The top 10 priorities in adults living with type 1 diabetes in Ireland and the United Kingdom - A James Lind Alliance priority setting partnership.

AIMS: To undertake a Priority Setting Partnership (PSP), identifying the most important unanswered questions in type 1 diabetes in Ireland and the United Kingdom and to compare these to priorities identified in a 2011 PSP. METHODS: A steering committee (including eight individuals with lived experience/charity representatives and six clinicians) designed a survey which asked stakeholders to list three questions about type 1 diabetes. This was disseminated through social media, direct email contact, and printed posters. Following analysis, a second survey asked participants to rank these priorities in order of importance. The top questions were then carried forward to an online, 2 days final workshop where the final top 10 were ranked. RESULTS: There were 1050 responses (64% female, 78% adults living with type 1 diabetes, 9% healthcare professionals, 9% family members) to the first survey and 2937 individual questions were submitted. Sixty-five summary questions were submitted into a second survey, completed by 497 individuals (76% adults living with type 1 diabetes, 9% healthcare professionals, and 11% family members). Nineteen questions from the interim survey progressed to a final workshop, which identified the top 10 priorities through group discussion. As in 2011, there was emphasis on psychological health, diabetes-related complications, and hypoglycaemia. New themes prioritised included artificial intelligence and women's health. CONCLUSIONS: The research priorities, which have been identified using a robust and proven methodology, highlight the key concerns of those living with type 1 diabetes, their families and representatives, as well as clinicians in Ireland and the UK.

Maintaining glucose integrity ex-vivo: Impact of preanalytical specimen handling.

BACKGROUND: Adopting the WHO protocol for glucose analysis is arguably impractical in the routine clinical setting. Deviations may develop due to a lack of understanding regarding the impact of glycolysis on the accuracy of results. AIM: We sought to assess the stability of glucose in two different blood collection tubes (BCT), BD Vacutainer® FX 'Fl-Ox' and Greiner Vacuette® FC-Mix 'FC-Mix' stored at room temperature (RT:18-22°C) and 4°C over 8.5 days. METHOD: Each participant provided venous whole blood collected into 51 BCTs; 'Fl-Ox' (n = 26) and 'FC-Mix' (n = 25). One Fl-Ox sample from each participant was handled according to the WHO recommended method. The remaining BCTs were stored at 4°C/RT prior to analyses at designated study timepoints. Glucose was measured using the hexokinase assay on the Cobas® 8000 platform. RESULTS: Participants (n = 8, Male = 2) were aged 24-56 years. Plasma glucose measured in FI-Ox BCTs according to the WHO sample-handling method had a median concentration of 5.73 mmol/L (Range: 5.39-10.37 mmol/L). Glucose decreased by greater than minimal difference (>0.26 mmol/L) in blood collected into Fl-Ox and stored @4°C/RT within 24 h of phlebotomy. FC-Mix BCT maintained glucose <0.26 mmol/L @4°C over a period of 8.5 days and up to 4 days @RT when compared to the WHO recommended method. CONCLUSION: Glucose in FC-Mix BCT stored @4°C demonstrated the best agreement with results determined using the WHO specifications. When FC-Mix tubes were stored @RT, glucose was stable for 4 days. These findings suggest that the FC-Mix BCT effectively inhibits glycolysis and should be introduced into routine clinical practice.

Focus on Metformin: Its Role and Safety in Pregnancy and Beyond.

Metformin is used worldwide in the treatment of type 2 diabetes and has been used in the treatment of diabetes in pregnancy since the 1970s. It is highly acceptable to patients due to its ease of administration, cost and adverse effect profile. It is effective in reducing macrosomia, large-for-gestational-age infants and reduces maternal weight gain. Despite its many advantages, metformin has been associated with reductions in foetal size and has been associated with an increase in infants born small-for-gestational-age in certain cohorts. In this article, we review its efficacy, adverse effects and long-term follow-up before, during and after pregnancy for both mother and infant. We also evaluate the other forms of treatment for gestational diabetes, including oral therapies, insulin therapy and emerging treatments.

