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In the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, increasing levels of glycemia were also associated with worsening outcomes (38). 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. ACOG and ADA recommend the following target levels to reduce risk of macrosomia Fasting or preprandial blood glucose values < 95 mg/dL Postprandial blood glucose values < 140 mg/dL at 1 hour and < 120 mg/dL at 2 hours Review weekly but may alter based on degree of glucose control Diet and Exercise Nutritional assessment and plan Both metformin and intensive lifestyle intervention prevent or delay progression to diabetes in women with prediabetes and a history of GDM. Diabetes-specific testing should include A1C, creatinine, and urinary albumin-to-creatinine ratio. The food plan should provide adequate calorie intake to promote fetal/neonatal and maternal health, achieve glycemic goals, and promote weight gain according to 2009 Institute of Medicine recommendations (58). Topics covered are of interest to clinically oriented physicians, researchers, epidemiologists, psychologists, diabetes care and education specialists and other health care professionals. https://doi.org/10.2337/dc22-S015. Here, we sought to synthesize evidence from empirical research . B, 15.10 When used in addition to blood glucose monitoring targeting traditional pre- and postprandial targets, real-time continuous glucose monitoring can reduce macrosomia and neonatal hypoglycemia in pregnancy complicated by type 1 diabetes. Long-acting, reversible contraception may be ideal for many women. A Insulin is the preferred agent for the management of type 2 diabetes in pregnancy. This condition is called gestational diabetes (GD).Women with GD need special care both during and after pregnancy. Concentrations of glyburide in umbilical cord plasma are approximately 5070% of maternal levels (70,71). Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes2022. B, 14.26 Women with a history of gestational diabetes mellitus should seek preconception screening for diabetes and preconception care to identify and treat hyperglycemia and prevent congenital malformations. Additionally, as A1C represents an integrated measure of glucose, it may not fully capture postprandial hyperglycemia, which drives macrosomia. Furthermore, glyburide and metformin failed to provide adequate glycemic control in separate RCTs in 23% and 2528% of women with GDM, respectively (70,71). Women in DKA who are unable to eat often require 10% dextrose with an insulin drip to adequately meet the higher carbohydrate demands of the placenta and fetus in the third trimester in order to resolve their ketosis. Prescription of prenatal vitamins (with at least 400 g of folic acid and 150 g of potassium iodide [17]) is recommended prior to conception. Given the alteration in red blood cell kinetics during pregnancy and physiological changes in glycemic parameters, A1C levels may need to be monitored more frequently than usual (e.g., monthly). 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. A major barrier to effective preconception care is the fact that the majority of pregnancies are unplanned. Management of diabetes in pregnancy: Standards of Medical Care in Diabetes2021. Postprandial monitoring is associated with better glycemic control and lower risk of preeclampsia (3133). Simple carbohydrates will result in higher postmeal excursions. Offspring with exposure to untreated GDM have reduced insulin sensitivity and -cell compensation and are more likely to have impaired glucose tolerance in childhood (52). 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 By continuing to use our website, you are agreeing to, Justice, Equity, Diversity, and Inclusion, Institutional Subscriptions and Site Licenses, Management of Gestational Diabetes Mellitus, Management of Preexisting Type 1 Diabetes and Type 2 Diabetes in Pregnancy, https://www.ncbi.nlm.nih.gov/books/NBK196392/, https://diabetesjournals.org/journals/pages/license. Pregnancy is a ketogenic state, and women with type 1 diabetes, and to a lesser extent those with type 2 diabetes, are at risk for diabetic ketoacidosis (DKA) at lower blood glucose levels than in the nonpregnant state. E A dosage of 162 mg/day may be acceptable E; currently, in the U.S., low-dose aspirin is available in 81-mg tablets. An observational cohort study that evaluated the glycemic variables reported using CGM found that lower mean glucose, lower standard deviation, and a higher percentage of time in target range were associated with lower risk of large-for-gestational-age births and other adverse neonatal outcomes (47). E, 15.21 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. 