Pathophysiology from preconception, during pregnancy, and beyond.

Gestational diabetes is the most common medical complication in pregnancy. Historically, gestational diabetes was considered a pregnancy complication involving treatment of rising glycaemia late in the second trimester. However, recent evidence challenges this view. Pre-pregnancy and pregnancy-specific factors influence gestational glycaemia, with open questions regarding roles of non-glycaemic factors in the aetiology and consequences of gestational diabetes. Varying patterns of insulin secretion and resistance in early and late pregnancy underlie a heterogeneity of gestational diabetes in the timing and pathophysiological subtypes with clinical implications: early gestational diabetes and insulin resistant gestational diabetes subtypes are associated with a higher risk of pregnancy complications. Metabolic perturbations of early gestational diabetes can affect early placental development, affecting maternal metabolism and fetal development. Fetal hyperinsulinaemia can affect the development of multiple fetal tissues, with short-term and long-term consequences. Pregnancy complications are prevented by managing glycaemia in early and late pregnancy in some, but not all women with gestational diabetes. A better understanding of the pathophysiology and heterogeneity of gestational diabetes will help to develop novel management approaches with focus on improved prevention of maternal and offspring short-term and long-term complications, from pre-conception, throughout pregnancy, and beyond.

Epidemiology and management of gestational diabetes.

Gestational diabetes is defined as hyperglycaemia first detected during pregnancy at glucose concentrations that are less than those of overt diabetes. Around 14% of pregnancies globally are affected by gestational diabetes; its prevalence varies with differences in risk factors and approaches to screening and diagnosis; and it is increasing in parallel with obesity and type 2 diabetes. Gestational diabetes direct costs are US$1·6 billion in the USA alone, largely due to complications including hypertensive disorders, preterm delivery, and neonatal metabolic and respiratory consequences. Between 30% and 70% of gestational diabetes is diagnosed in early pregnancy (ie, early gestational diabetes defined by hyperglycaemia before 20 weeks of gestation). Early gestational diabetes is associated with worse pregnancy outcomes compared with women diagnosed with late gestational diabetes (hyperglycaemia from 24 weeks to 28 weeks of gestation). Randomised controlled trials show benefits of treating gestational diabetes from 24 weeks to 28 weeks of gestation. The WHO 2013 recommendations for diagnosing gestational diabetes (one-step 75 gm 2-h oral glucose tolerance test at 24-28 weeks of gestation) are largely based on the Hyperglycemia and Adverse Pregnancy Outcomes Study, which confirmed the linear association between pregnancy complications and late-pregnancy maternal glycaemia: a phenomenon that has now also been shown in early pregnancy. Recently, the Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) trial showed benefit in diagnosis and treatment of early gestational diabetes for women with risk factors. Given the diabesity epidemic, evidence for gestational diabetes heterogeneity by timing and subtype, and advances in technology, a life course precision medicine approach is urgently needed, using evidence-based prevention, diagnostic, and treatment strategies.

Cost-effectiveness of diagnosis and treatment of early gestational diabetes mellitus: economic evaluation of the TOBOGM study, an international multicenter randomized controlled trial.

