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Diabetes in pregnancy

Introduction

Maternal diabetes is a significant cause of short-term and long-term morbidity for the infant and the mother, and increases in the prevalence of diabetic pregnancies have been noted in recent years. This special collection comprises selected recent full-text articles from the Springer Nature portfolio that focus on this important topic. Topics covered include pathophysiology and risk factors, appropriate screening and diagnostic testing, intervention strategies to manage and prevent gestational diabetes, and management approaches for pregnant women with pre-existing type 1 and type 2 diabetes. Over time this collection will be enhanced by the addition of specially commissioned articles and resources that provide further guidance to healthcare practitioners, as well as selected full-text articles sourced from other prominent publishers

Contents

  1. Pathophysiology and risk factors
  2. Epidemiology
  3. Screening and diagnosis
  4. Outcomes and complications
  5. Prevention and management

Instructions

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  • Access the content via the blue title text.


Pathophysiology and risk factors

Gestational diabetes mellitus: Risks and management during and after pregnancy

This review article discusses current evidence for the importance of gestational diabetes mellitus, opportunities to reduce risk to mother and child and recommendations for clinical care.

Summary points
  • Gestational diabetes mellitus (GDM) is caused by reduced pancreatic β-cell function, which results from the full spectrum of causes of β-cell dysfunction in young women.
  • GDM is associated with a modest increase in adverse perinatal outcomes, an increased risk of obesity in offspring and a high risk of subsequent development of diabetes mellitus in mothers.
  • GDM is treated nutritionally; insulin or oral antidiabetic agents can be added if maternal glucose levels and/or fetal growth parameters indicate a sufficiently high risk of perinatal complications.
  • Long-term management of mothers includes assessment of the level and type of diabetes risk, and lifestyle and/or pharmacological approaches for women at risk of type 2 diabetes mellitus.
  • Long-term management of offspring should focus on detection and mitigation of the development of obesity and its complications.
  • A great need exists for high-quality clinical evidence to determine optimal approaches for the management of GDM during and after pregnancy.

Buchanan TA et al. Nat Rev Endocrinol 2012; 8: 639–649. doi: 10.1038/nrendo.2012.96

Genetics of gestational diabetes mellitus and maternal metabolism

New progress has been made in defining the genetic architecture of gestational diabetes mellitus and maternal metabolism during pregnancy. This review highlights recent developments in the area.

Summary points
  • Women with a history of gestational diabetes mellitus (GDM) are at long-term risk for developing type 2 diabetes (T2DM), raising the question to what extent GDM and T2DM share a common genetic architecture.
  • Meta-analysis of candidate gene studies and genome-wide association analysis (GWAS) have identified a number of genes which are reproducibly associated with GDM, including TCF7L2, GCK, KCNJ11, KCNQ1, CDKAL1, IGF2BP2, MTNR1B, and IRS1, loci that are also associated with risk of T2DM.
  • The majority of these genes encode proteins important for beta cell function or development.
  • Candidate gene and GWAS have also identified genes associated with maternal metabolic traits, most of which are also associated with metabolic traits in the general population.
  • Two genes, BACE2 and HKDC1, are uniquely associated with maternal metabolic traits.
  • Taken as a whole, available data suggest that there are similarities and differences between the genetic architecture of GDM and T2DM and metabolic quantitative traits in pregnant and non-pregnant populations.

Lowe Jr WL et al. Curr Diab Rep 2016; 16: 15. doi: 10.1007/s11892-015-0709-z

β-cell adaptation in pregnancy

This article provides an overview of how glucose metabolism changes during pregnancy, how β-cells adapt to these changes, and what happens when adaptation fails and gestational diabetes ensues.

