For the patients who smoked, vitamin B12 deficiency was significantly higher than those who did not smoke (p= <0.001). Also in patients using multivitamins, vitamin B12 deficiency was lower compared to nonusers (p=0.05). Conclusion Our study shows that for the patients with type 2 diabetes (T2DM), long-term treatment with metformin and smoking are associated with higher chances of developing vitamin B12 deficiency. Clinicians should, therefore, recognize this significant element and should screen diabetics who are on metformin treatment for any B12 insufficiency, which may be hidden, especially patients coming with neurologic symptoms. Additionally, multi vitamins taken daily may have a protective role.
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                Author and article information

                Journal
                Pan Afr Med J
                Pan Afr Med J
                PAMJ
                The Pan African Medical Journal
                The African Field Epidemiology Network
                1937-8688
                26 November 2020
                2020
                : 37
                : 280
                Affiliations
                [1 ]Environnement et Santé, Département de Biologie, Faculté des Sciences et Techniques d’Errachidia, Université Moulay Ismaïl de Meknès, Meknès, Maroc
                Author notes
                Corresponding author: Nourdine Attiya, Environnement et Santé, Département de Biologie, Faculté des Sciences et Techniques d’Errachidia, Université Moulay Ismaïl de Meknès, Meknès, Maroc. nourdineattiya@ 123456gmail.com
                Article
                PAMJ-37-280
                10.11604/pamj.2020.37.280.19776
                7864276
                eaff0cdd-15a3-43a4-9bd8-806db92d4d42
                Copyright: Nourdine Attiya et al.

                The Pan African Medical Journal (ISSN: 1937-8688). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 July 2019
                : 29 October 2020
                Categories
                Case Report

                Medicine
                metformine,vitamine b12,glossite de hunter,stomatodynie,case report,metformin,vitamin b12,hunter's glossitis,stomatodynia

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