Background: A recently undertaken multicenter randomized controlled trial (RCT) "Treatment Of BOoking Gestational diabetes Mellitus" (TOBOGM: 2017-2022) found that the diagnosis and treatment of pregnant women with early gestational diabetes mellitus (GDM) improved pregnancy outcomes. Based on data from the trial, this study aimed to assess the cost-effectiveness of diagnosis and treatment of early GDM (from <20 weeks') among women with risk factors for hyperglycemia in pregnancy compared with usual care (no treatment until 24-28 weeks') from a healthcare perspective. Methods: Participants' healthcare resource utilization data were collected from their self-reported questionnaires and hospital records, and valued using the unit costs obtained from standard Australian national sources. Costs were reported in US dollars ($) using the purchasing power parity (PPP) estimates to facilitate comparison of costs across countries. Intention-to-treat (ITT) principle was followed. Missing cost data were replaced using multiple imputations. Bootstrapping method was used to estimate the uncertainty around mean cost difference and cost-effectiveness results. Bootstrapped cost-effect pairs were used to plot the cost-effectiveness (CE) plane and cost-effectiveness acceptability curve (CEAC). Findings: Diagnosis and treatment of early GDM was more effective and tended to be less costly, i.e., dominant (cost-saving) [-5.6% composite adverse pregnancy outcome (95% CI: -10.1%, -1.2%), -$1373 (95% CI: -$3,749, $642)] compared with usual care. Our findings were confirmed by both the CE plane (88% of the bootstrapped cost-effect pairs fall in the south-west quadrant), and CEAC (the probability of the intervention being cost-effective ranged from 84% at a willingness-to-pay (WTP) threshold value of $10,000-99% at a WTP threshold value of $100,000 per composite adverse pregnancy outcome prevented). Sub-group analyses demonstrated that diagnosis and treatment of early GDM among women in the higher glycemic range (fasting blood glucose 95-109 mg/dl [5.3-6.0 mmol/L], 1-h blood glucose ≥191 mg/dl [10.6 mmol/L] and/or 2-h blood glucose 162-199 mg/dl [9.0-11.0 mmol/L]) was more effective and less costly (dominant) [-7.8% composite adverse pregnancy outcome (95% CI: -14.6%, -0.9%), -$2795 (95% CI: -$6,638, -$533)]; the intervention was more effective and tended to be less costly [-8.9% composite adverse pregnancy outcome (95% CI: -15.1%, -2.6%), -$5548 (95% CI: -$16,740, $1547)] among women diagnosed before 14 weeks' gestation as well. Interpretation: Our findings highlight the potential health and economic benefits from the diagnosis and treatment of early GDM among women with risk factors for hyperglycemia in pregnancy and supports its implementation. Long-term follow-up studies are recommended as a key future area of research to assess the potential long-term health benefits and economic consequences of the intervention. Funding: National Health and Medical Research Council (grants 1104231 and 2009326), Region O¨rebro Research Committee (grants Dnr OLL-970566 and OLL-942177), Medical Scientific Fund of the Mayor of Vienna (project 15,205 and project 23,026), South Western Sydney Local Health District Academic Unit (grant 2016), and Western Sydney University Ainsworth Trust Grant (2019).

The first International Association of Diabetes and Pregnancy Study Groups summit on the diagnosis of gestational diabetes in early pregnancy: TOBOGM Summit Report.

The first International Association of Diabetes and Pregnancy Study Groups Summit on the diagnosis of gestational diabetes in early pregnancy (Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) Summit) was held on the 17 November 2022 in Sydney, Australia. It sought to use the TOBOGM trial findings to scope the issues involved with early screening, to inform future discussions over possible approaches for diagnosing gestational diabetes mellitus (GDM) in early pregnancy. Most delegates supported testing for early GDM using a one-step 75 g oral glucose tolerance test approach with Canadian Diabetes Association criteria preferred, but highlighted the importance of considering resources, cost, consumer perspectives and equity in translating TOBOGM results into a clinical approach to screening for, and diagnosing, early GDM.

Regression From Early GDM to Normal Glucose Tolerance and Adverse Pregnancy Outcomes in the Treatment of Booking Gestational Diabetes Mellitus Study.

OBJECTIVE: To compare pregnancy outcomes among women with a normal oral glucose tolerance test (OGTT) before 20 weeks' gestation (early) and at 24-28 weeks' gestation (late) (no gestational diabetes mellitus, or No-GDM), those with early GDM randomized to observation with a subsequent normal OGTT (GDM-Regression), and those with GDM on both occasions (GDM-Maintained). RESEARCH DESIGN AND METHODS: Women at <20 weeks' gestation with GDM risk factors who were recruited for a randomized controlled early GDM treatment trial were included. Women with treated early GDM and late GDM (according to the World Health Organization's 2013 criteria) were excluded from this analysis. Logistic regression compared pregnancy outcomes. RESULTS: GDM-Regression (n = 121) group risk factor profiles and OGTT results generally fell between the No-GDM (n = 2,218) and GDM-Maintained (n = 254) groups, with adjusted incidences of pregnancy complications similar between the GDM-Regression and No-GDM groups. CONCLUSIONS: Women with early GDM but normal OGTT at 24-28 weeks' gestation had pregnancy outcomes that were similar to those of individuals without GDM. Identifying early GDM likely to regress would allow treatment to be avoided.

Perinatal Outcomes in Early and Late Gestational Diabetes Mellitus After Treatment From 24-28 Weeks' Gestation: A TOBOGM Secondary Analysis.