Summary points
  • During pregnancy, the proper growth and development of the fetus depends on appropriate nutrient flow from mother to fetus across the placenta.
  • In the later stages of pregnancy, the growing fetus diverts an increasing fraction of maternal glucose across the placenta, thus lowering glucose in the maternal circulation.
  • In counterbalance to the fetal glucose diversion, the placenta secretes hormones that increase maternal insulin resistance and hepatic glucose production.
  • The pancreas anticipates the increase in insulin resistance that occurs late in pregnancy by increasing β-cell numbers and function earlier in pregnancy.
  • In rodents, this β-cell expansion depends on secreted placental lactogens that signal through the prolactin receptor.
  • At the end of pregnancy, the β-cell population contracts back to its pre-pregnancy size.
  • Women with gestational diabetes may have a pregnancy-specific defect in the placental-β-cell axis.

Baeyens L et al. Diabetes Obes Metab 2016; 18(Suppl 1): 63–70. doi: 10.1111/dom.12716

Risk factors for gestational diabetes: Is prevention possible?

This review provides an overview of emerging diet, lifestyle, and other factors that may help to prevent gestational diabetes mellitus, and the challenges associated with prevention.

Summary points
  • Well-documented risk factors for gestational diabetes mellitus (GDM) include advanced maternal age, family history of diabetes, previous GDM, having a macrosomic baby, non-Caucasian race/ethnicity, being overweight or obese and cigarette smoking.
  • Genetic factors have also been implicated in the etiology of GDM; a number of candidate genes have been identified.
  • In addition to these, research in the past decade from observational studies has identified diet and lifestyle factors that are associated with GDM risk.
  • Data from at least seven observational epidemiological studies provided evidence that increased recreational physical activity before and/or during pregnancy were related to a lower GDM risk.
  • In addition to physical activity, dietary factors both during and before pregnancy are related to GDM risk.
  • Findings from intervention studies on the effect of diet and lifestyle on the prevention of GDM have been largely controversial and inconsistent.
  • Large-scale multiple-arm lifestyle intervention studies are needed.

Zhang C et al. Diabetologia 2016; 59: 1385–1390. doi: 10.1007/s00125-016-3979-3


Epidemiology

Prevalence of gestational diabetes and risk of progression to type 2 diabetes: A global perspective

This review provides an overview of the global prevalence of gestational diabetes mellitus based on data published in the past decade and discusses the methodological challenges in estimating the global burden.

Summary points
  • Gestational diabetes mellitus (GDM) has been related to substantial short- and long-term adverse health outcomes.
  • However, easily accessible and systematically organized data on estimates of global prevalence of GDM are lacking.
  • A review of publications during the past decade demonstrates large variations of the prevalence of GDM worldwide, with it being higher among Middle East and North Africa, Southeast Asia, and Western Pacific regions, whereas it is lowest in Europe.
  • Direct comparisons across countries are challenging, however, at least partly due to varied screening approaches, diagnostic criteria, and underlying population characteristics.
  • Data on the risk of progression from GDM to type 2 diabetes are still limited and little is known about modifiable factors that may lower the risk.
  • Collaborative and continuing efforts to acquire global GDM prevalence data within and across countries are needed.

Zhu Y, Zhang C. Curr Diab Rep 2016; 16: 7. doi: 10.1007/s11892-015-0699-x

Trends in the incidence of diabetes, its clinical sequelae, and associated costs in pregnancy

The aim of this retrospective claims analysis was to evaluate health outcomes, medical costs, risks and types of complications associated with diabetes in pregnancy for mothers and newborns.

Summary points
  • Increasing diabetes prevalence affects a substantial number of pregnant women in the United States.
  • Complications known to arise from the effects of maternal diabetes during the first trimester primarily include miscarriage and congenital malformation; complications that arise during the second and third trimesters primarily include stillbirth and macrosomia.
  • Maternal complications occur more commonly in women with diabetes and include hypoglycemia, gestational hypertension/preeclampsia and Cesarean delivery, among other comorbidities.
  • The aim of this study was to evaluate costs, risk and types of complications associated with diabetes in pregnancy via a large claims database analysis.
  • Adverse pregnancy outcomes, maternal complications and neonatal complications appear significantly more frequently in association with diabetes.
  • Costs of healthcare, including pharmacy, inpatient and outpatient expenses, are also higher in pregnancies complicated by diabetes.

