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Does Metformin Cross The Placenta

Diabetes And Pregnancy

Diabetes And Pregnancy

1 . In normal glucose metabolism, where is unused glucose stored following the immediate postprandial period? A) The small intestine B) Muscle and liver tissue C) Fat tissue and pancreas D) Central nervous system Following the immediate postprandial period, unused glucose is stored in muscle and liver tissue as glycogen. The release of this stored energy is regulated by glucagon. Glucagon normally serves as the body's major defense against hypoglycemia. Its role is to maintain blood glucose levels between meals and during the fasting state. When blood glucose levels are high, such as after eating, the secretion of glucagon by the pancreas is inhibited. Click to Review 2 . What is the chief action of the incretin mimetic medications? A) Prolongs active incretin levels B) Increases insulin production from the pancreas C) Decreases insulin production from the pancreas D) Interferes with an enzyme that rapidly inactivates the incretin hormones Many of the more recent therapies developed for the treatment of type 2 diabetes have been incretin-based. One class of medication, the incretin mimetic, mimics the action of the incretin hormones GLP-1 and GIP, leading to an increase in insulin secretion from the pancreas. An additional beneficial effect of these medications is delayed gastric emptying, which increases satiety and promotes weight loss. Click to Review 3 . Which of the following is NOT one of the clinical classes of diabetes defined by the American Diabetes Association? A) Prediabetes B) Type 1 diabetes C) Type 2 diabetes D) Gestational diabetes Diabetes encompasses a relatively large and somewhat diverse group of metabolic diseases. The ADA has identified four different clinical classes of diabetes based upon etiology: type 1, type 2, gestational, and other types. In Continue reading >>

Role Of Insulin In Placental Transport Of Nutrients In Gestational Diabetes Mellitus

Role Of Insulin In Placental Transport Of Nutrients In Gestational Diabetes Mellitus

Abstract Background: Gestational diabetes mellitus (GDM) is associated with increased fetal adiposity, which may increase the risk of obesity in adulthood. The placenta has insulin receptors and maternal insulin can activate its signaling pathways, affecting the transport of nutrients to the fetus. However, the effects of diet or insulin treatment on the placental pathophysiology of GDM are unknown. Summary: There are very few studies on possible defects in the insulin signaling pathway in the GDM placenta. Such defects could influence the placental transport of nutrients to the fetus. In this review we discuss the state of insulin signaling pathways in placentas of women with GDM, as well as the role of exogenous insulin in placental nutrient transport to the fetus, and fetal adiposity. Key Messages: Maternal insulin in the third trimester is correlated with fetal abdominal circumference at that time, suggesting the important role of insulin in this process. Since treatment with insulin at the end of pregnancy may activate placental nutrient transport to the fetus and promote placental fatty acid transfer, it would be interesting to improve maternal hyperlipidemia control in GDM subjects treated with this hormone. More research in this area with high number of subjects is necessary. © 2017 S. Karger AG, Basel Introduction Gestational diabetes mellitus (GDM) is associated with perinatal complications, such as macrosomia in the offspring and increased fetal adiposity, which may increase the risk of obesity, diabetes type 2, and metabolic syndrome in adulthood [1]. Pregnant women diagnosed with gestational diabetes are treated through diet (and exercise) or with insulin in order to avoid hyperglycemia and its adverse effects on fetal development. However, during recent y Continue reading >>

Metformin Therapy And Diabetes In Pregnancy

Metformin Therapy And Diabetes In Pregnancy

Summary No adverse pregnancy outcomes with metformin use have been reported, except in one unmatched study. Otherwise, the studies are small and non-randomised, with the exception of one prospective, randomised controlled trial, currently under way, comparing metformin with insulin in women with gestational diabetes mellitus (the MiG trial). No long-term follow-up data for offspring of mothers receiving metformin have been published. Any woman with diabetes should be as close to euglycaemia as possible before pregnancy. In some circumstances (eg, severe insulin resistance), metformin therapy during pregnancy may be warranted. When metformin treatment is being considered, the individual risks and benefits need to be discussed with the patient so that an appropriate decision can be reached. Continue reading >>

Gestational Diabetes Should You Use Oral Agents?