The utility of plasma glycated CD59 in predicting postpartum glucose intolerance: A prospective study of women diagnosed with GDM during a period of universal GDM screening.

AIMS: Gestational diabetes (GDM) is associated with the development of postpartum (PP) glucose intolerance. Plasma glycated CD59 (pGCD59) is an emerging biomarker for the detection of hyperglycaemia. The aim of this study was to assess the ability of PP pGCD59 to predict the development of PP GI as defined by the 2 h 75 g OGTT using the ADA criteria, in a cohort of women diagnosed with prior GDM in the index pregnancy using the 2 h 75 g OGTT at 24-28 weeks of gestation according to the World Health Organization (WHO) 2013 criteria. METHODS: Of the 2017 pregnant women recruited prospectively 140 women with gestational diabetes had samples for pGCD59 taken PP at the time of the OGTT. The ability of pGCD59 to predict the results of the PP OGTT was assessed using nonparametric receiver operating characteristic (ROC) curves. RESULTS: Women with PP glucose intolerance had significantly higher PP pGCD59 levels compared to women with normal glucose tolerance PP (3.8 vs. 2.7 SPU). PP pGCD59 identified women who developed glucose intolerance PP with an AUC of 0.80 (95% CI: 0.70-0.91). A PP pGCD59 cut-off value of 1.9 SPU generated a sensitivity of 100% (95% CI: 83.9-100), specificity of 16.9% (95% CI: 9.8-26.3), positive predictive value of 22.1% (95% CI: 21.0-22.6), and negative predictive value of 100% (95% CI: 87.4-100). PP fasting plasma glucose generated an AUC of 0.96 (95% CI: 0.89-0.99) for the identification of PP glucose intolerance. CONCLUSION: Our study found that PP pGCD9 may be a promising biomarker to identify women not requiring PP glucose intolerance screening using the traditional OGTT. While the diagnostic accuracy of pGCD59 is good, fasting plasma glucose remains a better test for the identification of PP glucose intolerance.

Attendance at pre-pregnancy care clinics for women with type 1 diabetes: A scoping review.

INTRODUCTION: Type 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. METHODS: We 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. RESULTS: There 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. CONCLUSION: This 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.

The ability of pGCD59 to predict adverse pregnancy outcomes: a prospective study of non-diabetic pregnant women in Ireland.

AIM: Even though most pregnancies are uneventful, occasionally complications do occur. Gestational diabetes is linked to an increased risk of adverse pregnancy outcomes. Early identification of women at risk of experiencing adverse outcomes, ideally through a single blood test, would facilitate early intervention. Plasma glycated CD59 (pGCD59) is an emerging biomarker which has shown promise in identifying hyperglycaemia during pregnancy and has been associated with the risk of delivering an LGA infant. The aim of this study was to explore the ability of the first- and second-trimester pGCD59 to predict adverse pregnancy outcomes. METHODS: This was a prospective study of 378 pregnant women. Samples for pGCD59 were taken at the first antenatal visit and at the time of the 2 h 75 g OGTT (24-28 weeks of gestation). Adjusted receiver operating characteristic curves were used to evaluate the ability of pGCD59 to predict maternal and neonatal outcomes. RESULTS: First-trimester pGCD59 levels were higher in women with gestational diabetes who delivered a macrosomic infant (4.2 ± 0.7 vs. 3.5 ± 1.0 SPU, p < 0.01) or an LGA infant (4.3 ± 0.3 vs. 3.6 ± 1.0 SPU, p = 0.01) compared to women with GDM that did not experience these outcomes. Second-trimester pGCD59 levels were higher in women that developed polyhydramnios (2.9 ± 0.4 vs. 2.5 ± 1.1 SPU, p = 0.03). First- and second-trimester pGCD59 predicted pregnancy-induced hypertension with good accuracy (AUC:0.85, 95%CI:0.78-0.91; AUC: 0.80, 95%CI: 0.73-0.88, respectively) and neonatal hypoglycaemia with fair to good accuracy (AUC:0.77, 95%CI: 0.54-0.99, AUC:0.81, 95%CI:0.62-0.99). CONCLUSIONS: This study has shown that pGCD59 has the potential to predict adverse pregnancy outcomes. Prospective studies with a larger number of cases are necessary to fully explore and validate the potential of this emerging biomarker in predicting adverse pregnancy outcomes.