Jovanovič L et al. Diabetes Metab Res Rev 2015; 31: 707–716. doi: 10.1002/dmrr.2656


Screening and diagnosis

Evaluation of the impact of universal testing for gestational diabetes mellitus on maternal and neonatal health outcomes: A retrospective analysis

This retrospective six-year analysis of birth data from Bradford Royal Infirmary, United Kingdom, shows that universally offering an oral glucose tolerance test was associated with increased identification of women with gestational diabetes mellitus.

Summary points
  • Treatment of gestational diabetes mellitus (GDM) seems to improve perinatal outcomes, although the relative effectiveness of different strategies for identifying women with GDM is less clear.
  • This paper describes a retrospective evaluation of the impact on maternal and neonatal outcomes of a change in policy from selective risk factor-based offering to universal offering of an oral glucose tolerance test (OGTT) to identify women with GDM.
  • The proportion of the whole obstetric population diagnosed with GDM increased almost fourfold following universal offering of an OGTT compared to selective offering of an OGTT.
  • The proportion identified as having severe hyperglycemia doubled following the change in policy.
  • However, the population case-detection rate (for both GDM and severe hyperglycemia in those with GDM) reduced by 50-60% following universal offering of a diagnostic OGTT, reflecting an increase in those offered the test who were not at risk.
  • Offering all women diagnostic testing was also associated with improved neonatal outcomes in women identified with GDM.

Farrar D et al. BMC Pregnancy Childbirth 2014; 14: 317. doi: 10.1186/1471-2393-14-317

Gestational diabetes testing: Making sense of the controversy

This review describes the current state of knowledge about the impact of hyperglycemia in pregnancy and discusses the various approaches to testing for gestational diabetes mellitus and the evidence to support them.

Summary points
  • There continues to be controversy over exactly who, when, and how to test for gestational diabetes mellitus (GDM), with various professional organizations and experts in the field suggesting different strategies.
  • Controversies in GDM testing include one-step versus two-step testing, Carpenter-Coustan criteria versus National Diabetes Data Group thresholds, universal versus risk-based screening, whether to screen early in pregnancy, management of a single abnormal value on a 3-hour glucose tolerance test, and the use of hemoglobin A1c for screening.
  • GDM testing controversies are centered on different providers’ preferences for sensitivity or specificity, which are likely to be influenced by provider experience, patient populations, and resources.
  • The approach to GDM testing should be the most sensitive testing strategy feasible for a given woman in a given practice.

Salmeen K. J Midwifery Women's Health 2016; 61: 203–209. doi: 10.1111/jmwh.12377


Outcomes and complications

Identifying key intervention opportunities during a pregnancy complicated by diabetes: A review of acute complications of diabetes during pregnancy

A clinical overview of common complications in diabetes during pregnancy and strategies for implementing interventional patient care.

Summary points
  • Diabetes during pregnancy automatically categorizes a pregnancy as a high risk.
  • Current guidelines recommend testing women for overt diabetes (type 1, type 2, or pre-diabetes) at the first prenatal visit.
  • Diabetic retinopathy and nephropathy are well known to progress during pregnancy and should be followed closely.
  • Complications such as preeclampsia and hypertension have a strong association with diabetes during pregnancy, and other rare but acute complications including venous thromboembolism, cardiovascular disease (CVD), sepsis, and diabetic ketoacidosis can also occur.
  • Diabetes during pregnancy also increases the risk of labor and delivery complications such as induction of labor and cesarean section.
  • Post-partum changes and stress have the ability to exacerbate diabetes complications and may lead to unexpected challenges such as delayed onset of lactation.
  • Post-partum care should include the development of a life plan, as patients with diabetes during pregnancy may be at greatest risk of developing CVD, and those with gestational diabetes are more likely to go on to develop type 2 diabetes.

Bradley PK et al. Curr Diab Rep 2016; 16: 17. doi: 10.1007/s11892-015-0710-6

Quantification of the type 2 diabetes risk in women with gestational diabetes: A systematic review and meta-analysis of 95,750 women

A systemic review of the factors that increase the risk of developing type 2 diabetes in women with gestational diabetes.