Gestational Diabetes Should You Use Oral Agents?

Although both glyburide and metformin cross the placental barrier, they appear to be safe to use in treating gestational diabetes. Glyburide and metformin provide effective, convenient, inexpensive alternatives to treatment with insulin. Safety The safety of any drug used in pregnancy depends on whether it crosses the placenta and its effects on the fetus. Many drugs commonly used in pregnancy (eg, magnesium) cross the placenta and exert effects on the fetus, so crossing the placenta alone does not automatically preclude use in pregnancy. Glyburide is a second-generation sulfonylurea that is metabolized by the liver. It works by stimulating the pancreas to produce more insulin. Patients with allergies to sulfa-containing agents should not take this drug. Peak plasma levels of glyburide occur within 4 hours. The US Food and Drug Administration (FDA) categorizes glyburide as a pregnancy Category B drug. Side effects include nausea, vomiting, diarrhea, and pruritic rash. Using a placental cotyledon model of perfusion, Elliott and colleagues demonstrated insignificant transport of glyburide across the placenta.8 Using the same model, Kraemer et al identified active transport of glyburide from the fetal to the maternal circulation, which may help protect the fetus from exposure to the drug.9 Langer et al tested cord blood at delivery and compared it with maternal serum collected simultaneously.10 No neonates had measurable amounts of glyburide in spite of identification of the drug in maternal serum. One study, designed to examine the pharmacokinetics of glyburide in pregnancy, found that cord blood concentrations of glyburide were 70% of maternal serum concentrations.11 Other studies indicate that fetal concentrations of glyburide may be 1% to 2% of maternal concentration.1 Continue reading >>

Metformin Therapy During Pregnancy

Metformin Therapy During Pregnancy

Type 2 diabetes and gestational diabetes mellitus (GDM) are closely related disorders characterized by increased insulin resistance. Metformin, a biguanide compound, exerts its clinical effect by both reducing hepatic glucose output and by increasing insulin sensitivity. This results in a decreased glucose level without an associated high risk of either hypoglycemia or weight gain. These characteristics have established metformin as an ideal first-line treatment for people with type 2 diabetes and, hypothetically, a particularly attractive drug for use in pregnancy. However, metformin is known to cross the placenta (1,2), and its use in pregnancy has been limited by concerns regarding potential adverse effects on both the mother and the fetus. Historically, some of the earliest reports of the use of metformin during pregnancy have come from South Africa, where it has been used since the late 1970s for women with both type 2 diabetes and GDM (3–6). While perinatal mortality for these women was still higher than that seen in the general obstetric population, it was nonetheless lower than in women who had gone untreated and similar to those who were changed to insulin. No “headline” adverse events or side effects were reported. Confidence regarding the use of metformin in pregnancy has been reinforced by the results of several observational studies and randomized trials over the past decade. Two meta-analyses of observational studies—one of women using metformin and/or sulphonylureas and one of women using metformin alone during the first trimester—did not show an increase in congenital malformations or neonatal deaths (7,8). While increased perinatal mortality and pre-eclampsia was noted in one study of 50 women with type 2 diabetes using metformin, these result Continue reading >>

Metformin And Pregnancy: Is It Safe For My Baby?

Metformin And Pregnancy: Is It Safe For My Baby?

