Egan, Aoife M.

Data from transgenic rodent models suggest that glucagon acts as an insulin secretagogue by signaling through the glucagon-like peptide 1 receptor (GLP-1R) present on β-cells. However, its net contribution to physiologic insulin secretion in humans is unknown. To address this question, we studied individuals without diabetes in two separate experiments. Each subject was studied on two occasions in random order. In the first experiment, during a hyperglycemic clamp, glucagon was infused at 0.4 ng/kg/min, increasing by 0.2 ng/kg/min every hour for 5 h. On one day, exendin-9,39 (300 pmol/kg/min) was infused to block GLP-1R, while on the other, saline was infused. The insulin secretion rate (ISR) was calculated by nonparametric deconvolution from plasma concentrations of C-peptide. Endogenous glucose production and glucose disappearance were measured using the tracer-dilution technique. Glucagon concentrations, by design, did not differ between study days. Integrated ISR was lower during exendin-9,39 infusion (213 ± 26 vs. 191 ± 22 nmol/5 h, saline vs. exendin-9,39, respectively; P = 0.02). In the separate experiment, exendin-9,39 infusion, compared with saline infusion, also decreased the β-cell secretory response to a 1-mg glucagon bolus. These data show that, in humans without diabetes, glucagon partially stimulates the β-cell through GLP-1R.

AbstractIntroductionType 1 diabetes mellitus occurs in one in every 275 pregnancies and can result in increased morbidity and mortality for both mother and baby. Several pregnancy complications can be reduced or prevented by attendance at pre‐pregnancy care (PPC). Despite this, less than 40% of pregnant women with pre‐gestational diabetes receive formal PPC. The aim of this scoping review is to identify the barriers to PPC attendance among women with type 1 diabetes.MethodsWe conducted a scoping review by searching five databases (Ebsco, Embase, Ovid and PubMed for literature and the ProQuest for any grey/unpublished literature) for studies in English between 2000 and 2022. Studies that evaluated attendance at PPC for women with type 1 diabetes were included.ResultsThere are multiple barriers to PPC attendance, and many of these barriers have been unchanged since the 1990s. Identified barriers can be grouped under patient‐centered and clinician‐centered headings. Patient factors include knowledge and awareness, unplanned pregnancies, negative perceptions of healthcare and communication issues, unclear attendance pathways and logistical issues including time off work and childcare. Clinician factors include physician knowledge, time constraints and lack of comfort discussing pregnancy/contraception.ConclusionThis review highlights the ongoing problem of poor attendance at PPC and identifies key barriers to be addressed when developing and implementing PPC programs for women with type 1 diabetes.

Diabetic ketoacidosis (DKA) is an obstetrical emergency that is associated with an elevated risk of adverse pregnancy outcomes. This includes pregnancy loss in up to 1 in 3 cases. Due to the normal metabolic changes that occur during pregnancy, females who are pregnant are more vulnerable to DKA, and it can occur at lesser than expected degrees of hyperglycaemia. Presenting symptoms can be non-specific and include nausea and vomiting, fatigue, polydipsia, and polyuria. DKA may be the first presentation of previously undiagnosed diabetes. Therefore, high index of suspicion, along with prompt diagnosis and management, is essential. The cornerstones of management include intravenous insulin, intravenous fluids, and electrolyte replacement. Treatment generally follows the principles for DKA management outside of pregnancy, with some additional considerations. Close maternal and fetal monitoring is essential, and intensive care unit admission is typically required to adequately achieve this goal. In all situations, a thorough investigation should occur to address the underlying cause of the DKA and prevent further episodes. This review article outlines the potential etiopathogenesis, clinical presentation, and management of DKA in pregnancy.

Abstract Context Diabetic ketoacidosis (DKA) in pregnancy is an obstetric emergency with risk of maternofetal death. Objective This work aimed to evaluate DKA events in pregnant women admitted to our inpatient obstetric service, and to examine associated clinical risk factors, presentation, and pregnancy outcomes. Methods A retrospective cohort study was conducted at the Mayo Clinic, Rochester, Minnesota, USA, and included women aged 17 to 45 years who were treated for DKA during pregnancy between January 1, 2004 and December 31, 2021. Main outcome measures included maternal and fetal death along with a broad spectrum of maternal and fetal pregnancy outcomes. Results A total of 71 DKA events were identified in 58 pregnancies among 51 women, 48 (82.8%) of whom had type 1 diabetes. There were no maternal deaths, but fetal demise occurred in 10 (17.2%) pregnancies (6 miscarriages and 4 stillbirths). Maternal social stressors were frequently present (n = 30, 51.0%), and glycemic control was suboptimal (median first trimester glycated hemoglobin A1c = 9.0%). Preeclampsia was diagnosed in 17 (29.3%) pregnancies. Infants born to women with DKA were large for gestational age (n = 16, 33.3%), suffered from neonatal hypoglycemia (n = 29, 60.4%) and required intensive care unit admission (n = 25, 52.1%). Conclusion DKA is associated with a high rate of maternofetal morbidity and fetal loss. Prenatal education strategies for women with diabetes mellitus should include a strong focus on DKA prevention, and clinicians and patients should have a high index of suspicion for DKA in all pregnant women who present with symptoms that could be attributed to this condition.