Summary points
  • Up to half of women with gestational diabetes mellitus (GDM) go on to develop type 2 diabetes.
  • The objective of this systematic review was to quantify the risk of progression to type 2 diabetes for women with GDM.
  • The future risk of diabetes appears to be mainly influenced by the gestational glycemic status, as women with increased fasting blood glucose level and those who required insulin to manage GDM were more likely to develop type 2 diabetes.
  • Hypertensive disorders in pregnancy and preterm delivery in GDM pregnancies are associated with future onset of type 2 diabetes.
  • Factors specific to pregnancy such as gestational age at onset of GDM and general maternal characteristics such as body mass index, ethnicity and family history are also associated with future onset of type 2 diabetes.
  • Postnatal counseling of women with GDM should be individualized to reduce the risk of developing type 2 diabetes later in life.

Rayanagoudar G et al. Diabetologia 2016; 59: 1403–1411. doi: 10.1007/s00125-016-3927-2

Long-term health outcomes in offspring born to women with diabetes in pregnancy

This review critically assesses the existence of a direct causal relationship between diabetes during pregnancy and long-term offspring health outcomes.

Summary points
  • Diabetes in pregnancy includes pre-existing type 1 diabetes (present before pregnancy), pre-existing type 2 diabetes, or gestational diabetes (ie, diabetes with onset or first diagnosis in pregnancy).
  • Intra-uterine mechanisms make an important contribution to the link between gestational diabetes and offspring greater adiposity, insulin resistance, and type 2 diabetes.
  • The role of maternal diabetes and cognitive abilities of offspring remains unclear, as some studies report an adverse effect, while others found that maternal pregnancy diabetes may result in a ‘protective’ effect and greater offspring IQ in childhood.
  • The putative role of DNA methylation as a mediator in associations of pregnancy diabetes and offspring long-term health is promising but still novel.
  • Current evidence supports a direct causal role for exposure to maternal diabetes in utero in determining offspring long-term greater adiposity and adverse cardiometabolic health.

Fraser A, Lawlor DA. Curr Diab Rep 2014; 14: 489. doi: 10.1007/s11892-014-0489-x

Stillbirth in the pregnancy complicated by diabetes

A review of the epidemiology, pathophysiology, prevention, and ongoing research into diabetes-associated perinatal mortality.

Summary points
  • Despite improvements in screening and patient care, approximately 4% of all stillbirths are attributable to diabetes, and diabetic pregnancies are at increased risk for perinatal mortality.
  • Recent studies have shown that patients with type 1 and type 2 diabetes have a greater risk of stillbirth, while gestational diabetes as a risk factor is still debatable.
  • Practitioners often find no clear etiology for stillbirth, as the pathophysiology of stillbirth in diabetic pregnancies is complex and appears to be multifactorial.
  • In terms of achieving pregnancy outcomes in women with diabetes that approximate those of women without diabetes, strict glycemic control is the single most important goal for women with diabetes attempting pregnancy.
  • Women with pre-existing vascular complications (eg, hypertension) should be appropriately treated with medications that are considered acceptable for pregnancy.
  • In general, women with well-controlled diabetes can be delivered at 39 weeks, while women with poorly controlled diabetes can be delivered at any time from 34 to 39 weeks.

Starikov R et al. Curr Diab Rep 2015; 15: 11. doi: 10.1007/s11892-015-0580-y


Prevention and management

Benefits and harms of treating gestational diabetes mellitus: A systematic review and meta-analysis for the US Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research

This systematic review evaluated whether treatment of gestational diabetes mellitus modifies outcomes of mothers and their offspring and whether it is associated with any harms.

Summary points
  • Outcomes of treating gestational diabetes mellitus (GDM) are not well-established.
  • To summarize evidence about the maternal and neonatal benefits and harms of treating GDM, a systematic review of trials and cohort studies published in English from 1995 to May 2012 was conducted.
  • Of 14,428 citations, five randomized controlled trials and six retrospective cohort studies met inclusion criteria. All studies compared diet modification, glucose monitoring, and insulin as needed with standard care.
  • There was moderate evidence for fewer cases of preeclampsia, shoulder dystocia, and macrosomia in the treated group.
  • Current research does not show a treatment effect of GDM on clinical neonatal hypoglycemia or future poor metabolic outcomes of the offspring.
  • There is little evidence of short-term harm of treating GDM other than an increased demand for services.