Summary: Metformin has gained popularity as another option to treat gestational diabetes. It appears to be safe for baby and mother. However, the human data is still limited and metformin can have potential, and serious, side effects. Also, there is concern that metformin may cross the placental barrier and reach the fetus. Dear Curtis: During my last pregnancy I got gestational diabetes. I’m trying to get pregnant again but obviously my doctor and I are concerned about the possibility of getting the gestational diabetes again. Last time I tried diet and some insulin. But this time I’d like to avoid insulin. My doctor mentioned adding metformin (a diabetes medications). Is this any safer for me and the baby? • Each drug on the market has a pregnancy rating. Metformin is a pregnancy category B. The higher the letter, the safer the drug is. So, metformin, as far as we know, is relatively safe during pregnancy. But there is more to the story. Blood Glucose Levels During Pregnancy First of all, why be so concerned about blood sugars during pregnancy? Well, while it’s not 100% proven just yet, it’s strongly believed that out-of-whack blood sugars during pregnancy can be harmful to the developing baby. Namely, it can lead to birth defects. To try and prevent that doctors do their best to keep blood sugars in check through diet and – when needed – insulin. You’ve already gone the insulin route and – understandably – didn’t care for it. Because of women like yourself doctors have begun using oral diabetes medications like glyburide and metformin. The problem? Despite a pregnancy category B rating for metformin we really don’t have a lot of scientific information on what the long term effects of metformin are on the fetus. I mean, we just don’t design s Continue reading >>

Is It Safe To Use Metformin During Pregnancy?

Is It Safe To Use Metformin During Pregnancy?

Metformin is a commonly used drug for managing type 2 diabetes. It is considered an effective treatment option for many people with diabetes, but is it safe for pregnant women? Metformin is a drug that helps to lower blood sugar. It is considered one of the best first line treatments for type 2 diabetes. A review posted to Diabetology & Metabolic Syndrome notes that metformin helps to lower blood sugar levels, strengthens the endocrine system, improves insulin resistance, and reduces fat distribution in the body. Before taking any drugs, including metformin, a pregnant woman has to be absolutely sure that the drugs will not affect her or her baby. Effects of metformin use during and after pregnancy Some people are concerned about using metformin during and after pregnancy because it crosses the placenta. This means that when a pregnant woman takes metformin, so does her baby. However, the results of the few studies that have been carried out so far into the effects of taking metformin during pregnancy have been positive. A 2014 review posted to Human Reproduction Update found that the drug did not cause birth defects, complications, or diseases. The researchers did note, however, that larger studies should be carried out to make this evidence more conclusive. Metformin and gestational diabetes A separate review posted to Human Reproduction Update noted that women who took metformin to treat gestational diabetes (diabetes during pregnancy) gained less weight than women who took insulin. A 2-year follow-up study found that babies born to the women treated with metformin had less fat around their organs, which could make them less prone to insulin resistance later in life. This could mean that children who are exposed to metformin at a young age could gain long-term benefi Continue reading >>

Impact Of Metformin On Reproductive Tissues: An Overview From Gametogenesis To Gestation

Impact Of Metformin On Reproductive Tissues: An Overview From Gametogenesis To Gestation

Michael J. Bertoldo*, Melanie Faure*, Joelle Dupont, Pascal Froment Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Centre Val de Loire, UMR85, 37380 Nouzilly, France *These authors contributed equally to this work. Correspondence to: Dr. Pascal Froment. Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, 37380 Nouzilly, France. Email: [email protected] Abstract: Metformin is an oral anti-hyperglycemic drug that acts as an insulin sensitizer in the treatment of diabetes mellitus type 2. It has also been widely used in the treatment of polycystic ovary syndrome (PCOS) and gestational diabetes. This drug has been shown to activate a protein kinase called 5' AMP-activated protein kinase or AMPK. AMPK is present in many tissues making metformin’s effect multi factorial. However as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and fetus. The majority of reports suggest no significant adverse effects or teratogenicity. However, disconcerting reports of male mouse offspring that were exposed to metformin in utero that present with a reduction in testis size, seminiferous tubule size and in Sertoli cell number suggest that we do not understand the full suite of effects of metformin. In addition, recent molecular evidence is suggesting an epigenetic effect of metformin which could explain some of the long-term effects reported. Nevertheless, the data are still insufficient to completely confirm or disprove negative effects of metformin. The aims of this review are to provide a summary of the safety of metformin in various aspects of sexual reproduction, the use of metform Continue reading >>