The Role of Early Pregnancy Maternal pGCD59 Levels in Predicting Neonatal Hypoglycemia-Subanalysis of the DALI Study.

CONTEXT: Neonatal hypoglycaemia (NH) is the most common metabolic problem in infants born of mothers with gestational diabetes. Plasma glycated CD59 (pGCD59) is an emerging biomarker that has shown potential in identifying women at risk of developing gestational diabetes. The aim of this study was to assess the association between early maternal levels of pGCD59 and NH. OBJECTIVE: The aim of this study was to assess the association between early pregnancy maternal levels of plasma glycated CD59 (pGCD59) and neonatal hypoglycemia (NH). METHODS: This is an observational study of pregnant women with a prepregnancy body mass index (BMI) greater than or equal to 29 screened for eligibility to participate in the Vitamin D and Lifestyle Intervention for Gestational Diabetes (DALI) trial. This analysis included 399 pregnancies. Levels of pGCD59 were measured in fasting maternal samples taken at the time of a 75-g, 2-hour oral glucose tolerance test performed in early pregnancy (< 20 weeks). NH, the study outcome, was defined as a heel-prick capillary glucose level of less than 2.6 mmol/L within 48 hours of delivery. RESULTS: We identified 30 infants with NH. Maternal levels of pGCD59 in early pregnancy were positively associated with the prevalence of NH (one-way analysis of variance, P < .001). The odds of NH were higher in infants from mothers in tertile 3 of pGCD59 levels compared to those from mothers in tertile 1 (odds ratio [OR]: 2.41; 95% CI, 1.03-5.63). However, this was attenuated when adjusted for maternal BMI (OR: 2.28; 95% CI, 0.96-5.43). The cross-validated area under the curve (AUC) was 0.64 (95% CI, 0.54-0.74), and adjusted for maternal BMI, age, and ethnicity, the AUC was 0.70 (95% CI, 0.56-0.78). CONCLUSION: Although pGCD59 levels in early pregnancy in women with BMI greater than or equal to 29 are associated with NH, our results indicate that this biomarker by itself is only a fair predictor of NH.

Reference intervals for clinical biochemistry and haematology tests during normal pregnancy.

BACKGROUND: Pregnancy induces physiological changes which affect biochemical and haematological parameters. As the significance of laboratory test results change throughout pregnancy, the reference interval (RI) or key result interpretive guide should be specific to pregnancy. This study sought to establish trimester-specific-RIs for routine biochemical and haematological tests in healthy white European women with singleton pregnancies with comparison to RIs for non-pregnant European adults. METHODS: A retrospective analysis of a prospective longitudinal single-centre study of healthy pregnant women conducted between November 2018 and December 2020 in a tertiary academic hospital with approximately 3000 births annually. Inclusion criteria: signed informed consent, age ≥18 years, white European, body mass index (BMI) <25 kg/m2, blood pressure <140/90mmHg, non-smoker, no previous pathology or gestational diabetes. Trimester defined as T1: up to 13 weeks + 6 days, T2: 14-27 weeks + 6 days and T3: ≥28-41 weeks + 6 days. Baseline demographics, anthropometric and laboratory measurements were recorded. In total, 31 biochemical and 10 haematological ISO15189:2012 accredited tests were measured using Roche Cobas® and Sysmex XN-9100™ analysers, respectively. RIs were established according to the International Federation of Clinical Chemistry (IFCC) recommended method. RESULTS: Apparently healthy pregnant women (n = 124) with bio-banked serum samples in each trimester were recruited. At the booking visit, 49.2% (n = 61) of participants were nulliparous, with median age of 34.4 (IQR: 31.3-37.3) years, gestational age of 89 (IQR: 84-93) days, BMI of 22.5 (IQR: 21.0-23.7) kg/m2 and systolic and diastolic blood pressure of 116 (110-125) mmHg and 67 (61-75) mmHg, respectively. CONCLUSIONS: Normative trimester-specific biological intervals for routinely requested biochemical and haematological medical laboratory tests were established. These RIs will be invaluable to result interpretation and the management of pregnant women.

