Egan, Aoife M.

Gestational diabetes mellitus (GDM) is a frequently observed complication of pregnancy and is associated with an elevated risk of adverse maternal and neonatal outcomes. Many women with GDM will go on to have future pregnancies, and these pregnancies may or may not be affected by GDM. We conducted a literature search, and based on data from key studies retrieved during the search, we describe the epidemiology of GDM recurrence. This includes a summary of the observed clinical risk factors of increasing maternal age, weight, ethnicity, and requirement for insulin in the index pregnancy. We then present our data from Mayo Clinic (January 2013–December 2017) which identifies a GDM recurrence rate of 47.6%, and illustrates the relevance of population-based studies to clinical practice. Lastly, we examine the available evidence on strategies to prevent GDM recurrence, and note that more research is needed to evaluate the effect of interventions before, during and after pregnancy.

AbstractBackgroundThe fasting proinsulin to insulin ratio is elevated in people with type 2 diabetes and has been suggested as a marker of β‐cell health. However, its utility in discriminating between individuals with varying degrees of β‐cell dysfunction is unclear. Proinsulin has a very different half‐life to insulin and unlike insulin does not undergo hepatic extraction prior to reaching the systemic circulation. Given these limitations, we sought to examine the relationship between fasting and postprandial concentrations of β‐cell polypeptides (proinsulin, insulin and C‐peptide) in people with normal and impaired glucose tolerance in differing metabolic environments.DesignSubjects were studied on two occasions in random order while undergoing an oral challenge. During one study day, free fatty acids were elevated (to induce insulin resistance) by infusion of Intralipid with heparin. Proinsulin to insulin and proinsulin to C‐peptide ratios were calculated for the 0‐, 30‐, 60‐ and 240‐minute time points. Insulin action (Si) and β‐cell responsivity (Φ) indices were calculated using the oral minimal model.ResultsThe fasting proinsulin to c‐peptide or fasting proinsulin to insulin ratios did not differ between groups and did not predict subsequent β‐cell responsivity to glucose during the glycerol or Intralipid study days in either group.ConclusionsAmong nondiabetic individuals, the fasting proinsulin to insulin ratio is not a useful marker of β‐cell function.

Core Outcome Sets (COS) contain an agreed minimum set of outcomes to be measured and reported in all studies in a specific area, with the objective of standardizing outcome reporting. COS may minimize research waste by identifying outcomes important to key stakeholders, allowing for improved evidence synthesis, and facilitating translation of research findings to clinical practice. Over the past 5 years, there has been significant progress in developing COS relevant to studies of diabetes in pregnancy. This review summarizes work in this area, reviews the role of patient and public involvement in COS development, and suggests areas for future research.

State-of-the-art measurement of insulin secretion in humans is accomplished by deconvolution of peripheral C-peptide concentrations using population-derived parameters of C-peptide kinetics. In contrast, knowledge of the kinetic parameters of glucagon in humans is lacking so that measurement of glucagon secretion to date is largely qualitative. This series of experiments enabled measurement of glucagon kinetics in 51 subjects, and subsequently, stepwise linear regression was used to correlate these parameters with anthropometric characteristics. This enabled the development of a population-based model using anthropometric characteristics to predict the volume of distribution and the rate of clearance. This is a necessary first step in the development of a model to quantitate of glucagon secretion and action (and its contribution to glucose tolerance) in large populations.

The Center for Disease Control and Prevention ranks diabetes mellitus (DM) as the seventh leading cause of death in the USA. The most prevalent forms of DM include Type 2 DM, Type 1 DM, and gestational diabetes mellitus (GDM). While the acute problem of diabetic hyperglycemia can be clinically managed through dietary control and lifestyle changes or pharmacological intervention with oral medications or insulin, long-term complications of the disease are associated with significant morbidity and mortality. These long-term complications involve nearly all organ systems of the body and share common pathologies associated with endothelial cell abnormalities. To better understand the molecular mechanisms underlying DM as related to future long-term complications following hyperglycemia, we have undertaken a study to determine the frequency that GDM did or did not occur in the second pregnancy of women who experienced GDM in their first pregnancy between 2013 and 2018 at Mayo Clinic, Rochester, MN. Within the five-year period of the study, the results indicate that 7,330 women received obstetrical care for pregnancy during the study period. Of these, 150 developed GDM in their first pregnancy and of these, 42 (28%) had a second pregnancy. Of these 42 women, 20 again developed GDM and 22 did not develop GDM in their second pregnancy within the study period. Following the occurrence of GDM in the first pregnancy, the study (1) established the number of women with and without GDM in the second pregnancy and (2) confirmed the feasibility to study diabetic metabolic memory using maternal placental tissue from GDM women. These studies represent Phase I of a larger research project whose goal is to analyze epigenetic mechanisms underlying true diabetic metabolic memory using endothelial cells isolated from the maternal placenta of women with and without GDM as described in this article.

Introduction Selective reporting bias, inconsistency in the chosen outcomes between trials and irrelevance of the chosen outcomes for women, limit the efficiency and value of research for prevention and treatment of gestational diabetes mellitus (GDM). One way to address these challenges is to develop core outcome sets (COSs). Methods and analysis The aim of this manuscript is to present a protocol for a study to develop COSs for GDM prevention and treatment. This is a three-phase project consisting of (1) a systematic review of the literature to create two lists of outcomes that have been reported in trials and systematic reviews of trials of interventions for the prevention and treatment of GDM, (2) a three-round, web-based e-Delphi survey with key stakeholders to prioritise these outcomes and (3) a consensus meeting to resolve any remaining disagreements and to agree on two COSs. Ethics and dissemination Ethical approval to conduct this study was obtained from the ethics committee at Galway University Hospitals on 13 December 2018 (Reference: C.A.2078). We will disseminate our research findings through peer-reviewed, open access publications and present at international conferences to reach a wide range of knowledge users.

AbstractBackgroundGestational diabetes mellitus (GDM) is highly prevalent and has both short- and long-term implications for mother and infant.Sources of dataLiterature search using PubMed with keywords ‘Gestational diabetes’ and ‘diabetes in pregnancy’ together with published papers known to the authors.Areas of agreementThe cornerstone of management is medical nutrition therapy with regular self-monitoring of capillary blood glucose levels and intensification of therapy if glycaemic goals are not achieved. Post-partum, annual assessment for type 2 diabetes is recommended.Areas of controversyDiagnostic criteria and new biomarkers for GDM and the clinical and economic benefits of treating women with milder levels of glucose intolerance during pregnancy.Growing pointsWomen with GDM are a heterogeneous group with varying degrees of insulin resistance and beta cell dysfunction.Areas timely for developing researchDevelopment of alternative diagnostic markers and application of novel technologies for GDM management.

AbstractGestational diabetes mellitus (GDM) is associated with an increased risk of adverse outcomes for mother and infant both at birth and later in life. A large body of evidence is now available relating to antenatal prevention of GDM. Overall, despite some individual trials of a variety of lifestyle interventions revealing benefit, many more have shown no effect from the second trimester onwards, even with significant gestational weight gain limitation. At‐risk women often seem reluctant to engage in lifestyle changes and frequently cannot adhere to recommended interventions even within a clinical trial setting. Many trials have not considered the heterogeneity of diabetes first discovered in pregnancy, something of importance into the future. Future work should focus on designing interventions acceptable to the population at risk, whether those taking place before or during the first trimester of pregnancy are effective, and whether greater individualization can identify those women most likely to benefit.