Metformin is being studied in two ongoing trials in type 2 diabetes (Metformin in Women with Type 2 Diabetes in Pregnancy Trial [MiTY] [76] and Medical Optimization of Management of Type 2 Diabetes Complicating Pregnancy [MOMPOD] [77]), but long-term offspring data will not be available for some time. More studies are needed to assess the long-term effects of prenatal aspirin exposure on offspring (113). Diabetes Care also publishes the ADAs recommendations and statements, clinically relevant review articles, editorials and commentaries. A. 3/6/18, 3/12/2019, 3/9/2021. More than 122 million Americans have diabetes or prediabetes and are striving to manage their lives while living with the disease. Long-term safety data for offspring exposed to glyburide are not available (66). Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. Observational studies show an increased risk of diabetic embryopathy, especially anencephaly, microcephaly, congenital heart disease, renal anomalies, and caudal regression, directly proportional to elevations in A1C during the first 10 weeks of pregnancy (3). In one study, insulin requirements in the immediate postpartum period are roughly 34% lower than prepregnancy insulin requirements (113,114). Prescription of prenatal vitamins (with at least 400 g of folic acid and 150 g of potassium iodide [17]) is recommended prior to conception. Oral agents may be an alternative in these women after a discussion of the known risks and the need for more long-term safety data in offspring. Metformin and glyburide should not be used as first-line agents, as both cross the placenta to the fetus. A recent Cochrane systematic review was not able to recommend any specific insulin regimen over another for the treatment of diabetes in pregnancy (90). Available from, Aspirin for the prevention of preterm and term preeclampsia: systematic review and metaanalysis, Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia, Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial, A Cost-benefit analysis of low-dose aspirin prophylaxis for the prevention of preeclampsia in the United States, Aspirin for the prevention of preeclampsia and potential consequences for fetal brain development, International Society for the Study of Hypertension in Pregnancy (ISSHP), Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice, ACOG Practice Bulletin No. Glyburide was associated with a higher rate of neonatal hypoglycemia, macrosomia, and increased neonatal abdominal circumference than insulin or metformin in meta-analyses and systematic reviews (72,73). 2. Classification and Diagnosis of Diabetes: Standards of - PubMed Appropriate use of over-the-counter medications and supplements, Evaluation of diabetes and its comorbidities and complications, including: DKA/severe hyperglycemia; severe hypoglycemia/hypoglycemia unawareness; barriers to care; comorbidities such as hyperlipidemia, hypertension, NAFLD, PCOS, and thyroid dysfunction; complications such as macrovascular disease, nephropathy, neuropathy (including autonomic bowel and bladder dysfunction), and retinopathy, Evaluation of obstetric/gynecologic history, including history of: cesarean section, congenital malformations or fetal loss, current methods of contraception, hypertensive disorders of pregnancy, postpartum hemorrhage, preterm delivery, previous macrosomia, Rh incompatibility, and thrombotic events (DVT/PE), Review of current medications and appropriateness during pregnancy, Diabetes complications and comorbidities, including: comprehensive foot exam; comprehensive ophthalmologic exam; ECG in women starting at age 35 years who have cardiac signs/symptoms or risk factors, and if abnormal, further evaluation; lipid panel; serum creatinine; TSH; and urine protein-to-creatinine ratio. A referral for a comprehensive eye exam is recommended. However, due to the potential for growth restriction or acidosis in the setting of placental insufficiency, metformin should not be used in women with hypertension or preeclampsia or at risk for intrauterine growth restriction (88,89). Insulin sensitivity then returns to prepregnancy levels over the following 12 weeks. Insulin resistance drops rapidly with delivery of the placenta. Offspring with exposure to untreated GDM have reduced insulin sensitivity and -cell compensation and are more likely to have impaired glucose tolerance in childhood (51). A, 15.26 Women with a history of gestational diabetes mellitus should have lifelong screening for the development of type 2 diabetes or prediabetes every 13 years. American Diabetes Association. American Diabetes Association; 14. (Evidence A)Long-term use of Metformin may be associated with biochemical vitamin B12 . A large study found that after adjusting for confounders, first trimester ACE inhibitor exposure does not appear to be associated with congenital malformations (20). Table 3. There are opportunities to educate all women and adolescents of reproductive age with diabetes about the risks of unplanned pregnancies and about improved maternal and fetal outcomes with pregnancy planning (9). The Diabetes in Early Pregnancy Study, A focused preconceptional and early pregnancy program in women with type 1 diabetes reduces perinatal mortality and malformation rates to general population levels, Effectiveness of a regional prepregnancy care program in women with type 1 and type 2 