The utility of first trimester plasma glycated CD59 (pGCD59) in predicting gestational diabetes mellitus: A prospective study of non-diabetic pregnant women in Ireland.

AIMS: To evaluate the ability of first trimester plasma glycated CD59 (pGCD59) to predict gestational diabetes mellitus (GDM) at 24-28 weeks of gestation. METHODS: Prospectively, in 378 pregnant women, GDM was diagnosed using the one step 2 h 75 g oral glucose tolerance test adjudicated by the World Health Organisation (WHO) 2013 criteria. The ability of pGCD59 to predict GDM was assessed using receiver operating characteristic (ROC) curves adjusted for maternal age, body mass index (BMI), maternal ethnicity, parity, previous GDM, family history of diabetes mellitus and week of gestation at time of pGCD59 sampling. RESULTS: pGCD59 generated an adjusted area under the curve (AUC) of (a) 0.63 (95 %CI:0.56-0.70, p < 0.001) for predicting GDM, and (b) 0.71 (95 %CI:0.62-0.79, p < 0.001 for GDM diagnosed with a fasting plasma glucose (FPG) ≥ 5.1 mmol/L. Sensitivity analysis of BMI subgroups showed that pGCD59 generated the highest AUC in the 35 kg/m2 ≤ BMI < 40 kg/m2 (AUC:0.85, 95 %CI:0.70-0.98) and BMI ≥ 40 kg/m2 (AUC:0.88, 95 %CI:0.63-0.99) categories. CONCLUSIONS: Early in pregnancy, pGCD59 may be a good predictor of GDM in women with a high BMI and a fair predictor of GDM diagnosed by an elevated FPG independent of BMI.

The Diagnostic Accuracy of Second Trimester Plasma Glycated CD59 (pGCD59) to Identify Women with Gestational Diabetes Mellitus Based on the 75 g OGTT Using the WHO Criteria: A Prospective Study of Non-Diabetic Pregnant Women in Ireland.

The aim of this study was to evaluate the ability of second trimester plasma glycated CD59 (pGCD59), a novel biomarker, to predict the results of the 2 h 75 g oral glucose tolerance test at 24−28 weeks of gestation, employing the 2013 World Health Organisation criteria. This was a prospective study of 378 pregnant women. The ability of pGCD59 to predict gestational diabetes (GDM) was assessed using adjusted ROC curves for maternal age, BMI, maternal ethnicity, parity, previous GDM, and family history of diabetes. The pGCD59 levels were significantly higher in women with GDM compared to women with normal glucose tolerance (p = 0.003). The pGCD59 generated an adjusted AUC for identifying GDM cases of 0.65 (95%CI: 0.58−0.71, p < 0.001). The pGCD59 predicted GDM status diagnosed by a fasting glucose value of 5.1 mmol/L with an adjusted AUC of 0.74 (95%CI: 0.65−0.81, p < 0.001). Analysis of BMI subgroups determined that pGCD59 generated the highest AUC in the 35 kg/m2 ≤ BMI < 40 kg/m2 (AUC: 0.84 95%CI: 0.69−0.98) and BMI ≥ 40 kg/m2 (AUC: 0.96 95%CI: 0.86−0.99) categories. This study found that second trimester pGCD59 is a fair predictor of GDM status diagnosed by elevated fasting glucose independent of BMI and an excellent predictor of GDM in subjects with a very high BMI.