Hartling L et al. Ann Intern Med 2013; 159: 123–129. doi: 10.7326/0003-4819-159-2-201307160-00661

Management of type 1 diabetes in pregnancy

This review discusses the current standards of care and latest research for type 1 diabetes in the preconception, pregnancy, and postpartum periods.

Summary points
  • Patients with type 1 diabetes mellitus (T1DM) who are of reproductive age should be informed about the increased risks associated with pregnancy to ensure that pregnancies are planned.
  • Early counseling, pregnancy planning, good glycemic control, and a multi-specialist approach to care before and during pregnancy can all improve pregnancy outcomes for mothers with T1DM and their infants.
  • The goals of preconception care should be tight glycemic control with an A1C <7% and as close to 6% as possible without significant hypoglycemia.
  • Pregnant patients with T1DM have insufficient insulin, causing higher maternal glucose levels. Tight glycemic control should be continued throughout the pregnancy with an A1C goal <6 % to reduce the occurrence of maternal, fetal, and neonatal complications.
  • More research is needed in this patient population, especially in the areas of preconception counseling and education, ways to predict and decrease preeclampsia risk, insulin dosing with relation to meal times during pregnancy, medication use during lactation in women with T1DM, and how to improve breastfeeding rates, among others.

Feldman AZ, Brown FM. Curr Diab Rep 2016; 16: 76. doi: 10.1007/s11892-016-0765-z

Management of pregnant women with type 2 diabetes mellitus and the consequences of fetal programming in their offspring

This review examines the state of the science on preconception and pregnancy management of women with type 2 diabetes.

Summary points
  • Women with type 2 diabetes who become pregnant need preconception counseling, preconception weight management and weight loss, proper weight gain during pregnancy, self-monitoring of blood glucose levels, medication, medical nutrition therapy, and exercise.
  • It is imperative that healthcare providers focus on the health of young women and work with them to manage overweight and obesity early in life to prevent development of prediabetes and type 2 diabetes later in life.
  • Healthcare providers need to talk with young women not only about their own health status but also the future health status of their unborn baby and the risks of fetal programming.
  • Once a woman develops type 2 diabetes, a balance between weight management, optimal glycemic control, medical nutrition therapy, and exercise can create the ideal environment for the woman to conceive and optimize outcomes for her and her unborn child.
  • Prevention of fetal programming by tight glycemic control will be instrumental in breaking the cycle of obesity, diabetes, and complications.

Berry DC et al. Curr Diab Rep 2016; 16: 36. doi: 10.1007/s11892-016-0733-7

The role of lifestyle interventions in the prevention of gestational diabetes

Epidemiologic data linking healthy lifestyle choices to reduced risk of gestational diabetes mellitus (GDM) are compared with interventional trials of diet and exercise to prevent GDM.

Summary points
  • Obesity is a rising concern in women of reproductive age. Lifestyle interventions introduced in pregnancy have the potential to prevent the development of gestational diabetes mellitus (GDM) and other complications.
  • The observational literature supports a link between unhealthy lifestyle habits, obesity, and GDM and most trials of lifestyle interventions to prevent GDM have been negative.
  • Reasons for negative studies may include lack of power, lack of intervention uptake, and severity of placenta-mediated insulin resistance.
  • Dietary approaches appear to be more successful than exercise or a combination of diet and exercise at decreasing GDM.
  • Physicians should continue to recommend against excessive weight gain in pregnancy as it has been associated with large for gestational age neonates, non-elective Cesarean section, and post-partum weight retention.
  • Future studies should be powered for a reduction in GDM, monitor lifestyle changes closely, and include a psychological component in the intervention.
  • Unfortunately at this time, there is insufficient evidence to recommend for a specific lifestyle program to prevent GDM.