Metformin In Women With Type 2 Diabetes In Pregnancy (mity): A Multi-center Randomized Controlled Trial

Metformin In Women With Type 2 Diabetes In Pregnancy (mity): A Multi-center Randomized Controlled Trial

Abstract The incidence of type 2 diabetes in pregnancy is rising and rates of serious adverse maternal and fetal outcomes remain high. Metformin is a biguanide that is used as first-line treatment for non-pregnant patients with type 2 diabetes. We hypothesize that metformin use in pregnancy, as an adjunct to insulin, will decrease adverse outcomes by reducing maternal hyperglycemia, maternal insulin doses, maternal weight gain and gestational hypertension/pre-eclampsia. In addition, since metformin crosses the placenta, metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes. Our aim is to compare the effectiveness of the addition of metformin to insulin, to standard care (insulin plus placebo) in women with type 2 diabetes in pregnancy. The MiTy trial is a multi-centre randomized trial currently enrolling pregnant women with type 2 diabetes, who are on insulin, between the ages of 18–45, with a gestational age of 6 weeks 0 days to 22 weeks 6 days. In this randomized, double-masked, parallel placebo-controlled trial, after giving informed consent, women are randomized to receive either metformin 1,000 mg twice daily or placebo twice daily. A web-based block randomization system is used to assign women to metformin or placebo in a 1:1 ratio, stratified for site and body mass index. The primary outcome is a composite neonatal outcome of pregnancy loss, preterm birth, birth injury, moderate/severe respiratory distress, neonatal hypoglycemia, or neonatal intensive care unit admission longer than 24 h. Secondary outcomes are large for gestational age, cord blood gas pH < 7.0, congenital anomalies, hyperbilirubinemia, sepsis, hyperinsulinemia, shoulder dystocia, fetal fat mass, as well as maternal outcomes: maternal weight gain, maternal in Continue reading >>

Polycystic Ovary Syndrome — Unique Concerns During Pregnancy And Lactation

Polycystic Ovary Syndrome — Unique Concerns During Pregnancy And Lactation

Today’s Dietitian Vol. 10 No. 12 P. 38 For many women with PCOS, conceiving is only the first hurdle. These women face particular challenges, but RDs can help them achieve healthy pregnancies by addressing their special emotional, health, and dietary needs. Polycystic ovary syndrome (PCOS) is identified as a state of hyperinsulinemia and hyperandrogenism. Affecting 8% to 10% of reproductive-age women, it is the main cause of ovulatory infertility in the United States.1 Pregnancy can be an exciting time for women with PCOS, especially because so many of them may have been trying to conceive for years, with or without fertility treatments. In addition, being pregnant is a sign of femininity, and it may be a relief to some women who have felt masculine due to their “male” shape and symptoms such as excess hair growth and balding. However, having PCOS and being pregnant does pose some concerns. Some women who have undergone fertility treatments may carry multiple babies and will have special dietary and medical needs. Also, because many women with PCOS have hormonal imbalances and are overweight or obese, they are at higher risk for miscarriage and complications such as gestational diabetes mellitus and hypertensive disorders during pregnancy.2-6 Proper medical management and medical nutrition therapy are imperative to prevent the onset of these complications and optimize fetal growth and development. Emotional Concerns Many women with PCOS who are able to conceive may have misconceptions about eating healthfully during pregnancy. Popular diet guidelines for PCOS (mostly from the Internet) recommend a very low-carbohydrate diet, but current evidence does not support it. Women who follow these recommendations may feel apprehensive about eating foods containing carbohyd Continue reading >>