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. Ideally, the A1C target in pregnancy is <6% (42 mmol/mol) if this can be achieved without significant hypoglycemia, but the target may be relaxed to <7% (53 mmol/mol) if necessary to prevent hypoglycemia. For 82 years, the ADA has driven discovery and research to treat, manage, and prevent diabetes while working relentlessly for a cure. 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. Every day more than 4,000 people are newly diagnosed with diabetes in America. More recently, glyburide failed to be found noninferior to insulin based on a composite outcome of neonatal hypoglycemia, macrosomia, and hyperbilirubinemia (66). To minimize the occurrence of complications, beginning at the onset of puberty or at diagnosis, all girls and women with diabetes of childbearing potential should receive education about 1) the risks of malformations associated with unplanned pregnancies and even mild hyperglycemia and 2) the use of effective contraception at all times when preventing a pregnancy. The insulin requirement levels off toward the end of the third trimester with placental aging. Family planning should be discussed, including the benefits of long-acting, reversable contraception, and effective contraception should be prescribed and used until a woman is prepared and ready to become pregnant (1014). Standard care includes screening for sexually transmitted diseases and thyroid disease, recommended vaccinations, routine genetic screening, a careful review of all prescription and nonprescription medications and supplements used, and a review of travel history and plans with special attention to areas known to have Zika virus, as outlined by ACOG. 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. Simple carbohydrates will result in higher postmeal excursions. In patients with preexisting diabetes, glycemic targets are usually achieved through a combination of insulin administration and medical nutrition therapy. 1-800-DIABETES Glucose targets are fasting plasma glucose <95 mg/dL (5.3 mmol/L) and either 1-h postprandial glucose <140 mg/dL (7.8 mmol/L) or 2-h postprandial glucose <120 mg/dL (6.7 mmol/L). Women with preexisting diabetic retinopathy will need close monitoring during pregnancy to assess for progression of retinopathy and provide treatment if indicated (23). Review and counseling on the use of nicotine products, alcohol, and recreational drugs, including marijuana, is important. The international consensus on time in range (49) endorses pregnancy target ranges and goals for TIR for patients with type 1 diabetes using CGM as reported on the ambulatory glucose profile. On the basis of available evidence, statins should also be avoided in pregnancy (118). A cost-benefit analysis has concluded that this approach would reduce morbidity, save lives, and lower health care costs (112). American Diabetes Association Professional Practice Committee; 15. Absolute risk increases linearly through a womans lifetime, being approximately 20% at 10 years, 30% at 20 years, 40% at 30 years, 50% at 40 years, and 60% at 50 years (120). About the American Diabetes Association The DRI for all pregnant women recommends a minimum of 175 g of carbohydrate, a minimum of 71 g of protein, and 28 g of fiber. Although there is some heterogeneity, many RCTs and a Cochrane review suggest that the risk of GDM may be reduced by diet, exercise, and lifestyle counseling, particularly when interventions are started during the first or early in the second trimester (5355). However, there is no consensus on the structure of multidisciplinary team care for diabetes and pregnancy, and there is a lack of evidence on the impact on outcomes of various methods of health care delivery (28). Retinopathy is a special concern in pregnancy. More than 122 million Americans have diabetes or prediabetes and are striving to manage their lives while living with the disease. In light of the immediate nutritional and immunological benefits of breastfeeding for the baby, all women, including those with diabetes, should be supported in attempts to breastfeed. More About Our Partners. In two RCTs of metformin use in pregnancy for polycystic ovary syndrome, follow-up of 4-year-old offspring demonstrated higher BMI and increased obesity in the offspring exposed to metformin (73,74). If women cannot achieve these targets without significant hypoglycemia, the ADA suggests less stringent targets based on clinical experience and individualization of care. A, 15.16 Telehealth visits for pregnant women with gestational diabetes mellitus improve outcomes compared with standard in-person care. Insulin use should follow the guidelines below. 