Introduction Diabetes mellitus is the most common metabolic complication of pregnancy and its prevalence worldwide is rising. The number of randomised controlled trials (RCTs) being conducted in people with diabetes is also increasing. Many studies preferentially publish findings on clinical endpoints and do not report patient-reported outcomes (PROs). In studies that do include PROs, PRO reporting is often of poor quality. Methods We will conduct this systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using a combination of medical subject headings and keywords (combined using Boolean operators), we will search web-based databases (PubMed, Cochrane and EMBASE) for RCTs published in English between 2013 and 2021. Two reviewers will review titles and abstracts. We will review the full texts of any relevant abstracts and extract the following data: date of publication or recruitment period, journal of publication, country of study, multicentre or single centre, population and number of participants, type of intervention, frequency of PRO assessment and type of PRO (or PRO measurement) used. We will also record if the PRO was a primary, secondary or exploratory outcome. We will exclude reviews, observational studies, unpublished data for example, conference abstracts and trial protocols. Any published RCT that includes data on a PRO as a primary or secondary outcome will then be compared against the Consolidated Standards of Reporting Trials—Patient-Reported Outcome extension checklist, a structured and approved framework for the publication of results of PROs. Ethics and dissemination Ethical approval to conduct this study was obtained from the ethics committee at Galway University Hospitals on 24 March 2021 (CA 2592). We aim to publish our findings in a peer-reviewed journal and present our findings at national and international conferences. Systematic review registration This systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO). Registration number CRD42021234917.

In prediabetes, anthropometric characteristics as well as insulin action do not alter the hepatic response to glucagon. The postprandial suppression or lack of suppression of glucagon secretion is an important factor governing postprandial glucose tolerance independent of insulin secretion.

BackgroundPregestational diabetes mellitus (PGDM) is associated with adverse pregnancy outcomes. Studies assessing interventions to improve maternal and infant outcomes have increased exponentially over recent years. Several outcomes in this field of maternal diabetes are rare, making it difficult to synthesise evidence.ObjectivesTo collect outcomes reported in studies assessing treatment interventions in pregnant women with PGDM.Search strategyCENTRAL, Web of Science, Medline, CINAHL, Embase and ClinicalTrials.gov from their inception until 27 January 2020.Selection criteriaAny randomised controlled trial assessing treatment interventions in pregnant women with PGDM reported in English.Data collection and analysisTwo independent reviewers assessed the suitability of articles and retrieved the data. Outcomes extracted from the literature were broadly categorised into maternal, fetal/infant or other outcomes by the study advisory group.Main resultsSixty‐seven of the 1475 studies identified fulfilled the inclusion criteria. The median number of outcomes reported per study was 15 (range 1–46). The majority of studies were from North America and Europe. Insulin and metformin were the most commonly investigated pharmacological interventions. Glucose monitoring was the most assessed technological intervention. In all, 131 unique outcomes were extracted: maternal (n = 69), fetal/infant (n = 61) and other (n = 1).ConclusionsOutcome reporting in treatment interventions trials of pregnant women with PGDM is varied, making it difficult to synthesise evidence, especially for rare outcomes. Systems are needed to standardise outcome reporting in future clinical trials and so facilitate evidence synthesis in this area of maternal diabetes.RegistrationThe systematic review was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO) database (Registration number CRD42020173549).Tweetable abstractOutcome reporting is heterogeneous in intervention trials of pregnant women with diabetes existing before pregnancy.

Objective To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). Design A consensus developmental study. Setting International. Population Two hundred and five stakeholders completed the first round. Methods The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three‐round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. Main outcome measures All outcomes were extracted from the literature. Results We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester‐specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy‐induced hypertension, pre‐eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. Conclusions This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. Tweetable abstract 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.