OBJECTIVE: In most gestational diabetes mellitus (GDM) studies, cohorts have included women combined into study populations without regard to whether hyperglycemia was present earlier in pregnancy. In this study we sought to compare perinatal outcomes between groups: women with early GDM (EGDM group: diagnosis before 20 weeks but no treatment until 24-28 weeks if GDM still present), with late GDM (LGDM group: present only at 24-28 weeks), and with normoglycemia at 24-28 weeks (control subjects). RESEARCH DESIGN AND METHODS: This is a secondary analysis of a randomized controlled treatment trial where we studied, among women with risk factors, early (<20 weeks' gestation) GDM defined according to World Health Organization 2013 criteria. Those receiving early treatment for GDM treatment were excluded. GDM was treated if present at 24-28 weeks. The primary outcome was a composite of birth before 37 weeks' gestation, birth weight ≥4,500 g, birth trauma, neonatal respiratory distress, phototherapy, stillbirth/neonatal death, and shoulder dystocia. Comparisons included adjustment for age, ethnicity, BMI, site, smoking, primigravity, and education. RESULTS: Women with EGDM (n = 254) and LGDM (n = 467) had shorter pregnancy duration than control subjects (n = 2,339). BMI was lowest with LGDM. The composite was increased with EGDM (odds ratio [OR] 1.59, 95% CI 1.18-2.12)) but not LGDM (OR 1.19, 95% CI 0.94-1.50). Induction of labor was higher in both GDM groups. In comparisons with control subjects there were higher birth centile, higher preterm birth rate, and higher rate of neonatal jaundice for the EGDM group (but not the LGDM group). The greatest need for insulin and/or metformin was with EGDM. CONCLUSIONS: Adverse perinatal outcomes were increased with EGDM despite treatment from 24-28 weeks' gestation, suggesting the need to initiate treatment early, and more aggressively, to reduce the effects of exposure to the more severe maternal hyperglycemia from early pregnancy.

The Effect of Weight Loss Through Lifestyle Interventions in Patients With Heart Failure With Preserved Ejection Fraction-A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) accounts for >50% of heart failure cases and is associated with significant morbidity and health system burden. To date, there have been limited treatment options proven to improve outcomes in these patients, with sodium glucose co-transporter 2 (SGLT2) inhibitors the first class of drug to demonstrate significant clinical benefits, including reductions in heart failure hospitalisation. Obesity is associated with all forms of heart failure and has been linked with worse clinical outcomes. Numerous reviews support the benefits of weight loss in heart failure, more specifically in patients with heart failure with reduced ejection fraction. However, the evidence in HFpEF patients is less clear. With limited pharmacotherapy options and growing support for weight loss in patients with HFpEF, this systematic review and meta-analysis aims to examine the effects of lifestyle interventions on weight loss and other health outcomes in patients with HFpEF. METHODS: Web of Science, Embase, Scopus, and PubMed databases were searched to identify relevant studies up to February 2023. Included studies were randomised controlled trials (with a duration of four weeks or more) of lifestyle interventions conducted in adults with HFpEF that reported weight loss. Outcomes of interest were body weight, body mass index (BMI), blood pressure (systolic and diastolic), aerobic capacity (6-minute walk distance), New York Heart Association (NYHA) Functional Classification, self-reported health quality of life (Minnesota Living with Heart Failure Questionnaire; MLHFQ), and N-terminal pro B-Type Natriuretic Peptide (NT-proBNP) levels. Review Manager software was used to conduct random effect meta-analyses, forest plots were generated for each outcome, and between-study heterogeneity was estimated using the I2 test statistic. Risk-of-bias assessment used the Cochrane risk-of-bias tool, and the certainty of the evidence was assessed using GRADE. RESULTS: From 2,282 records identified, six studies with a total of 375 participants, between three to six months in duration, were included in this systematic review and meta-analysis. Lifestyle interventions consisted of diet only, exercise only, combination of diet and exercise, and education and exercise. Over a mean follow-up of 4.5 months, pooled effects of the interventions were associated with a reduction in body weight of >5kg (weight mean difference (WMD): -5.30 kg; 95% CI: -8.72 to -1.87; p=0.002), and a reduction in resting systolic (WMD: -2.98 mmHg; 95% CI: -4.20 to -1.76; p<0.001) and diastolic blood pressure (WMD: -4.51 mmHg; 95% CI: -8.39 to -0.64; p=0.02) compared with those who received usual care. Interventions also improved 6-minute walk distance (WMD: 43.63 m; 95% CI: 22.28 to 64.97; p<0.001), NYHA class (WMD: -0.54; 95% CI: -0.75 to -0.33; p<0.001), and MLHFQ score (WMD: -17.77; 95% CL: -19.00 to -16.53; p<0.001). CONCLUSION: In patients with HFpEF, lifestyle intervention was associated with a significant reduction in body weight and had favourable effects on blood pressure, aerobic capacity, NYHA class, and health-related quality of life. Further research is needed in this population to examine the feasibility and durability of weight loss interventions and to examine the potential impact on hard clinical endpoints.