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. Join the fight with us on Facebook (American Diabetes Association), Twitter (@AmDiabetesAssn) and Instagram (@AmDiabetesAssn). 2451 Crystal Drive,Suite 900 A, 14.2 Family planning should be discussed, and effective contraception (with consideration of long-acting, reversible contraception) should be prescribed and used until a woman's treatment regimen and A1C are optimized for pregnancy. Glycemic target lower limits defined above for preexisting diabetes apply for GDM that is treated with insulin. 14.4 Women with preexisting diabetes who are planning a pregnancy should ideally be managed beginning in preconception in a multidisciplinary clinic including an endocrinologist, maternal-fetal medicine specialist, registered dietitian nutritionist, and diabetes care and education specialist, when available. However, metformin readily crosses the placenta, resulting in umbilical cord blood levels of metformin as high or higher than simultaneous maternal levels (70,71). See PREGNANCY AND ANTIHYPERTENSIVE MEDICATIONS in Section 10 Cardiovascular Disease and Risk Management (https://doi.org/10.2337/dc21-S010) for more information on managing blood pressure in pregnancy. Retinopathy is a special concern in pregnancy. Comprehensive nutrition assessment and recommendations for: Correction of dietary nutritional deficiencies, Comprehensive diabetes self-management education. 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. 190: Gestational diabetes mellitus. Not only is the prevalence of type 1 diabetes and type 2 diabetes increasing in women of reproductive age, but there is also a dramatic increase in the reported rates of gestational diabetes mellitus (GDM). Important Updates This year, the ADA revised nearly all the sections in the Standards of Care, including recommendations for diabetes screening diagnosis, prevention, evaluation, and management of comorbidities patient education technology and glycemic assessment weight management care for special populations, such as children and older people Diabetes-specific counseling should include an explanation of the risks to mother and fetus related to pregnancy and the ways to reduce risk including glycemic goal setting, lifestyle management, and medical nutrition therapy. 201: Pregestational Diabetes Mellitus, Diabetes and Reproductive Health for Girls, ACOG Committee Opinion No. Although observational studies are confounded by the association between elevated periconceptional A1C and other poor self-care behavior, the quantity and consistency of data are convincing and support the recommendation to optimize glycemia prior to conception, given that organogenesis occurs primarily at 58 weeks of gestation, with an A1C <6.5% (48 mmol/mol) being associated with the lowest risk of congenital anomalies, preeclampsia, and preterm birth (37). B, 14.10 When used in addition to self-monitoring of blood glucose targeting traditional pre- and postprandial targets, continuous glucose monitoring can reduce macrosomia and neonatal hypoglycemia in pregnancy complicated by type 1 diabetes. Given the alteration in red blood cell kinetics during pregnancy and physiological changes in glycemic parameters, A1C levels may need to be monitored more frequently than usual (e.g., monthly). Women with preexisting diabetic retinopathy will need close monitoring during pregnancy to assess for progression of retinopathy and provide treatment if indicated (24). Join us to develop and nurture an open dialogue between industry and AACE to advance patient care. A. GDM is characterized by increased risk of large-for-gestational-age birth weight and neonatal and pregnancy complications and an increased risk of long-term maternal type 2 diabetes and offspring abnormal glucose metabolism in childhood. The purposes of this document are to provide a brief overview of the understanding of GDM, review management guidelines that have been validated by appropriately conducted clinical research, and identify gaps in current knowledge toward which future research can be directed. Standards of Medical Care for Patients with Diabetes Mellitus Diabetes and Population Health 1. On the basis of available evidence, statins should also be avoided in pregnancy (106). Therefore, all women should be tested as outlined in Section 2 Classification and Diagnosis of Diabetes (https://doi.org/10.2337/dc21-S002). It demonstrated the value of real-time CGM in pregnancy complicated by type 1 diabetes by showing a mild improvement in A1C without an increase in hypoglycemia and reductions in large-for-gestational-age births, length of stay, and neonatal hypoglycemia (47). Ideally, the A1C target in pregnancy is <6% (42 mmol/mol) if this can be achieved without significant hypoglycemia, but the target may be relaxed to <7% (53 mmol/mol) if necessary to prevent hypoglycemia. The online version of the Standards of Care will continue to be annotated in real-time with necessary updates if new evidence or regulatory changes merit immediate incorporation through the living Standards of Care process. Diabetes shouldnt stop you from living a healthy life. 