AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2642-9756/094
1 General Physician, Universidad Técnica de Ambato, Ecuador
2 General Physician, Universidad Militar Nueva Granada, Bogotá, Colombia
3 General Physician, Universidad del Sinú de Montería, Colombia
4General Physician, Universidad del Sinú, Colombia
5 General Physician, Universidad Industrial de Santander, Colombia
6 General Physician, Universidad del Sinú, Colombia
7 General Physician, Universidad del Sinú, Cartagena, Colombia
8 General Physician, Universidad del Norte, Colombia
*Corresponding Author: Karen Mireya Topa Pila, General Physician, Universidad Técnica de Ambato, Ecuador.
Citation: Topa Pila KM, Carlos A. Reyes., Llanos Guzmán MA., Zetién Arteaga HR., Gómez Flórez LY, et all (2021). Perinatal Effects of Metformin use in Gestational Diabetes. J. Women Health Care and Issues. 4(7); DOI:10.31579/2642-9756/094
Copyright: © 2021 Karen Mireya Topa Pila, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 18 November 2021 | Accepted: 03 December 2021 | Published: 08 December 2021
Keywords: metformin; macrosomia; gestational diabetes
Background: GD is a condition in which a woman develops glucose intolerance at any time during pregnancy and may or may not resolve at the end of pregnancy. Metformin, from the group of biguanides, is considered an alternative management of gestational diabetes, included in the list of essential medicines by the OMS.
Methodology: A narrative review was carried out through various databases from March 2018 to September 2021; the search and selection of articles was carried out in journals indexed in English and Spanish. The following keywords were used: metformin, macrosomia, gestational diabetes.
Results: The present review offers pathophysiological measures, complications, pharmacological therapy, for a better approach in perinatals in patients with gestational diabetes.
Conclusion: With the results observed, it should be noted that metformin is viable for the management of patients with gestational diabetes.
Gestational diabetes is a decrease in tolerance to carbohydrates that occurs during pregnancy, is associated with adverse results for both the mother and the fetus if it is not controlled, it usually occurs in the second trimester of pregnancy, Since in this they develop an increase in peripheral resistance to insulin at the post-receptor level mediated by high plasma levels of diabetogenic hormones, however, it reaches its peak at week 32, this would have risky maternal-fetal consequences. (1)
When normal glucose figures are not obtained with treatment based on diet and exercise, it is necessary to implement pharmacological treatment, with oral hypoglycemic agents, taking into account that metabolic control is essential to avoid perinatal complications for the mother, such as hypertension gestational disease, pre-eclampsia, development of postpartum type II DM, polyhydramnios and premature delivery, among others. In the case of the fetus, complications such as macrosomia, hypoglycemia, hyperbilirubinemia, hypocalcemia, among other complications, can be generated. It should be noted that several studies affirm that the use of metformin for glycemic control is safe and effective, especially for lower strata, since thanks to its low commercial cost it is accessible and there is better adherence to its route of administration, although its Long-term effects. [1,2]
Treatment methods may vary depending on the characteristics of each patient, including insulin and metformin being the most favorable options for the treatment of gestational diabetes.
The objective of this article is to identify the possible perinatal effects that may occur due to the consumption of metformin in gestational diabetes.
A narrative review was carried out, in which the databases of the Journal of Medical-Surgical Specialties, Elsevier, and ScienceDirect, among others, were searched. The collection and selection of articles was carried out in journals indexed in English from the years 2018 to 2021. As keywords, the terms were used in the databases according to the DeCS and MeSH methodology; metformin, macrosomia, diabetes. In this review, 716 original and review publications related to the subject studied were identified, of which 15 articles met the specified inclusion requirements, such as articles that were in a range not less than the year 2018, which were articles of full text and to report on the perinatal effects of the use of metformin in gestational diabetes. As exclusion criteria, it was taken into account that the articles did not have sufficient information and that they did not present the full text at the time of their review.