Metformin In Gestational Diabetes: An Emerging Contender

Metformin In Gestational Diabetes: An Emerging Contender

1 Consultant Endocrinologist, Department of Endocrinology, G. D Hospital and Diabetes Institute, Kolkata, West Bengal ; Chief Endocrinologist, Department of Endocrinology, Sun Valley Diabetes Hospital, Guwahati, Assam, India 2 Consultant Gynecologist, Department of Gynecology, G. D Hospital and Diabetes Institute, Kolkata, West Bengal, India Correspondence Address: Awadhesh Kumar Singh Flat 1C, 3 Canal Street, Kolkata, West Bengal - 700 014 India Source of Support: None, Conflict of Interest: None DOI: 10.4103/2230-8210.149317 Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance occurring first time during pregnancy. Its prevalence is simultaneously increasing with the global rise of diabesity. GDM commonly develops, when maternal glucose metabolism is unable to compensate for the progressive development of insulin resistance, arising primarily from the consistently rising diabetogenic placental hormones. It classically develops during the second or third trimester. Theoretically, insulin sensitizers should have been the ideal agent in its treatment, given the insulin resistance, the major culprit in its pathogenesis. Fortunately, majority of women can be treated satisfactorily with lifestyle modification, and approximately 20% requires more intensive treatment. For several decades, insulin has been the most reliable treatment strategy and the gold standard in GDM. Metformin is effective insulin sensitizing agent and an established first line drug in type 2 diabetes currently. As it crosses the placenta, a safety issue remains an obstacle and, therefore, metformin is currently not recommended in the treatment of GDM. Nevertheless, given the emerging clinically equivalent safety and efficacy data of metformin compared to insulin, it appears Continue reading >>

Evidence Shows Possible Benefit Of Metformin And Glyburide Use In Pregnancy

Evidence Shows Possible Benefit Of Metformin And Glyburide Use In Pregnancy

A review of recent studies suggests that some oral hypoglycemic agents may be safe and effective in pregnant patients…. Insulin is traditionally the treatment of choice in pregnant patients requiring medication to manage their blood glucose levels, as it is a hormone the body already produces naturally and should therefore theoretically pose less risk to a developing fetus. New evidence, however, suggests that certain oral hypoglycemic agents may be suitable alternatives for these patients. These oral agents would help to simplify medication regimens in many of these patients, as insulin administration is known to be demanding, unpleasant, and inconvenient. A literature search was performed using Pubmed and other electronic databases to identify articles pertaining to this topic. In particular, the keywords pregnancy, diabetes, and the names of different oral hypoglycemic agents were used to find this information. Manufacturers of different oral agents were also contacted for further information. Studies found metformin to be safe for use throughout pregnancy, and to be associated with several additional benefits. These include: reduced pregnancy loss, less maternal weight gain, and less neonatal hypoglycemia. Also, several studies found an up to 10-fold reduction in incident gestational diabetes in women treated with metformin. A trial is currently being conducted to examine whether it is beneficial to begin metformin therapy in pregnant type 2 diabetics treated with insulin, as previous studies focus on type 1. Randomized controlled trials in patients with gestational diabetes found no difference in a composite of neonatal complications between patients taking metformin and patients using insulin. Metformin was also found to have a higher treatment satisfaction rate Continue reading >>

Metformin Use In Pregnancy: Promises And Uncertainties

Metformin Use In Pregnancy: Promises And Uncertainties

Go to: Early use The initial development and use of metformin (outside of pregnancy) are reviewed elsewhere in this issue of Diabetologia [1]. With regard to pregnancy, it is important to note that it was acknowledged very early on that metformin crossed the placenta. More recent studies show similar plasma concentrations in the maternal and fetal circulation [2]. Further, the combination of increased lactic acidosis risk (mainly observed with the metformin-related biguanide, phenformin) and the relatively hypoxic fetal environment led to important concerns regarding potential adverse effects of metformin use in pregnancy, for both mother and child. In fact, the safety concerns related to phenformin use resulted in the withdrawal of metformin in many, although not all, countries [3]. These early concerns are charted in influential reports of the Aberdeen International Colloquia on Carbohydrate Metabolism in Pregnancy and the Newborn. The first colloquium, reported in 1975, included an entire chapter on ‘the use of sulphonylureas, biguanides and insulin in pregnancy’ [4]. By the time of the fourth report in 1988, the topic of use of metformin was given only a few lines and it was noted that use was not widespread [5]. Metformin use did, however, continue in other parts of the world. In developing countries, the relatively low cost of metformin compared with insulin made it an attractive option. Coetzee and colleagues published a series of important observational papers, commencing in the late 1970s, examining the use of metformin in South Africa [6–8]. In South Africa and other countries, where metformin was routinely used to treat type 2 diabetes, exposure inevitably began to occur in early pregnancy leading to the separate analysis of safety in early pregnancy, p Continue reading >>