diabetes: benefits beyond glycemic control, Cost-benefit analysis of preconception care for women with established diabetes mellitus, ATLANTIC DIP: closing the loop: a change in clinical practice can improve outcomes for women with pregestational diabetes, Implementation of guidelines for multidisciplinary team management of pregnancy in women with pre-existing diabetes or cardiac conditions: results from a UK national survey, Insulin requirements throughout pregnancy in women with type 1 diabetes mellitus: three changes of direction, The association of falling insulin requirements with maternal biomarkers and placental dysfunction: a prospective study of women with preexisting diabetes in pregnancy, Preprandial versus postprandial blood glucose monitoring in type 1 diabetic pregnancy: a randomized controlled clinical trial, Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy, National Institute of Child Health and Human DevelopmentDiabetes in Early Pregnancy Study, Maternal postprandial glucose levels and infant birth weight: the Diabetes in Early Pregnancy Study, Committee on Practice BulletinsObstetrics, ACOG Practice Bulletin No. During pregnancy, treatment with ACE inhibitors and angiotensin receptor blockers is contraindicated because they may cause fetal renal dysplasia, oligohydramnios, pulmonary hypoplasia, and intrauterine growth restriction (20). Glyburide failed to be found noninferior to insulin based on a composite outcome of neonatal hypoglycemia, macrosomia, and hyperbilirubinemia (74). Target range 63140 mg/dL (3.57.8 mmol/L): TIR, goal >70%, Time below range (<63 mg/dL [3.5 mmol/L]), goal <4%, Time below range (<54 mg/dL [3.0 mmol/L]), goal <1%. Two designated representatives of the American College of Cardiology (ACC) reviewed and provided feedback on the "Cardiovascular Disease and Risk Management" section, and this section received endorsement from ACC. It can also include daily blood glucose testing and insulin injections. After diagnosis, treatment starts with medical nutrition therapy, physical activity, and weight management, depending on pregestational weight, as outlined in the section below on preexisting type 2 diabetes, as well as glucose monitoring aiming for the targets recommended by the Fifth International Workshop-Conference on Gestational Diabetes Mellitus (54): Fasting glucose <95 mg/dL (5.3 mmol/L) and either, One-hour postprandial glucose <140 mg/dL (7.8 mmol/L) or, Two-hour postprandial glucose <120 mg/dL (6.7 mmol/L). Breastfeeding may also confer longer-term metabolic benefits to both mother (116) and offspring (117). Taking all of this into account, a target of <6% (42 mmol/mol) is optimal during pregnancy if it can be achieved without significant hypoglycemia. A follow-up study at 510 years showed that the offspring had higher BMI, weight-to-height ratios, waist circumferences, and a borderline increase in fat mass (82,83). Here's what these new updates mean, including your options for first-line glucose-lowering therapies, when you should be screened for diabetes, the expanded use of diabetes care technology, and more. E, 15.6 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. C. Pregnancy in women with normal glucose metabolism is characterized by fasting levels of blood glucose that are lower than in the nonpregnant state, due to insulin-independent glucose uptake by the fetus and placenta, and by mild postprandial hyperglycemia and carbohydrate intolerance as a result of diabetogenic placental hormones. Planning pregnancy is critical in women with preexisting diabetes due to the need for preconception glycemic control to prevent congenital malformations and reduce the risk of other complications. E, 14.20 Potentially harmful medications in pregnancy (i.e., ACE inhibitors, angiotensin receptor blockers, statins) should be stopped at conception and avoided in sexually active women of childbearing age who are not using reliable contraception. C, 14.22 A contraceptive plan should be discussed and implemented with all women with diabetes of reproductive potential. The OGTT is recommended over A1C at 412 weeks postpartum because A1C may be persistently impacted (lowered) by the increased red blood cell turnover related to pregnancy, by blood loss at delivery, or by the preceding 3-month glucose profile. In general, specific risks of diabetes in pregnancy include spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia, hyperbilirubinemia, and neonatal respiratory distress syndrome, among others. The 2021 Standards of Care is now live online in Diabetes Care. This was not found in the Adelaide cohort. In the second and third trimesters, A1C <6% (42 mmol/mol) has the lowest risk of large-for-gestational-age infants (39,42,43), preterm delivery (44), and preeclampsia (1,45). E. Because GDM often represents previously undiagnosed prediabetes, type 2 diabetes, maturity-onset diabetes of the young, or even developing type 1 diabetes, women with GDM should be tested for persistent diabetes or prediabetes at 412 weeks postpartum with a 75-g OGTT using nonpregnancy criteria as outlined in Section 2 Classification and Diagnosis of Diabetes (https://doi.org/10.2337/dc21-S002). Around 16 weeks, insulin resistance begins to increase, and total daily insulin doses increase linearly 5% per week through week 36. 