Pathophysiology of gestational diabetes
It should be noted that for the approach to this pathology it is important to remember that during the first 6 of normal pregnancy, estrogens and progesterone stimulate hyperplasia of the B cells of the pancreas in addition to generating increases in insulin secretion in order to increase the glycogen stores for subsequent fetal growth. During this stage, insulin resistance remains stable; As gestation progresses, insulin sensitivity decreases to 50% in the third trimester. During this process, the production of placental lactogen and growth hormones participates, releasing cytokines by adipocytes, which increases the concentration of free acids, in addition to a decrease in the plasma concentration of adiponectin, All of the above results in a peripheral decrease in glucose between 40 and 60%. [2]
Because glucose is transported to the fetus by means of facilitated diffusion, physiological insulin resistance favors the uptake of fetal glucose in such a way that in a normal pregnancy, glycemia remains within normal ranges by an increase between 200-250% insulin. [2.1]
Following the topic, the regulation of fetal glucose metabolism requires that the maternal glucose concentration, the placental transfer of glucose and the adequate production of fetal insulin be established to be stable, in addition to its entry into peripheral fetal tissues. [2.2]
Women diagnosed with gestational diabetes show an increase in fasting and postprandial glucose, which generates greater fetal glucose transfer and stimulates fetal insulin secretion, during the state of fetal hyperinsulinemia promotes anabolism which causes large fetuses for gestational age and increased risk of organic damage. [23]
Complications of gestational diabetes.
As we well know, gestational diabetes does not present symptoms, for this reason it is important to carry out an early diagnosis in a timely manner, since if it is not treated in time, it presents maternal-fetal complications. [3]
Among the maternal risks that have been documented are; increased risk of hypertensive diseases which is related to fluctuations in glucose levels since these have a greater impact on the endothelial function of sustained hyperglycemia, in these patients there is a greater need for induction of labor and cesarean section In addition to the fact that there is a greater risk of uterine rupture, shoulder dystocia, and perinatal relationships due to the presence of large-for-gestational age neonates, it has also been documented that there is a greater risk of preterm delivery and the presence of metabolic dysfunction with a cumulative incidence of DM2 that it ranges from 10 to 20% within the next 10 years. [3.1]
Now, speaking of the children of mothers with gestational diabetes, adverse neonatal complications include growth disorders (macrosomia), neonatal hypoglycemia, respiratory distress syndrome, perinatal asphyxia, fractures, brachial plexus palsy, neonatal hyperbilirubinemia, hypertrophic heart disease, polycythemia, hypocalcemia, hypomagnesemia, and higher rate of admission to the neonatal intensive care unit (NICU), there is evidence that fetal hyperinsulinemia produces hypokalemia, which can cause fetal arrhythmias and ultimately death (Figure 1). [4]
Taken from Cozma MA, Găman MA, Dobrică EC, Boroghină SC, Iancu MA, Crețoiu SM, Simionescu AA. A look at the size of the fetal liver: is it related to the course of gestational diabetes? International Journal of Molecular Sciences. 2021; 22 (15): 7866. https://doi.org/10.3390/ijms22157866
Preterm birth is the leading cause of neonatal death in pregnant diabetics. Fetal hyperglycemia and hyperinsulinemia interfere with surfactant synthesis by type 2 pneumocytes and lung maturation, conferring an increased risk of respiratory distress and neonatal death. [5]
It is important to highlight that intrauterine conditions in which tissues and organs develop have greater adiposity, fatty tissue and more skin folds, in addition to the increased risk of presenting long-term metabolic complications such as being overweight among others. [6]
Metformin
Metformin, belonging to the group of biguanides, is the first choice in patients with diabetes, with preserved renal function after recommending initiating a change in lifestyle at the time of GD diagnosis, as agreed by the European Association for the Study of Diabetes (EASD), the American Diabetes Association (ADA) and the main clinical practice guidelines. Even when these patients initiate insulinization, metformin treatment should continue.