Glycaemic control and novel technology management strategies in pregestational diabetes mellitus.

Introduction: Pregestational diabetes (PGDM) is an increasingly common and complex condition that infers risk to both mother and infant. To prevent serious morbidity, strict glycaemic control is essential. The aim of this review is to review the glucose sensing and insulin delivering technologies currently available for women with PGDM. Methods: We reviewed online databases for articles relating to technology use in pregnancy using a combination of keywords and MeSH headings. Relevant articles are included below. Results: A number of technological advancements have improved care and outcomes for women with PGDM. Real time continuous glucose monitoring (rtCGM) offers clear advantages in terms of infants size and neonatal intensive care unit admissions; and further benefits are seen when combined with continuous subcutaneous insulin delivery (insulin pump) and algorithms which continuously adjust insulin levels to glucose targets (hybrid closed loop). Other advancements including flash or intermittent scanning CGM (isCGM) and stand-alone insulin pumps do not confer as many advantages for women and their infants, however they are increasingly used outside of pregnancy and many women enter pregnancy already using these devices. Discussion: This article offers a discussion of the most commonly used technologies in pregnancy and evaluates their current and future roles.

Metformin for pregnancy and beyond: the pros and cons.

CONTEXT AND AIM: Metformin has been used in pregnancy since the 1970s. It is cheap, widely available and is acceptable to women. Despite its increasing use, controversy remains surrounding its benefits and risks. Metformin effectively reduces hyperglycaemia for the mother during pregnancy and it reduces rates of macrosomia and neonatal hypoglycaemia. However, concern exists surrounding an increase in the rate of SGA births and obesity in childhood. We aim to review the evidence and expert opinion behind metformin in pregnancy through to the post-partum period. METHODS: We performed a literature review of relevant studies from online databases using a combination of keywords. We also searched the references of retrieved articles for pertinent studies. RESULTS: There is strong evidence that metformin is safe in early pregnancy with no risk of congenital malformations. If used throughout pregnancy, it is likely to lead to reduced maternal weight gain and reduced insulin dose in women with type 2 diabetes. In infants, metformin reduces hypoglycaemia and macrosomia but may increase the rate of infants born SGA. There is some evidence of an increased risk of obesity and altered fat distribution in offspring. Metformin appears well tolerated in pregnancy and is more acceptable to women than insulin therapy. CONCLUSION: Due to increasing rates of maternal obesity, GDM and type 2 diabetes, metformin use in pregnancy is increasing. Overall, it appears safe and effective but further research is needed to examine mechanisms linking metformin to obesity reported during childhood in some follow-up studies.

Characteristics of pregnant women with diabetes using injectable glucose-lowering drugs in the EVOLVE study.

AIMS: To examine clinical parameters, glycemic control, folic acid supplementation, and the presence of other chronic diseases during early pregnancy in the EVOLVE study population (women with pre-existing diabetes treated with injectable glucose-lowering drugs). METHODS: Cross-sectional baseline evaluation of EVOLVE: an international, multicenter, non-interventional study investigating the safety of injectable glucose-lowering drugs in pregnant women with pre-existing type 1 (T1D) or type 2 diabetes (T2D). Data were collected at enrollment visit interviews before gestational week 16. RESULTS: In total, 2383 women from 17 mainly European countries were enrolled in the study: 2122 with T1D and 261 with T2D; mean age was 31 and 33 years, and duration of diabetes was 15 and 6 years, respectively. For women with T1D or T2D, 63% and 75%, respectively, received basal and rapid-acting insulin, 36% and 3% rapid-acting insulin only, 0.7% and 14.0% basal insulin only, 0.2% and 5.4% premix insulin, 0.0% and 1.2% injectable glucagon-like peptide-1 receptor agonist treatment without insulin. In women with T1D or T2D, respectively, during early pregnancy, 59% and 62% had HbA1c <7.0% (53 mmol/mol); 16% and 36% reported not taking folic acid before or during early pregnancy. Overall, >40% of women had ≥1 chronic concomitant condition (predominantly thyroid disease or hypertension). Retinopathy was the most commonly reported diabetic complication. The most commonly reported previous pregnancy complication was miscarriage. CONCLUSIONS: Baseline data from this large multinational population of women with pre-existing diabetes indicate that sub-optimal glycemic control, poor pregnancy planning, and chronic concomitant conditions were common in early pregnancy.

Atlantic DIP: is weight gain less than that recommended by IOM safe in obese women with gestational diabetes mellitus?

BACKGROUND/OBJECTIVES: The Institute of Medicine (IOM) recommends gestational weight gain (GWG) of 5-9 kg in women with a body mass index (BMI) ≥ 30 kg/m2. Debate continues as to whether GWG less than that recommended is safe in women with gestational diabetes mellitus (GDM). The study objective was to examine maternal and infant outcomes for obese women with GDM who lost weight or gained 0-5 kg during pregnancy. SUBJECTS/METHODS: A 7-year retrospective cohort study of pregnancy outcomes for obese women with GDM recorded in the Atlantic Diabetes in Pregnancy database was conducted. We examined pregnancy outcomes for mothers with GDM and a BMI ≥ 30 who either lost weight or gained 0-5 kg (Group 1, n = 237) and women who gained 5-9 kg (Group 2, n = 77). We further divided groups 1 and 2 into women treated by diet only (GDM-D) (n = 120) and those requiring additional treatment with insulin (GDM-I) (n = 194). RESULTS: GDM-D women in Group 1 were more likely to deliver earlier (38.9 vs 39.8 weeks, p < 0.01), to develop pregnancy induced hypertension (PIH) (15.4% v 0%; p = 0.02) or have a post-partum haemorrhage (PPH) (13.2% vs 0, p = 0.03) compared to women in Group 2. Rates of prematurity were higher in group 1 vs 2 (14.3% vs 0%, p = 0.03). However, further logistic regression analysis adjusted for smoking status, family history of diabetes, ethnicity and age determined no significant difference in maternal or infant outcomes for women in Group 1 compared to those in Group 2. CONCLUSION: In our population, weight gain less than IOM guideline appears safe and is not associated with any further increase in adverse outcomes. However, validation through a prospective study with a larger obese GDM cohort is required before the findings presented here could be recommended for routine clinical use.

Burden of chronic kidney disease and rapid decline in renal function among adults attending a hospital-based diabetes center in Northern Europe.

INTRODUCTION: This study aimed to determine the prevalence of diabetic kidney disease (DKD) and rapid renal function decline and to identify indices associated with this decline among adults attending a diabetes center in Northern Europe. RESEARCH DESIGN AND METHODS: This is a retrospective cohort study of 4606 patients who attended a diabetes center in Ireland between June 2012 and December 2016. Definition/staging of chronic kidney disease used the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 classification based on data from the most recently attended appointment. Relevant longitudinal trends and variabilities were derived from serial records prior to index visit. Rapid renal function decline was defined based on per cent and absolute rates of estimated glomerular filtration rate (eGFR) change. Multiple linear regression was used to explore the relationships between explanatory variables and per cent eGFR change. RESULTS: 42.0% (total), 23.4% (type 1 diabetes), 47.9% (type 2 diabetes) and 32.6% (other diabetes) had DKD. Rapid decline based on per cent change was more frequent in type 2 than in type 1 diabetes (32.8% vs 14.0%, p<0.001). Indices independently associated with rapid eGFR decline included older age, greater number of antihypertensives, higher log-normalized urine albumin to creatinine ratio (LNuACR), serum alkaline phosphatase, thyroid stimulating hormone, variability in systolic blood pressure and variability in LNuACR, lower glycated hemoglobin, high-density lipoprotein cholesterol and diastolic blood pressure, and lack of ACE inhibitor/angiotensin receptor blocker prescription. CONCLUSIONS: DKD (using the KDIGO 2012 classification) and rapid eGFR decline were highly prevalent among adults attending a hospital-based diabetes clinic in a predominantly Caucasian Northern European country. The burden was greater for adults with type 2 diabetes. Expected as well as potentially novel clinical predictors were identified.

