Does Metformin Treatment in Pediatric Population Cause Vitamin B12 Deficiency?

Abstract

Background/Aim There have been no studies to date examining the effect of metformin treatment on vitamin B12 status in children and adolescents. In this prospective study, the effects of metformin on blood vitamin B12, serum methylmalonic acid (MMA), homocysteine and holo-transcobalamin-II (holo-TC-II) levels were assessed in pediatric age group.

Materials and Methods This prospective study was conducted at the Pediatric Endocrinology and Adolescent Department between January 2017 and March 2019. Metabolic syndrome and polycystic ovary syndrome diagnosed patients with insulin resistance and/or impaired glucose tolerance, patients with type 2 diabetes mellitus (DM) treated with metformin were enrolled in study. Blood vitamin B12, MMA, homocysteine, holo-TC-II levels and hemogram values were evaluated.

Results Twenty-four patients were enrolled in study. Among these, 15 (62.5%) were female. The mean age of patients was 13.7±2.3 (10–19) years. Sixteen patients were diagnosed with metabolic syndrome and 8 patients were type 2 DM. At 6-month follow-up of all patients, there was no statistically significant difference in terms of vitamin B12, homocysteine, MMA and holo-TC-II levels. A 0.6% decline in vitamin B12 levels were revealed. At 12-month follow-up of 11 patients (45.8%) (6 Type 2 DM, 5 metabolic syndrome), no statistically significant difference was determined in vitamin B12, homocysteine, MMA and holo-TC-II levels. There were 6% decline in vitamin B12 levels and 10.9% increase in homocysteine levels, 5.4% decrease was detected in holo-TC-II level.

Conclusion Although no significant changes in the serum vitamin B12, homocysteine, MMA or holo-TC-II levels with metformin therapy were detected, long-term prospective studies with high-dose metformin treatment in pediatric population are needed to confirm our results.

Zusammenfassung

Hintergrund Bislang gibt es keine Studien, die die Auswirkungen einer Metformin-Behandlung auf den Vitamin-B12-Status bei Kindern und Jugendlichen untersuchen. In dieser prospektiven Studie wurden die Auswirkungen von Metformin auf den Vitamin-B12-Spiegel im Blut, die Methylmalonsäure (MMA) im Serum, Homocystein und Holo-Transcobalamin-II (Holo-TC-II) in der pädiatrischen Altersgruppe untersucht.

Materialien und Methoden Diese prospektive Studie wurde zwischen Januar 2017 und März 2019 in der Abteilung für pädiatrische Endokrinologie und Jugendmedizin durchgeführt. An der Studie nahmen Patienten mit Metabolischem Syndrom und polyzystischem Ovarsyndrom teil, bei denen eine Insulinresistenz und/oder eine gestörte Glukosetoleranz diagnostiziert wurde, sowie Patienten mit Diabetes mellitus Typ 2 (DM), die mit Metformin behandelt wurden. Die Blutwerte von Vitamin B12, MMA, Homocystein, Holo-TC-II und das Blutbild wurden ausgewertet.

Ergebnisse Vierundzwanzig Patienten wurden in die Studie aufgenommen. Von ihnen waren 15 (62,5%) weiblich. Das Durchschnittsalter der Patienten betrug 13,7±2,3 (10–19) Jahre. Bei sechzehn Patienten wurde ein metabolisches Syndrom und bei 8 Patienten Typ-2-DM diagnostiziert. Bei der 6-monatigen Nachuntersuchung aller Patienten gab es keine statistisch signifikanten Unterschiede in Bezug auf die Vitamin-B12-, Homocystein-, MMA- und Holo-TC-II-Werte. Bei den Vitamin-B12-Werten wurde ein Rückgang um 0,6% festgestellt. Bei der 12-monatigen Nachbeobachtung von 11 Patienten (45,8%) (6 Typ-2-DM, 5 metabolisches Syndrom) wurde kein statistisch signifikanter Unterschied bei den Vitamin-B12-, Homocystein-, MMA- und Holo-TC-II-Werten festgestellt. Der Vitamin-B12-Spiegel sank um 6%, der Homocysteinspiegel stieg um 10,9% und der Holo-TC-II-Spiegel ging um 5,4% zurück.

Schlussfolgerung Obwohl keine signifikanten Veränderungen der Serum-Vitamin-B12-, Homocystein-, MMA- oder Holo-TC-II-Spiegel unter Metformin-Behandlung festgestellt wurden, sind langfristige prospektive Studien mit hochdosierter Metformin-Behandlung in der pädiatrischen Altersgruppe erforderlich, um unsere Ergebnisse zu bestätigen.

Key words

Metformin - type 2 diabetes mellitus - vitamin B12 - holo-transcobalamin-II - methylmalonic acid

Schlüsselwörter

Metformin - typ 2 diabetes mellitus - vitamin B12 - holo-transcobalamin-II - methylmalonsäure

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