Halperin IJ, Feig DS. Curr Diab Rep 2014; 14: 452. doi: 10.1007/s11892-013-0452-2

The use of insulin analogs in pregnancy

A discussion of the role of insulin analogs in pregnancy and whether there are differences between women with type 1 diabetes, type 2 diabetes or gestational diabetes.

Summary points
  • Excellent glycemic control is essential in pregnancy to optimize maternal and fetal outcomes.
  • Insulin lispro and insulin aspart are safe in pregnancy and may improve post-prandial glycemic control in women with type 1 diabetes.
  • However, a lack of data indicating improved fetal outcomes would suggest that there is no imperative to switch to a short-acting analog where the woman's diabetes is well controlled with human insulin.
  • Most studies of insulin glargine in pregnancy are small, retrospective and include women with pre-existing diabetes and gestational diabetes. There appear to be no major safety concerns and so it seems reasonable to continue insulin glargine if required to achieve glycemic control.
  • The greater evidence base supports the use of insulin detemir as the first-line long-acting analog in pregnancy but the lack of definitive fetal benefits means that there is no strong need to switch a woman who is well controlled on neutral protamine Hagedorn insulin.

Lambert K, Holt RIG. Diabetes Obes Metab 2013; 15: 888–900. doi: 10.1111/dom.12098

Using oral agents to manage gestational diabetes: What have we learned?

Research suggests that glyburide and metformin alone or in conjunction with insulin may be safe for the treatment of gestational diabetes (GDM). This paper summarizes data on the use of these oral agents for GDM.

Summary points
  • Neither glyburide nor metformin are approved by the Food and Drug Administration (FDA) for use in pregnancy and both are classified as category B during pregnancy.
  • However, glyburide has become the preferred medical treatment for gestational diabetes (GDM) in the USA, surpassing insulin. Yet, many studies report significant failure rates.
  • Both a large retrospective study and a recent meta-analysis of randomized controlled trials (RCTs) indicated higher rates of macrosomia and neonatal hypoglycemia for women treated with glyburide compared with insulin.
  • A large glyburide-versus-insulin RCT with adequate power to detect neonatal and pubertal outcomes is therefore needed.
  • As glyburide crosses the placenta, additional studies are needed to evaluate the effect of exposure of the fetal pancreas to an insulin secretagogue and the long-term effects on weight and cardiometabolic status during childhood and adolescence.
  • A large, well-designed RCT of metformin versus insulin demonstrated similar outcomes between metformin and insulin-treated women with the exception of less neonatal hypoglycemia and slightly earlier gestational age at birth in the metformin group.
  • As metformin crosses the placenta, physicians need to learn more about the effect of exposure in utero to the child and adolescent.

Buschur E et al. Curr Diab Rep 2015; 15: 4. doi: 10.1007/s11892-014-0570-5

Gestational diabetes mellitus and postpartum care practices of nurse-midwives

By means of a survey of certified nurse-midwives, this study aimed to estimate the prevalence of postpartum diabetes screening and lifestyle modification counseling for women with a recent history of gestational diabetes.

Summary points
  • This study assessed the screening and counseling that Ohio certified nurse-midwives (CNMs) provide for postpartum women who have had gestational diabetes mellitus (GDM).
  • Only half of responding CNMs reported screening their postpartum patients for glucose tolerance after a GDM pregnancy.
  • Among CNMs who screen postpartum, only half reported using one of the recommended postpartum glucose tolerance tests.
  • About two-thirds of CNMs counseled women with recent histories of GDM to exercise regularly; however, only one-quarter of CNMs referred overweight or obese women with recent GDM histories to diet support groups or other nutrition counseling.
  • Midwives need to consistently screen postpartum women who have had a GDM pregnancy for glucose tolerance using either a fasting blood sugar or a 2-hour oral glucose test and to encourage these women to exercise regularly and lose weight if they are overweight or obese.

Ko JY et al. J Midwifery Women's Health 2013; 58: 33–40. doi: 10.1111/j.1542-2011.2012.00261.x