The relationship between body mass index and sleep in women with risk factors for gestational diabetes mellitus.

Background: Both obesity and sleep disorders are common among women during pregnancy. Although prior research has identified a relationship between obesity and sleep disorders, those findings are from women later in pregnancy. Objective: To explore the relationships between self-reported sleep duration, insufficient sleep and snoring with body mass index (BMI) among multiethnic women at risk of gestational diabetes mellitus (GDM)in early pregnancy. Methods: Cross-sectional study of baseline data from women at risk of GDM enrolled in the Treatment of BOoking Gestational diabetes Mellitus (TOBOGM) multicentre trial across 12 Australian/Austrian sites. Participants completed a questionnaire before 20 weeks' gestation to evaluate sleep. BMI <25 kg/m2 served as the reference group in multivariable logistic regression. Results: Among the 2865 women included, the prevalence of overweight and obesity classes I-III was 28%, 19%, 11% and 12%, respectively. There was no relationship between sleep duration and BMI. The risk of insufficient sleep >5 days/month was higher in class II and class III obesity (1.38 (1.03-1.85) and 1.34 (1.01-1.80), respectively), and the risk of snoring increased as BMI increased (1.59 (1.25-2.02), 2.68 (2.07-3.48), 4.35 (3.21-5.88) to 4.96 (3.65-6.74), respectively)). Conclusions: Obesity is associated with insufficient sleep among pregnant women at risk of GDM. Snoring is more prevalent with increasing BMI.

Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. METHODS: Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA). RESULTS: A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. CONCLUSIONS: Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.

Gestational Diabetes (GDM) is high blood sugar that develops during pregnancy and may cause complications. GDM diagnosis is centered on blood sugar levels. Despite everyone receiving standard treatment, the clinical outcomes may vary from one individual to another. This indicates a need to identify factors that may help GDM diagnosis and result in improved classification of those at greatest risk for complications. Here, we systematically analyzed all published evidence for potential markers that could identify those with GDM who have greater risk of complications. We find that high maternal weight is a risk factor for offspring born larger for their gestational age. Other promising markers were identified, but further analysis is needed before they can be applied in the clinic.

The effects of canagliflozin in type 2 diabetes in subgroups defined by population-specific body mass index: Insights from the CANVAS Program and CREDENCE trial.

AIM: To assess the effects of canagliflozin on clinical outcomes and intermediate markers across population-specific body mass index (BMI) categories in the CANVAS Program and CREDENCE trial. METHODS: Individual participant data were pooled and analysed in subgroups according to population-specific BMI. The main outcomes of interest were: major adverse cardiovascular events (MACE, a composite of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death); composite renal outcome; and changes in systolic blood pressure (SBP), body weight, albuminuria and estimated glomerular filtration rate (eGFR) slope. Cox proportional hazards models and mixed-effect models were used. RESULTS: A total of 14 520 participants were included, of whom 9378 (65%) had obesity. Overall, canagliflozin reduced the risk of MACE (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.75 to 0.93) with no heterogeneity of treatment effect across BMI subgroups (Pheterogeneity = 0.76). Similarly, canagliflozin reduced composite renal outcomes (HR 0.75, 95% CI 0.66 to 0.84) with no heterogeneity across subgroups observed (Pheterogeneity = 0.72). The effects of canagliflozin on body weight and SBP differed across BMI subgroups (Pheterogeneity <0.01 and 0.04, respectively) but were consistent for albuminuria (Pheterogeneity = 0.60). Chronic eGFR slope with canagliflozin treatment was consistent across subgroups (Pheterogeneity >0.95). CONCLUSIONS: The cardiovascular and renal benefits of canagliflozin and its safety profile were consistent across population-specific BMI subgroups for adults in the CANVAS Program and CREDENCE trial.

Using health administrative data to model associations and predict hospital admissions and length of stay for people with eating disorders.