Glyburide As Effective As Insulin For Gestational Diabetes [classics Series]

Glyburide As Effective As Insulin For Gestational Diabetes [classics Series]

1. Among women with gestational diabetes requiring treatment, those randomized to glyburide achieved similar glycemic control to women in the insulin control group. Original Date of Publication: October 2000 Study Rundown: The adverse pregnancy outcomes associated with diabetes have been well documented. Following diagnosis, women with gestational diabetes mellitus are initially managed with dietary therapy, termed modified nutritional therapy (MNT). If glycemic control is not achieved with MNT, the next step in treatment is the initiation of insulin therapy. Insulin is well-studied in pregnancy and known to be highly effective and safe. Yet, insulin is an expensive and onerous treatment that can be cumbersome to learn, inconvenient and difficult to adhere to, and painful for patients. Oral agents are a well-established treatment for insulin-dependent diabetes outside of pregnancy. They have been infrequently used in pregnancy, however, due to demonstrated risks of neonatal hypoglycemia associated with early-generation sulfonylurea drugs and metformin, both of which cross the placenta. Sulfonylurea drugs improve glycemic control by increasing insulin secretion, which decreases hepatic glucose production and thereby indirectly improves insulin sensitivity. Subsequent to these investigations, however, newer oral hypoglycemic agents were developed, including glyburide. Study authors of the present work investigated the pharmacologic profile of glyburide in pregnant women and found that glyburide does not cross the human placenta in any meaningful concentration. Given this low likelihood that glyburide crosses the placenta and the mild degree of hyperglycemia affecting most women with gestational diabetes, authors postulated that treatment with glyburide might achieve glyce Continue reading >>

2017 Ada Guidelines: Diabetes During Pregnancy

2017 Ada Guidelines: Diabetes During Pregnancy

Below you can find ADA standards on proper A1c targets, blood pressure range, retinopathy monitoring and medications used in preexisting and gestational diabetes. The preferred medications during pregnancy are insulin, metformin and glyburide. Recommendations are listed below with slightly modified wording for easier and succinct reading: GT Diabetes Care ADA Guidelines January 2017 Preexisting Diabetes Preconception counseling should address the importance of glycemic control as close to normal as is safely possible, ideally A1C <6.5% to reduce the risk of congenital anomalies. Women with preexisting type 1 or type 2 diabetes who are planning pregnancy or who have become pregnant should be counseled on the risk of development and/or progression of diabetic retinopathy. Dilated eye examinations should occur before pregnancy or in the first trimester, and then patients should be monitored every trimester and for 1 year postpartum as indicated by degree of retinopathy and as recommended by the eye care provider. Gestational Diabetes Mellitus Lifestyle change is an essential component of management of gestational diabetes mellitus and may suffice for the treatment for many women. Medications should be added if needed to achieve glycemic targets. Insulin is the preferred medication for treating hyperglycemia in gestational diabetes mellitus, as it does not cross the placenta to a measurable extent. Metformin and glyburide may be used, but both cross the placenta to the fetus, with metformin likely crossing to a greater extent than glyburide. All oral agents lack long-term safety data. Metformin, when used to treat polycystic ovary syndrome and induce ovulation, need not be continued once pregnancy has been confirmed. General Principles Potentially teratogenic medications (A Continue reading >>

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