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. In the prospective Nurses Health Study II (NHS II), subsequent diabetes risk after a history of GDM was significantly lower in women who followed healthy eating patterns (121). We help people with diabetes thrive by fighting for their rights and developing programs, advocacy and education designed to improve their quality of life. A Other oral and noninsulin injectable glucose-lowering medications lack long-term safety data. 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. Preprandial testing is also recommended when using insulin pumps or basal-bolus therapy so that premeal rapid-acting insulin dosage can be adjusted. Breastfeeding may also confer longer-term metabolic benefits to both mother (127) and offspring (128). B, 15.11 Continuous glucose monitoring metrics may be used in addition to but should not be used as a substitute for self-monitoring of blood glucose to achieve optimal pre- and postprandial glycemic targets. Concentrations of glyburide in umbilical cord plasma are approximately 5070% of maternal levels (63,64). Glyburide was associated with a higher rate of neonatal hypoglycemia and macrosomia than insulin or metformin in a 2015 meta-analysis and systematic review (65). Complications of gestational diabetes. Antihypertensive drugs known to be effective and safe in pregnancy include methyldopa, nifedipine, labetalol, diltiazem, clonidine, and prazosin. Low-dose aspirin >100 mg is required (109111). 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. ADA - E Consensus. An observational cohort study that evaluated the glycemic variables reported using CGM found that lower mean glucose, lower standard deviation, and a higher percentage of time in target range were associated with lower risk of large-for-gestational-age births and other adverse neonatal outcomes (48). This update presents: Today, the Standards of Care is available online and is published as a supplement to the January 2021 issue of Diabetes Care. Gestational diabetes mellitus that requires medication to achieve euglycemia is often termed class A2GDM. Women in DKA who are unable to eat often require 10% dextrose with an insulin drip to adequately meet the higher carbohydrate demands of the placenta and fetus in the third trimester in order to resolve their ketosis. E, 14.27 Postpartum care should include psychosocial assessment and support for self-care. 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. There are no adequate data on optimal weight gain versus weight maintenance in women with BMI >35 kg/m2. The risk of an unplanned pregnancy outweighs the risk of any given contraception option. One study showed that care of preexisting diabetes in clinics that included diabetes and obstetric specialists improved care (28). 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 (82,83). Metformin and glyburide should not be used as first-line agents, as both cross the placenta to the fetus. The most important diabetes-specific component of preconception care is the attainment of glycemic goals prior to conception. A, 14.23 Screen women with a recent history of gestational diabetes mellitus at 412 weeks postpartum, using the 75-g oral glucose tolerance test and clinically appropriate nonpregnancy diagnostic criteria. 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). The risk for associated hypertension and other comorbidities may be as high or higher with type 2 diabetes as with type 1 diabetes, even if diabetes is better controlled and of shorter apparent duration, with pregnancy loss appearing to be more prevalent in the third trimester in women with type 2 diabetes, compared with the first trimester in women with type 1 diabetes (105,106). 15. B. In normal pregnancy, blood pressure is lower than in the nonpregnant state. Insulin is a hormone made by your pancreas that acts like a key to let blood sugar into the cells in your body for use as energy. None of the currently available human insulin preparations have been demonstrated to cross the placenta (9095). Those with elevated blood pressure measurements should have their measurements repeated on a . In the second and third trimesters, A1C <6% (42 mmol/mol) has the lowest risk of large-for-gestational-age infants (38,41,42), preterm delivery (43), and preeclampsia (1,44). 