14.16 Insulin should be used for management of type 1 diabetes in pregnancy. B, 14.5 In addition to focused attention on achieving glycemic targets A, standard preconception care should be augmented with extra focus on nutrition, diabetes education, and screening for diabetes comorbidities and complications. The OGTT is more sensitive at detecting glucose intolerance, including both prediabetes and diabetes. The pharmacologic basis for better clinical practice, Pharmacokinetics, efficacy and safety of glyburide for treatment of gestational diabetes mellitus, Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis, Groupe de Recherche en Obsttrique et Gyncologie (GROG), Effect of glyburide vs subcutaneous insulin on perinatal complications among women with gestational diabetes: a randomized clinical trial, Metformin compared with glyburide for the management of gestational diabetes, Glyburide versus metformin and their combination for the treatment of gestational diabetes mellitus: a randomized controlled study, Comparative efficacy and safety of OADs in management of GDM: network meta-analysis of randomized controlled trials, Placental passage of metformin in women with polycystic ovary syndrome, Population pharmacokinetics of metformin in late pregnancy, Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7-9 years of age, Metformin use in PCOS pregnancies increases the risk of offspring overweight at 4 years of age: follow-up of two RCTs, Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: a systematic review and meta-analysis, Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5-10 year follow-up of the PregMet randomised controlled trial. However, ACE inhibitors and angiotensin receptor blockers should be stopped as soon as possible in the first trimester to avoid second and third trimester fetopathy (21). A systematic review and meta-analysis of observational studies of preconception care for women with preexisting diabetes demonstrated lower A1C and reduced risk of birth defects, preterm delivery, perinatal mortality, small-for-gestational-age births, and neonatal intensive care unit admission (8). Diabetes Care, a monthly journal of the American Diabetes Association (ADA), is the highest-ranked, peer-reviewed journal in the field of diabetes treatment and prevention. In these women, lifestyle intervention and metformin reduced progression to diabetes by 35% and 40%, respectively, over 10 years compared with placebo (124). Postprandial monitoring is associated with better glycemic control and a lower risk of preeclampsia (3234). 15.19 Women with type 1 or type 2 diabetes should be prescribed low-dose aspirin 100150 mg/day starting at 12 to 16 weeks of gestation to lower the risk of preeclampsia. Women with diabetes have the same contraception options and recommendations as those without diabetes. The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Selection of CGM device should be individualized based on patient circumstances. In general, specific risks of diabetes in pregnancy include spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia, hyperbilirubinemia, and neonatal respiratory distress syndrome, among others. This Guideline was approved November 13, 2016, and updated February 12, 2018. Diabetes Care 2021;44(Suppl. Preconception counseling resources tailored for adolescents are available at no cost through the American Diabetes Association (ADA) (15). Preprandial testing is also recommended when using insulin pumps or basal-bolus therapy so that premeal rapid-acting insulin dosage can be adjusted. Dilated eye examinations should occur ideally before pregnancy or in the first trimester, and then patients should be monitored every trimester and for 1 year postpartum as indicated by the degree of retinopathy and as recommended by the eye care provider. Your donation is free, convenient, and tax-deductible. A cost-benefit analysis has concluded that this approach would reduce morbidity, save lives, and lower health care costs (100). 2451 Crystal Drive, Suite 900 Arlington, VA 22202. However, a meta-analysis and an additional trial demonstrate that low-dose aspirin <100 mg is not effective in reducing preeclampsia. 15.7 Fasting and postprandial self-monitoring of blood glucose are recommended in both gestational diabetes mellitus and preexisting diabetes in pregnancy to achieve optimal glucose levels. These values represent optimal control if they can be achieved safely. Due to the complexity of insulin management in pregnancy, referral to a specialized center offering team-based care (with team members including maternal-fetal medicine specialist, endocrinologist or other provider experienced in managing pregnancy in women with preexisting diabetes, dietitian, nurse, and social worker, as needed) is recommended if this resource is available. Guidelines | American Association of Clinical Endocrinology The Standards of Medical Care in Diabetes2021 provides the latest in comprehensive, evidence-based recommendations for the diagnosis and treatment of children and adults with type 1, type 2, or gestational diabetes; strategies for the prevention or delay of type 2 diabetes; and therapeutic approaches that can reduce complications, mitigate cardiovascular and renal risk, and improve health outcomes. Diabetes confers significantly greater maternal and fetal risk largely related to the degree of hyperglycemia but also related to chronic complications and comorbidities of diabetes.