Pharmacological treatment is favored by its low cost, easy administration, and acceptability among patients, making it an acceptable alternative. Highlighting that, being a hypoglycemic agent, metformin is considered a potential substitute for insulin in the management of gestational diabetes. In controlled studies involving women with GD, the use of metformin, either in conjunction with insulin or alone, was not associated with an increase in perinatal complications compared to insulin alone. Metformin began to be used to treat diabetes in humans in 1995, which was approved for use in the United States, while its first report in pregnant women was registered in 1970. [7]
Among the effects of metformin is the suppression of hepatic gluconeogenesis, which could be beneficial for the preservation of the function of pancreatic B cells, which increases the suppression of insulin, stimulates the uptake of glucose in peripheral tissue and reduction of glucose absorption in the gastrointestinal tract, thus increasing insulin sensitivity without stimulating its release in such a way that it does not generate hypoglycemia (Figure 2). [8]
Taken from Priya, G., & Kalra, S. (2018). Metformin in the management of diabetes during pregnancy and lactation. Drugs in context, 7, 212523. https://doi.org/10.7573/dic.212523
Metformin is incompletely absorbed in the intestinal mucosa, it shows stable concentrations in plasta within the first 24 and 48 hours after its ingestion, its use is contraindicated in patients with renal failure. [9]
Perinatal effects of metformin
Metformin is well tolerated in most patients, although it does cause gastrointestinal adverse effects such as abdominal discomfort, loose stools, and diarrhea. In general, these side effects appear shortly after the start of metformin treatment and disappear quickly after stopping it. Metformin is not associated with hypoglycemia or weight gain and reduces the risk of complications and mortality
As far as we are concerned, the use of metformin in patients with the diagnosis of GD is considered a safe management since no serious complications have been reported with its use, neither maternal, nor fetal, nor newborn, with a rate high efficiency of 53.7% when it was used as the only drug. The amount of insulin required for metabolic control (in patients where it was required) is less than when using insulin alone, and the mother is less likely to suffer from hypoglycemia. Maternal weight gain is lower with the use of metformin compared to those using insulin alone or glyburide for the management of gestational diabetes. [10]
No studies were found where differences will be observed between patients and their children when they used metformin. Long-term follow-up of newborns is important to assess in the future to verify that everything is going well in the motor and social development of the children. [11]
Published studies on the perinatal effects of metformin in women with gestational diabetes show that metformin improves glucose tolerance and reduces the accumulation of body weight and fat mass in the offspring in adulthood. A comparative study (metformin vs placebo) (n = 849 patients) reported that obstetrically metformin was associated with a lower maternal weight gain (p 0.0002), the literature refers unsatisfactory results in the investigation of lifestyle changes and diet to reduce the weight gain in pregnant women with obesity, however in this study, the change in lifestyle and adherence to pharmacological treatment was positively evidenced by the weight gain found in the women included in this study and it is reported at an estimated 7.9 kg during gestation. [12]
The data collected during their research in the study carried out by DR Álvaro Joffre luna et al, demonstrate that pharmacological management with metformin and the advantage of lower weight gain during pregnancy shows a lower incidence of low weight for age In addition to exposing the advantages of the consumption of this drug with respect to the increase in maternal weight and the weight of the newborn, as we well know the risk of suffering from hypertensive diseases during pregnancy due to gestational diabetes is due to fluctuations in the levels of glucose, which generates a greater part in endothelial function, compared to sustained hyperglycemia, for which comparative analyzes have been carried out in which a slight increase in the incidence of hypertensive diseases of pregnancy was reported in the group that were managed with metformin compared to other drugs such as insulin without statistically significant differences. [13]
It should be noted that there is evidence showing that metformin reduces the risk of hypertensive diseases of pregnancy and is associated with a lower percentage of pre-eclampsia. [13.1]
Different studies have shown that the majority (93.8%) of pregnant women achieve glycemic control using metformin therapy, with a low rate of failures and side effects (4.6%) [13,2]
The MIGTOFU, whose objective the study gestational diabetes treated with insulin vs metformin, demonstrated lower rates of severe hypoglycemia (3.3% vs 8.1, p = 0.008) in those treated with metformin and maternal glycemia during pregnancy was similar in the two subgroups. [14]
Thanks to all the research found, it can be concluded that there is a good relationship between the use of metformin and obstetric and perinatal findings in high-risk pregnant patients with gestational diabetes, because it is low-cost and is available to all in any stratum and that the route of administration contributes to adherence to treatment by patients. (fifteen)
A strength of the current study is the methodology implemented, with respect to the literature search, and steps in the selection of relevant articles, quality assessment and data extraction. However, this study has several limitations, which should be taken into account before reaching a conclusion, within these are the little evidence from clinical studies that show that metformin generates any adverse effect on pregnancy or the fetus.
It can be emphasized that during the research carried out it was concluded taking into account the collection of data from various sources, where it has been shown that the use of metformin in pregnant women diagnosed with gestational diabetes, treated with this drug, does not exist to date or The causes and / or adverse effects that complicate or endanger both the fetus and the mother are unknown, as well as complications during the gestation period, since according to the results obtained in the research, a high percentage was found, around a 70%, where the patients report efficacy of the drug and a small percentage of side effects, the fetuses were also followed during the gestation period, they did not present any anatomical or cognitive abnormality after delivery, but it is suggested to follow up to babies exposed to metformin later on.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