14.18 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. Genetic carrier status (based on history): Nutrition and medication plan to achieve glycemic targets prior to conception, including appropriate implementation of monitoring, continuous glucose monitoring, and pump technology, Contraceptive plan to prevent pregnancy until glycemic targets are achieved, Management plan for general health, gynecologic concerns, comorbid conditions, or complications, if present, including: hypertension, nephropathy, retinopathy; Rh incompatibility; and thyroid dysfunction, Copyright American Diabetes Association. Counseling on diabetes in pregnancy per current standards, including: natural history of insulin resistance in pregnancy and postpartum; preconception glycemic targets; avoidance of DKA/severe hyperglycemia; avoidance of severe hypoglycemia; progression of retinopathy; PCOS (if applicable); fertility in patients with diabetes; genetics of diabetes; risks to pregnancy including miscarriage, still birth, congenital malformations, macrosomia, preterm labor and delivery, hypertensive disorders in pregnancy, etc. 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. A, 15.24 Screen women with a recent history of gestational diabetes mellitus at 412 weeks postpartum, using the 75-g oral glucose tolerance test and clinically appropriate nonpregnancy diagnostic criteria. 14.19 In pregnant patients with diabetes and chronic hypertension, a blood pressure target of 110135/85 mmHg is suggested in the interest of reducing the risk for accelerated maternal hypertension A and minimizing impaired fetal growth. Furthermore, glyburide and metformin failed to provide adequate glycemic control in separate RCTs in 23% and 2528% of women with GDM, respectively (63,64). A blood sugar level of 190 milligrams per deciliter (mg/dL), or 10.6 millimoles per liter (mmol/L), indicates gestational diabetes. A cost-benefit analysis has concluded that this approach would reduce morbidity, save lives, and lower health care costs (100). Diabetes in pregnancy is associated with an increased risk of preeclampsia (107). 112). Metformin in Women With Type 2 Diabetes in Pregnancy Trial (MiTy). 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%. 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. Hypoglycemia in pregnancy is as defined and treated in Recommendations 6.96.14 (Section 6 Glycemic Targets, https://doi.org/10.2337/dc21-S006). Review and counseling on the use of nicotine products, alcohol, and recreational drugs, including marijuana, is important. Ensure treatment decisions are timely, rely on evidence-basedguidelines, and are made . 11 Once women achieve and maintain good glycemic control, the frequency of testing can be decreased. Thus, although A1C may be useful, it should be used as a secondary measure of glycemic control in pregnancy, after self-monitoring of blood glucose. Medical nutrition therapy for GDM is an individualized nutrition plan developed between the woman and an RD/RDN familiar with the management of GDM (60,61). Patterns of glycemia in normal pregnancy: should the current therapeutic targets be challenged? The American Diabetes Association (ADA) suggests the following options: 4 ounces (1/2 cup) of juice or regular soda, 8 ounces (1 cup) of skim milk, or 5 to 6 hard candies (eg, Life-Savers); glucose tablets can also be used (check package for grams per tablet as content varies). Several studies have shown improved diabetes and pregnancy outcomes when care has been delivered from preconception through pregnancy by a multidisciplinary group focused on improved glycemic control (2528). Adjusting for BMI attenuated this association moderately, but not completely. Insulin sensitivity increases dramatically with delivery of the placenta. A. C, 14.22 A contraceptive plan should be discussed and implemented with all women with diabetes of reproductive potential. In the absence of unequivocal hyperglycemia, a positive screen for diabetes requires two abnormal values. It may be suited for pregnancy because the predict low glucose threshold for suspending insulin is in the range of premeal and overnight glucoses targets in pregnancy and may allow for more aggressive prandial dosing. What we do next will make us Connected for Life. Partner with Us. In the Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU) study's analyses of 7- to 9-year-old offspring, the 9-year-old offspring exposed to metformin in the Auckland cohort for the treatment of GDM were heavier and had a higher waist-to-height ratio and waist circumference than those exposed to insulin (72).

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