BACKGROUND: Eating disorders are serious mental illnesses requiring a whole of health approach. Routinely collected health administrative data has clinical utility in describing associations and predicting health outcome measures. This study aims to develop models to assess the clinical utility of health administrative data in adult eating disorder emergency presentations and length of stay. METHODS: Retrospective cohort study on health administrative data in adults with eating disorders from 2014 to 2020 in Sydney Local Health District. Emergency and admitted patient data were collected with all clinically important variables available. Multivariable regression models were analysed to explore associations and to predict admissions and length of stay. RESULTS: Emergency department modelling describes some clinically important associations such as decreased odds of admission for patients with Bulimia Nervosa compared to Anorexia Nervosa (Odds Ratio [OR] 0.31, 95% Confidence Interval [95%CI] 0.10 to 0.95; p = 0.04). Admitted data included more predictors and therefore further significant associations including an average of 0.96 days increase in length of stay for each additional count of diagnosis/comorbidities (95% Confidence Interval [95% CI] 0.37 to 1.55; p = 0.001) with a valid prediction model (R2 = 0.56). CONCLUSIONS: Health administrative data has clinical utility in adult eating disorders with valid exploratory and predictive models describing associations and predicting admissions and length of stay. Utilising health administrative data this way is an efficient process for assessing impacts of multiple factors on patient care and predicting health care outcomes.

Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy.

BACKGROUND: Whether treatment of gestational diabetes before 20 weeks' gestation improves maternal and infant health is unclear. METHODS: We randomly assigned, in a 1:1 ratio, women between 4 weeks' and 19 weeks 6 days' gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the results of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks' gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks' gestation, birth trauma, birth weight of ≥4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass. RESULTS: A total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9%). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, -5.6 percentage points; 95% confidence interval [CI], -10.1 to -1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, -1.6 to 2.9). The mean neonatal lean body mass was 2.86 kg in the immediate-treatment group and 2.91 kg in the control group (adjusted mean difference, -0.04 kg; 95% CI, -0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment. CONCLUSIONS: Immediate treatment of gestational diabetes before 20 weeks' gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.).

Oral glucose tolerance test to diagnose gestational diabetes mellitus: Impact of variations in specimen handling.

To improve birth outcomes, all pregnant women without known diabetes are recommended for an oral glucose tolerance test (OGTT) to screen for hyperglycaemia in pregnancy (diabetes in pregnancy or gestational diabetes mellitus (GDM)). This narrative review presents contemporary approaches to minimise preanalytical glycolysis in OGTT samples with a focus on GDM diagnosis using criteria derived from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The challenges of implementing each approach across a diverse Australian healthcare setting were explored. Many Australian sites currently collect and transport OGTT samples at ambient temperature in sodium fluoride (NaF) tubes which is likely to lead to missed diagnosis of GDM in a significant proportion of cases. Alternative preanalytical solutions should be pragmatic and tailored to individual settings and as close as possible to the preanalytical conditions of the HAPO study for correct interpretation of OGTT results. Rapid centrifugation of barrier tubes to separate plasma could be suitable in urban settings provided time to centrifugation is strictly controlled. Tubes containing NaF and citrate could be useful for remote or resource poor settings with long delays to analysis but the impact on the interpretation of OGTT results should be carefully considered. Testing venous blood glucose at the point-of-care bypasses the need for glycolytic inhibition but requires careful selection of devices with robust analytical performance. Studies to evaluate the potential error of each solution compared to the HAPO protocol are required to assess the magnitude of misdiagnosis and inform clinicians regarding the potential impact on patient safety and healthcare costs.

Maternal and neonatal outcomes of women with gestational diabetes and without specific medical conditions: an Australian population-based study comparing induction of labor with expectant management.

