Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

The Pathophysiology of Gestational Diabetes Mellitus

Objective  To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design  Systematic review and meta-analysis of cohort studies. Data sources  PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies  Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction  Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results  There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions  There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

https://www.bmj.com/content/bmj/353/bmj.i1753.full.pdf

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

Diabet. Med. 29, 844–854 (2012)



Abstract

Background  Gestational diabetes mellitus is a potentially serious condition that affects many pregnancies and its prevalence is increasing. Evidence suggests early detection and treatment improves outcomes, but this is hampered by continued disagreement and inconsistency regarding many aspects of its diagnosis.



Methods  The Vitamin D and Lifestyle Intervention for Gestational Diabetes Mellitus Prevention (DALI) research programme aims to promote pan-European standards in the detection and diagnosis of gestational diabetes and to develop effective preventive interventions. To provide an overview of the context within which the programme will be conducted and its findings interpreted, systematic searching and narrative synthesis have been used to identify and review the best available European evidence relating to the prevalence of gestational diabetes, current screening practices and barriers to screening.



Results  Prevalence is most often reported as 2–6% of pregnancies. Prevalence may be lower towards the Northern Atlantic seaboard of Europe and higher in the Southern Mediterranean seaboard. Screening practice and policy is inconsistent across Europe, hampered by lack of consensus on testing methods, diagnostic glycaemic thresholds and the value of routine screening. Poor clinician awareness of gestational diabetes, its diagnosis and local clinical guidelines further undermine detection of gestational diabetes.



Conclusions  Europe-wide agreement on screening approaches and diagnostic standards for gestational diabetes could lead to better detection and treatment, improved outcomes for women and children and a strengthened evidence base. There is an urgent need for well-designed research that can inform decisions on best practice in gestational diabetes mellitus screening and diagnosis.

/pdf/gestational-diabetes-mellitus-in-europe-prevalence-current-2gj3i29jb3.pdf

Gestational diabetes mellitus in Europe: prevalence, current screening practice and barriers to screening. A review

The clinical and public health relevance of gestational diabetes mellitus (GDM) is widely debated due to its increasing incidence, the resulting negative economic impact, and the potential for severe GDM-related pregnancy complications. Also, effective prevention strategies in this area are still lacking, and controversies exist regarding diagnosis and management of this form of diabetes. Different diagnostic criteria are currently adopted worldwide, while recommendations for diet, physical activity, healthy weight, and use of oral hypoglycemic drugs are not always uniform. In the present review, we provide an update of current insights on clinical aspects of GDM, by discussing the more controversial issues.

Gestational diabetes mellitus: an updated overview

Diabetes and pregnancy.

Summary

Aims Gestational diabetes mellitus (GDM) is associated with adverse maternal and fetal outcome. Screening for GDM is therefore recommended but the best screening method remains controversial. This prospective, randomized study compared a risk factor-based screening programme with a universally based one.



Methods Subjects were randomized at booking to one of two groups: the risk factor group had a 3-h 100-g oral glucose tolerance test (OGTT) at 32 weeks if any risk factor for GDM was present; the universal group had a 50-g glucose challenge test performed and if their plasma glucose at 1 h was ≥ 7.8 mmol/l, a formal 3-h 100-g OGTT was then performed.



Results Universal screening detected a prevalence of GDM of 2.7%, significantly more than the 1.45% detected in the risk factor screened group (P < 0.03). Universal screening facilitated earlier diagnosis than risk factor screening – mean gestation 30 ± 2.6 weeks vs. 33 ± 3.7 weeks (P < 0.05). A higher rate of spontaneous vaginal delivery at term, and lower rates of macrosomia, Caesarean section, prematurity, pre-eclampsia and admission to neonatal intensive care unit were observed in the universally screened, early diagnosis group.



Conclusions Universal screening for GDM is superior to risk factor based screening – detecting more cases, facilitating early diagnosis and is associated with improved pregnancy outcome.

M Foley

Papers

Universal vs. risk factor‐based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome