In T2DM, periconceptional, noninsulin, second-line antidiabetes medications were not linked to major congenital malformations vs. insulin.

SOURCE CITATION: Cesta CE, Rotem R, Bateman BT, et al. Safety of GLP-1 receptor agonists and other second-line antidiabetics in early pregnancy. JAMA Intern Med. 2024;184:144-152. 38079178.

Differential contribution of alpha and beta cell dysfunction to impaired fasting glucose and impaired glucose tolerance.

AIMS/HYPOTHESIS: People with isolated impaired fasting glucose (IFG) have normal beta cell function. We hypothesised that an increased glucose threshold for beta cell secretion explains IFG. METHODS: We used graded glucose infusion to examine the relationship of insulin secretion rate (ISR) and glucagon secretion rate (GSR) with rising glucose. We studied 39 non-diabetic individuals (53 ± 2 years, BMI 30 ± 1 kg/m2), categorised by fasting glucose and glucose tolerance status. After an overnight fast, a variable insulin infusion was used to maintain glucose at ~4.44 mmol/l (07:00 to 08:30 hours). At 09:00 hours, graded glucose infusion commenced at 1 mg kg-1 min-1 and doubled every 60 min until 13:00 hours. GSR and ISR were calculated by nonparametric deconvolution from concentrations of glucagon and C-peptide, respectively. RESULTS: The relationship of ISR with glucose was linear and the threshold for insulin secretion in isolated IFG did not differ from that in people with normal fasting glucose and normal glucose tolerance. GSR exhibited a single-exponential relationship with glucose that could be characterised by G50, the change in glucose necessary to suppress GSR by 50%. G50 was increased in IFG compared with normal fasting glucose regardless of the presence of impaired or normal glucose tolerance. CONCLUSIONS/INTERPRETATION: These data show that, in non-diabetic humans, alpha cell dysfunction contributes to the pathogenesis of IFG independently of defects in insulin secretion. We also describe a new index that quantifies the suppression of glucagon secretion by glucose.

Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of ß-cell function and glucose metabolism in subjects without diabetes.

Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased ß-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied seven subjects with IFG/IGT on two occasions. On one occasion, insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG/NGT. The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and ß-cell function. Elevation of overnight fasting FFA and glucose in NFG/NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 h, Saline vs. Intralipid/glucose, P = 0.55). Although overall ß-cell function quantified by the Disposition Index was unchanged, the dynamic component of ß-cell responsivity (ϕd) was decreased by Intralipid and glucose infusion (9 ± 1 vs. 16 ± 3 10-9, P = 0.02). In people with IFG/IGT, insulin did not alter postprandial glucose concentrations or indices of ß-cell function. Endogenous glucose production and glucose disappearance were also unchanged in both groups. We conclude that acute, overnight changes in FFA, and glucose concentrations do not alter islet function or glucose metabolism in prediabetes.NEW & NOTEWORTHY This experiment studied the effect of changes in overnight concentrations of free fatty acids (FFAs) and glucose on ß-cell function and glucose metabolism. In response to elevation of these metabolites, the dynamic component of the ß-cell response to glucose was impaired. This suggests that in health overnight hyperglycemia and FFA elevation can deplete preformed insulin granules in the ß-cell.

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.

Utility of screening for silent myocardial ischaemia in diabetes with an annual electrocardiogram.

BACKGROUND AND METHODS: Asymptomatic coronary artery disease (CAD) is common in people with diabetes mellitus, but there is a lack of consensus regarding appropriate screening for the condition. We performed a 12-lead electrocardiogram (ECG) on 312 consecutive participants with diabetes mellitus attending for routine annual outpatient review in order to determine the effectiveness of a yearly ECG in screening people with diabetes for asymptomatic CAD. RESULTS: Three of 312 participants (0.96%, 95% CI 0.2%-2.78%) had a newly identified ECG abnormality. One person had newly discovered atrial fibrillation. Two people had abnormalities which prompted further investigation for asymptomatic CAD. One of these participants underwent percutaneous coronary intervention. Seventeen further participants had abnormalities on ECG which had been previously documented, the majority having been present since their diagnosis of diabetes. CONCLUSION: A low positive yield of routine annual ECG in our study does not support its use as a screening tool for asymptomatic CAD in diabetes. Our findings support advice to perform an ECG at diagnosis of diabetes and to repeat only if a person develops relevant symptoms.

Insulin secretion and action and the response of endogenous glucose production to a lack of glucagon suppression in nondiabetic subjects.

Type 2 diabetes is a disease characterized by impaired insulin secretion and defective glucagon suppression in the postprandial period. We examined the effect of impaired glucagon suppression on glucose concentrations and endogenous glucose production (EGP) at different degrees of insulin secretory impairment. The contribution of anthropometric characteristics, peripheral, and hepatic insulin action to this variability was also examined. To do so, we studied 54 nondiabetic subjects on two occasions in which endogenous hormone secretion was inhibited by somatostatin, with glucagon infused at a rate of 0.65 ng/kg/min, at 0 min to prevent a fall in glucagon (nonsuppressed day) or at 120 min to create a transient fall in glucagon (suppressed day). Subjects received glucose (labeled with [3-3H]-glucose) infused to mimic the systemic appearance of 50-g oral glucose. Insulin was infused to mimic a prandial insulin response in 18 subjects, another 18 received 80% of the dose, and the remaining 18 received 60%. EGP was measured using the tracer-dilution technique. Decreased prandial insulin resulted in greater % increase in peak glucose but not in integrated glucose concentrations attributable to nonsuppressed glucagon. The % change in integrated EGP was unaffected by insulin dose. Multivariate regression analysis, adjusted for age, sex, weight, and insulin dose, did not show a relationship between the EGP response to impaired suppression of glucagon and insulin action as measured at the time of screening by oral glucose tolerance. A similar analysis for hepatic insulin action also did not show a relationship with the EGP response. These data indicate that the effect of impaired glucagon suppression on EGP is independent of anthropometric characteristics and insulin action.NEW & NOTEWORTHY 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.

Assessment of individual and standardized glucagon kinetics in healthy humans.

Impaired glucose tolerance arises out of impaired postprandial insulin secretion and delayed suppression of glucagon. These defects occur early and independently in the pathogenesis of prediabetes. Quantification of the contribution of α-cell dysfunction to glucose tolerance has been lacking because knowledge of glucagon kinetics in humans is limited. Therefore, in a series of experiments examining the interaction of glucagon suppression with insulin secretion we studied 51 nondiabetic subjects (age = 54 ± 13 yr, BMI = 28 ± 4 kg/m2). Glucose was infused to mimic the systemic appearance of an oral challenge. Somatostatin was used to inhibit endogenous hormone secretion. 120 min after the start of the experiment, glucagon was infused at 0.65 ng/kg/min. The rise in glucagon concentrations was used to estimate its kinetic parameters [volume of distribution (Vd), half-life (t1/2), and clearance rate (CL)]. A single-exponential model provided the best fit for the data, and individualized kinetic parameters were estimated: Vd = 8.2 ± 2.7 L, t1/2 = 4 ± 1.1 min, CL = 1.4 ± 0.33 L/min. Stepwise linear regression was used to correlate Vd with BMI and sex (R2adj = 0.44), whereas CL similarly correlated with lean body mass or BSA (both R2 = 0.28). This enabled the development of a population-based model using anthropometric characteristics to predict Vd and CL. These data demonstrate that it is feasible to derive glucagon kinetic parameters from anthropometric characteristics, thereby enabling quantitation of the rate of glucagon appearance in the systemic circulation in large populations.NEW & NOTEWORTHY 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.

Limitations of the fasting proinsulin to insulin ratio as a measure of ß-cell health in people with and without impaired glucose tolerance.

BACKGROUND: The fasting proinsulin to insulin ratio is elevated in people with type 2 diabetes and has been suggested as a marker of ß-cell health. However, its utility in discriminating between individuals with varying degrees of ß-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 ß-cell polypeptides (proinsulin, insulin and C-peptide) in people with normal and impaired glucose tolerance in differing metabolic environments. DESIGN: Subjects 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 ß-cell responsivity (Φ) indices were calculated using the oral minimal model. RESULTS: The fasting proinsulin to c-peptide or fasting proinsulin to insulin ratios did not differ between groups and did not predict subsequent ß-cell responsivity to glucose during the glycerol or Intralipid study days in either group. CONCLUSIONS: Among nondiabetic individuals, the fasting proinsulin to insulin ratio is not a useful marker of ß-cell function.

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/.

Follow-up at 1 year and beyond of women with gestational diabetes treated with insulin and/or oral glucose-lowering agents: a core outcome set using a Delphi survey.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is linked with a higher lifetime risk for the development of impaired fasting glucose, impaired glucose tolerance, type 2 diabetes, the metabolic syndrome, cardiovascular disease, postpartum depression and tumours. Despite this, there is no consistency in the long-term follow-up of women with a previous diagnosis of GDM. Further, the outcomes selected and reported in the research involving this population are heterogeneous and lack standardisation. This amplifies the risk of reporting bias and diminishes the likelihood of significant comparisons between studies. The aim of this study is to develop a core outcome set (COS) for RCTs and other studies evaluating the long-term follow-up at 1 year and beyond of women with previous GDM treated with insulin and/oral glucose-lowering agents. METHODS: The study consisted of three work packages: (1) a systematic review of the outcomes reported in previous RCTs of the follow-up at 1 year and beyond of women with GDM treated with insulin and/or oral glucose-lowering agents; (2) a three-round online Delphi survey with key stakeholders to prioritise these outcomes; and (3) a consensus meeting where the final COS was decided. RESULTS: Of 3344 abstracts identified and evaluated, 62 papers were retrieved and 25/62 papers were included in this review. A total of 121 outcomes were identified and included in the Delphi survey. Delphi round 1 was emailed to 835 participants and 288 (34.5%) responded. In round 2, 190 of 288 (65.9%) participants responded and in round 3, 165 of 190 (86.8%) participants responded. In total, nine outcomes were selected and agreed for inclusion in the final COS: assessment of glycaemic status; diagnosis of type 2 diabetes since the index pregnancy; number of pregnancies since the index pregnancy; number of pregnancies with a diagnosis of GDM since the index pregnancy; diagnosis of prediabetes since the index pregnancy; BMI; post-pregnancy weight retention; resting blood pressure; and breastfeeding. CONCLUSIONS/INTERPRETATION: This study identified a COS that will help bring consistency and uniformity to outcome selection and reporting in clinical trials and other studies involving the follow-up at 1 year and beyond of women diagnosed with GDM treated with insulin and/or oral glucose-lowering agents during pregnancy.

Optimal management of gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is highly prevalent and has both short- and long-term implications for mother and infant. SOURCES OF DATA: Literature search using PubMed with keywords 'Gestational diabetes' and 'diabetes in pregnancy' together with published papers known to the authors. AREAS OF AGREEMENT: The 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 CONTROVERSY: Diagnostic criteria and new biomarkers for GDM and the clinical and economic benefits of treating women with milder levels of glucose intolerance during pregnancy. GROWING POINTS: Women with GDM are a heterogeneous group with varying degrees of insulin resistance and beta cell dysfunction. AREAS TIMELY FOR DEVELOPING RESEARCH: Development of alternative diagnostic markers and application of novel technologies for GDM management.

The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1ß.

Myeloid angiogenic cells (MACs) promote revascularization through the paracrine release of angiogenic factors and have been harnessed as therapeutic cells for many ischemic diseases. However, their proangiogenic properties have been suggested to be diminished in diabetes. This study investigates how the diabetic milieu affects the immunophenotype and function of MACs. Both MACs isolated from diabetic conditions and healthy cells exposed to a diabetic environment were used to determine the potential of MACs as a cell therapy for diabetic-related ischemia. MACs were isolated from human peripheral blood and characterized alongside proinflammatory macrophages M (LPS + IFNγ) and proangiogenic macrophages M (IL4). Functional changes in MACs in response to high-d-glucose were assessed using an in vitro 3D-tubulogenesis assay. Phenotypic changes were determined by gene and protein expression analysis. Additionally, MACs from type 1 diabetic (T1D) patients and corresponding controls were isolated and characterized. Our evidence demonstrates MACs identity as a distinct macrophage subtype that shares M2 proangiogenic characteristics, but can be distinguished by CD163hi expression. High-d-glucose treatment significantly reduced MACs proangiogenic capacity, which was associated with a significant increase in IL1ß mRNA and protein expression. Inhibition of IL1ß abrogated the antiangiogenic effect induced by high-d-glucose. IL1ß was also significantly upregulated in MACs isolated from T1D patients with microvascular complications compared to T1D patients without microvascular complications or nondiabetic volunteers. This study demonstrates that Type 1 diabetes and diabetic-like conditions impair the proangiogenic and regenerative capacity of MACs, and this response is mediated by IL-1ß. Stem Cells 2018;36:834-843.

Planned birth at or near term for improving health outcomes for pregnant women with pre-existing diabetes and their infants.

BACKGROUND: Pregnant women with pre-existing diabetes (Type 1 or Type 2) have increased rates of adverse maternal and neonatal outcomes. Current clinical guidelines support elective birth, at or near term, because of increased perinatal mortality during the third trimester of pregnancy.This review replaces a review previously published in 2001 that included "diabetic pregnant women", which has now been split into two reviews. This current review focuses on pregnant women with pre-existing diabetes (Type 1 or Type 2) and a sister review focuses on women with gestational diabetes. OBJECTIVES: To assess the effect of planned birth (either by induction of labour or caesarean birth) at or near term gestation (37 to 40 weeks' gestation) compared with an expectant approach, for improving health outcomes for pregnant women with pre-existing diabetes and their infants. The primary outcomes relate to maternal and perinatal mortality and morbidity. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (15 August 2017), and reference lists of retrieved studies. SELECTION CRITERIA: We planned to include randomised trials (including those using a cluster-randomised design) and non-randomised trials (e.g. quasi-randomised trials using alternate allocation) which compared planned birth, at or near term, with an expectant approach for pregnant women with pre-existing diabetes. DATA COLLECTION AND ANALYSIS: Two of the review authors independently assessed study eligibility. In future updates of this review, at least two of the review authors will extract data and assess the risk of bias in included studies. We will also assess the quality of the evidence using the GRADE approach. MAIN RESULTS: We identified no eligible published trials for inclusion in this review.We did identify one randomised trial which examined whether expectant management reduced the incidence of caesarean birth in uncomplicated pregnancies of women with gestational diabetes (requiring insulin) and with pre-existing diabetes. However, published data from this trial does not differentiate between pre-existing and gestational diabetes, and therefore we excluded this trial. AUTHORS' CONCLUSIONS: In the absence of evidence, we are unable to reach any conclusions about the health outcomes associated with planned birth, at or near term, compared with an expectant approach for pregnant women with pre-existing diabetes.This review demonstrates the urgent need for high-quality trials evaluating the effectiveness of planned birth at or near term gestation for pregnant women with pre-existing (Type 1 or Type 2) diabetes compared with an expectant approach.

Planned birth at or near term for improving health outcomes for pregnant women with gestational diabetes and their infants.

BACKGROUND: Gestational diabetes is a type of diabetes that occurs during pregnancy. Women with gestational diabetes are more likely to experience adverse health outcomes such as pre-eclampsia or polyhydramnios (excess amniotic fluid). Their babies are also more likely to have health complications such as macrosomia (birthweight > 4000 g) and being large-for-gestational age (birthweight above the 90th percentile for gestational age). Current clinical guidelines support elective birth, at or near term in women with gestational diabetes to minimise perinatal complications, especially those related to macrosomia.This review replaces a review previously published in 2001 that included "diabetic pregnant women", which has now been split into two reviews. This current review focuses on pregnant women with gestational diabetes and a sister review focuses on women with pre-existing diabetes (Type 1 or Type 2). OBJECTIVES: To assess the effect of planned birth (either by induction of labour or caesarean birth), at or near term (37 to 40 weeks' gestation) compared with an expectant approach for improving health outcomes for women with gestational diabetes and their infants. The primary outcomes relate to maternal and perinatal mortality and morbidity. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (15 August 2017), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised trials comparing planned birth, at or near term (37 to 40 weeks' gestation), with an expectant approach, for women with gestational diabetes. Cluster-randomised and non-randomised trials (e.g. quasi-randomised trials using alternate allocation) were also eligible for inclusion but none were identified. DATA COLLECTION AND ANALYSIS: Two of the review authors independently assessed study eligibility, extracted data and assessed the risk of bias of the included study. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: The findings of this review are based on a single trial involving 425 women with gestational diabetes. The trial compared induction of labour with expectant management (waiting for the spontaneous onset of labour in the absence of any maternal or fetal issues that may necessitate birth) in pregnant women with gestational diabetes at term. We assessed the overall risk of bias as being low for most domains, apart from performance, detection and attrition bias (for outcome perineum intact), which we assessed as being at high risk. It was an open-label trial, and women and healthcare professionals were not blinded.There were no clear differences between women randomised to induction of labour and women randomised to expectant management for maternal mortality or serious maternal morbidity (risk ratio (RR) 1.48, 95% confidence interval (CI) 0.25 to 8.76, one trial, 425 women); caesarean section (RR 1.06, 95% CI 0.64 to 1.77, one trial, 425 women); or instrumental vaginal birth (RR 0.81, 95% CI 0.45 to 1.46, one trial, 425 women). For the primary outcome of maternal mortality or serious maternal morbidity, there were no deaths in either group and serious maternal morbidity related to admissions to intensive care unit. The quality of the evidence contributing to these outcomes was assessed as very low, mainly due to the study having high risk of bias for some domains and because of the imprecision of effect estimates.In relation to primary neonatal outcomes, there were no perinatal deaths in either group. The quality of evidence for this outcome was judged as very low, mainly due to high risk of bias and imprecision of effect estimates. There were no clear differences in infant outcomes between women randomised to induction of labour and women randomised to expectant management: shoulder dystocia (RR 2.96, 95% CI 0.31 to 28.21, one trial, 425 infants, very low-quality evidence); large-for-gestational age (RR 0.53, 95% CI 0.28 to 1.02, one trial, 425 infants, low-quality evidence).There were no clear differences between women randomised to induction of labour and women randomised to expectant management for postpartum haemorrhage (RR 1.17, 95% CI 0.53 to 2.54, one trial, 425 women); admission to intensive care unit (RR 1.48, 95% CI 0.25 to 8.76, one trial, 425 women); and intact perineum (RR 1.02, 95% CI 0.73 to 1.43, one trial, 425 women). No infant experienced a birth trauma, therefore, we could not draw conclusions about the effect of the intervention on the outcomes of brachial plexus injury and bone fracture at birth. Infants of women in the induction-of-labour group had higher incidences of neonatal hyperbilirubinaemia (jaundice) when compared to infants of women in the expectant-management group (RR 2.46, 95% CI 1.11 to 5.46, one trial, 425 women).We found no data on the following prespecified outcomes of this review: postnatal depression, maternal satisfaction, length of postnatal stay (mother), acidaemia, intracranial haemorrhage, hypoxia ischaemic encephalopathy, small-for-gestational age, length of postnatal stay (baby) and cost.The authors of this trial acknowledge that it is underpowered for their primary outcome of caesarean section. The authors of the trial and of this review note that the CIs demonstrate a wide range, therefore making it inappropriate to draw definite conclusions. AUTHORS' CONCLUSIONS: There is limited evidence to inform implications for practice. The available data are not of high quality and lack power to detect possible important differences in either benefit or harm. There is an urgent need for high-quality trials evaluating the effectiveness of planned birth at or near term gestation for women with gestational diabetes compared with an expectant approach.

A core outcome set for studies evaluating the effectiveness of prepregnancy care for women with pregestational diabetes.

AIMS/HYPOTHESIS: The aim of this study was to develop a core outcome set (COS) for trials and other studies evaluating the effectiveness of prepregnancy care for women with pregestational (pre-existing) diabetes mellitus. METHODS: A systematic literature review was completed to identify all outcomes reported in prior studies in this area. Key stakeholders then prioritised these outcomes using a Delphi study. The list of outcomes included in the final COS were finalised at a face-to-face consensus meeting. RESULTS: In total, 17 outcomes were selected and agreed on for inclusion in the final COS. These outcomes were grouped under three domains: measures of pregnancy preparation (n = 9), neonatal outcomes (n = 6) and maternal outcomes (n = 2). CONCLUSIONS/INTERPRETATION: This study identified a COS essential for studies evaluating prepregnancy care for women with pregestational diabetes. It is advocated that all trials and other non-randomised studies and audits in this area use this COS with the aim of improving transparency and the ability to compare and combine future studies with greater ease.

Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe.

AIMS/HYPOTHESIS: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. METHODS: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. RESULTS: The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24-28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35-37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. CONCLUSIONS/INTERPRETATION: The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies.

In-hospital metabolic regulation in patients with a diabetic foot ulcer: is it worthwhile?

It is well established that hyperglycaemia is associated with many negative cardiovascular and immunological effects. Because of the high prevalence of underlying vascular disease along with associated infection, patients with diabetic foot ulcers are especially vulnerable to these adverse consequences. While studies consistently demonstrate worse outcomes in the setting of hyperglycaemia during hospitalization, multiple trials examining the effects of intensive glycaemic control reveal mixed results. In particular, effects on mortality are varied, and although there may be some benefit in the setting of infection, hypoglycaemia is a concern when glucose levels are treated down to the normoglycaemic range. Therefore, although metabolic regulation is worthwhile theoretically, the optimal intensity of control is unclear. There is a need for future research to clarify the benefits and risks associated with strict metabolic control in patients with diabetic foot ulceration. In the interim recommendations from international guidelines should be followed; these advise pre-meal glucose targets of <7.8 mmol/L and random targets of <10.0 mmol/L in general medical and surgical settings.

Diagnosis and Treatment of Hyperglycemia in Pregnancy: Type 2 Diabetes Mellitus and Gestational Diabetes.

Hyperglycemia in pregnancy due to pre-existing Type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) is rising globally with increasing rates of risk factors for metabolic disease. This review summarizes current evidence and recommendations from national and international guidelines for diagnosis and management of T2DM and GDM to optimize maternal and neonatal outcomes.