Core Outcome Sets for Studies of Diabetes in Pregnancy: A Review.

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.

Performance of early pregnancy HbA1c for predicting gestational diabetes mellitus and adverse pregnancy outcomes in obese European women.

AIMS: To investigate the performance of early pregnancy HbA1c for predicting gestational diabetes mellitus (GDM) and adverse pregnancy outcomes in obese women. METHODS: Post hoc analysis using data from the Vitamin D And Lifestyle Intervention for GDM prevention trials conducted across 9 European countries (2012-2014). Pregnant women (BMI ≥ 29 kg/m2) underwent a baseline HbA1c and oral glucose tolerance tests at < 20 weeks, 24-28 weeks, and 35-37 weeks. Women with GDM were referred for treatment. RESULTS: Among the 869 women tested, the prevalence of GDM was 25.9% before 20 weeks, with a further 8.6% at 24-28 weeks. The areas under the curves for HbA1c at the two time points were 0.55 (0.50-0.59) and 0.54 (0.47-0.61), respectively. An early HbA1c ≥ 5.7% (39 mmol/mol) (N = 111) showed low sensitivity (18.2%) with 89.1% specificity for GDM before 20 weeks, at 24-28 weeks (sensitivity of 8.0% and specificity of 88.6% after excluding early GDM), and throughout gestation (sensitivity of 15.9% and specificity of 89.4%). The ≥ 5.7% (39 mmol/mol) threshold was significantly associated with concurrent GDM before 20 weeks (adjusted OR (aOR) 2.77(1.39-5.51)) and throughout gestation (aOR 1.72 (1.02-2.89)), but not adverse pregnancy outcomes. CONCLUSIONS: Early pregnancy HbA1c is of limited use for predicting either GDM or adverse outcomes in overweight/obese European women.

A core outcome set for studies of gestational diabetes mellitus prevention and treatment.

AIMS/HYPOTHESIS: The aim of this systematic review was to develop core outcome sets (COSs) for trials evaluating interventions for the prevention or treatment of gestational diabetes mellitus (GDM). METHODS: We identified previously reported outcomes through a systematic review of the literature. These outcomes were presented to key stakeholders (including patient representatives, researchers and clinicians) for prioritisation using a three-round, e-Delphi study. A priori consensus criteria informed which outcomes were brought forward for discussion at a face-to-face consensus meeting where the COS was finalised. RESULTS: Our review identified 74 GDM prevention and 116 GDM treatment outcomes, which were presented to stakeholders in round 1 of the e-Delphi study. Round 1 was completed by 173 stakeholders, 70% (121/173) of whom went on to complete round 2; 84% (102/121) of round 2 responders completed round 3. Twenty-two GDM prevention outcomes and 30 GDM treatment outcomes were discussed at the consensus meeting. Owing to significant overlap between included prevention and treatment outcomes, consensus meeting stakeholders agreed to develop a single prevention/treatment COS. Fourteen outcomes were included in the final COS. These consisted of six maternal outcomes (GDM diagnosis, adherence to the intervention, hypertensive disorders of pregnancy, requirement and type of pharmacological therapy for hyperglycaemia, gestational weight gain and mode of birth) and eight neonatal outcomes (birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, neonatal hypoglycaemia, neonatal death and stillbirth). CONCLUSIONS/INTERPRETATION: This COS will enable future GDM prevention and treatment trials to measure similar outcomes that matter to stakeholders and facilitate comparison and combination of these studies. TRIAL REGISTRATION: This study was registered prospectively with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/studies/details/686/.