BACKGROUND/AIMS: To evaluate maternal birth and neonatal outcomes among women with gestational diabetes mellitus (GDM), but without specific medical conditions and eligible for vaginal birth who underwent induction of labour (IOL) at term compared with those who were expectantly managed. MATERIALS AND METHODS: Population-based cohort study of women with GDM, but without medical conditions, who had a singleton, cephalic birth at 38-41 completed weeks gestation, in New South Wales, Australia between January 2010 and December 2016. Women who underwent IOL at 38, 39, 40 weeks gestation (38-, 39-, 40-induction groups) were compared with those who were managed expectantly and gave birth at and/or beyond the respective gestational age group (38-, 39-, 40-expectant groups). Multivariable logistic regression analysis was used to assess the association between IOL and adverse maternal birth and neonatal outcomes taking into account potential confounding by maternal age, country of birth, smoking, residential location, residential area of socioeconomic disadvantage and birth year. RESULTS: Of 676 762 women who gave birth during the study period, 66 606 (10%) had GDM; of these, 34799 met the inclusion criteria. Compared with expectant management, those in 38- (adjusted odds ratio (aOR) 1.11; 95% CI, 1.04-1.18), 39- (aOR 1.21; 95% CI, 1.14-1.28) and 40- (aOR 1.50; 95% CI, 1.40-1.60) induction groups had increased risk of caesarean section. Women in the 38-induction group also had an increased risk of composite neonatal morbidity (aOR 1.10; 95% CI, 1.01-1.21), which was not observed at 39- and 40-induction groups. We found no difference between groups in perinatal death or neonatal intensive care unit admission for births at any gestational age. CONCLUSION: In women with GDM but without specific medical conditions and eligible for vaginal birth, IOL at 38, 39, 40 weeks gestation is associated with an increased risk of caesarean section.

A Clinical Update on Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) traditionally refers to abnormal glucose tolerance with onset or first recognition during pregnancy. GDM has long been associated with obstetric and neonatal complications primarily relating to higher infant birthweight and is increasingly recognized as a risk factor for future maternal and offspring cardiometabolic disease. The prevalence of GDM continues to rise internationally due to epidemiological factors including the increase in background rates of obesity in women of reproductive age and rising maternal age and the implementation of the revised International Association of the Diabetes and Pregnancy Study Groups' criteria and diagnostic procedures for GDM. The current lack of international consensus for the diagnosis of GDM reflects its complex historical evolution and pragmatic antenatal resource considerations given GDM is now 1 of the most common complications of pregnancy. Regardless, the contemporary clinical approach to GDM should be informed not only by its short-term complications but also by its longer term prognosis. Recent data demonstrate the effect of early in utero exposure to maternal hyperglycemia, with evidence for fetal overgrowth present prior to the traditional diagnosis of GDM from 24 weeks' gestation, as well as the durable adverse impact of maternal hyperglycemia on child and adolescent metabolism. The major contribution of GDM to the global epidemic of intergenerational cardiometabolic disease highlights the importance of identifying GDM as an early risk factor for type 2 diabetes and cardiovascular disease, broadening the prevailing clinical approach to address longer term maternal and offspring complications following a diagnosis of GDM.

Comparison of a subcutaneous versus intravenous insulin protocol for managing hyperglycemia following antenatal betamethasone in women with diabetes: a pilot randomized controlled trial.

INTRODUCTION: Evaluate the safety and efficacy of a subcutaneous insulin (SC-I) versus intravenous insulin (IV-I) protocol for optimizing maternal blood glucose levels (BGLs) post-betamethasone administration. METHODS: Randomized controlled in-patient pilot study in pregnant women with diabetes, excluding type 1 diabetes, receiving betamethasone ≥24 weeks' gestation. Interventions were stratified SC-I and IV-I protocols, titrated to hourly BGLs (IV-I) or predicted maternal hyperglycemia and 2-4 hourly BGLs (SC-I). Primary outcome was percentage at-target BGL 4.0-8.0 mmol/L over 48 h post-betamethasone. Secondary outcomes were rates of maternal hyperglycemia (>8.0 mmol/L), hypoglycemia (<4.0 mmol/L) and neonatal hypoglycemia (≤2.5 mmol/L). RESULTS: 19 women (3 with type 2 diabetes [T2DM], 4 with gestational diabetes [GDM]-diet, 12 GDM-insulin) were randomized to a SC-I (n = 13) or IV-I (n = 6) protocol in a 9-month period. There was a non-significant trend for higher mean percentage at-target BGLs with SC-I vs IV-I (87% vs 81%; p = .055); this was significant when the cohort was restricted to women with GDM (89% vs 81%; p = .04). Maternal hyperglycemia (85% vs 100%; p = .31) and hypoglycemia (54% vs 33%; p = .41) were not significantly different, but there were no BGLs <3.8 mmol/L with IV-I (vs 4 women with SC-I; p = .13). The rate of neonatal hypoglycemia was not different between groups. CONCLUSION: A SC-I or IV-I protocol controls maternal BGLs following betamethasone, but SC-I appears safe and minimizes labor intensive IV-I in GDM. An adequately powered RCT to assess superiority of SC-I is planned.