Owen, MD, Baker, BC, Scott, EM et al. (1 more author) (Cover date: 01 June 2021) Interaction Between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies. International Journal of Molecular Sciences, 22 (11). 5759. ISSN 1661-6596
Abstract
Metformin is the first line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentra-tions of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of ‘catch up’ growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on fetal growth and long-term health of the offspring remain to be established. Metformin is associated with ma-ternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate: vitamin B12 imbalance induced by metformin may lead to genomic instabil-ity and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic res-piration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin sup-plementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogenous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate: vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin thus it is of paramount importance to improve our understanding of metformin’s transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). |
Keywords: | metformin; diabetes; placenta; folate; vitamin B12; one carbon metabolism; fetal growth; LGA; SGA; fetal programming |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/R023166/1 British Heart Foundation FS/4yPhD/F/20/34130 |
Depositing User: | Symplectic Publications |
Date Deposited: | 27 May 2021 14:39 |
Last Modified: | 14 Sep 2023 10:46 |
Published Version: | https://www.mdpi.com/1422-0067/22/11/5759 |
Status: | Published |
Publisher: | MDPI |
Identification Number: | 10.3390/ijms22115759 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:174540 |