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Abstract 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. Graphical Abstract Graphical Abstract

Treatment of gestational diabetes before 20 weeks’ gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes but no material differences in pregnancy-related hypertension or neonatal lean body mass.

The increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes. To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed <24 vs ≥24 weeks' gestation (early vs standard GDM). This was a retrospective cohort study undertaken at the Royal Prince Alfred Hospital Diabetes Antenatal Clinic, Australia, between 1991 and 2011. Pregnant women (N = 3098) underwent an HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively. The association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM. HbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia. Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort.

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 (R 2  = 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.

The US Food and Drug Administration (FDA) recently approved lorcaserin and the combination of phentermine and extended release topiramate (phentermine/topiramate ER) for the treatment of obesity in conjunction with a lifestyle intervention, expanding the therapeutic options for long-term obesity pharmacotherapy, which was previously limited to orlistat. Combination phentermine/topiramate ER is associated with greater weight loss compared to its constituent monotherapy, with a more favorable adverse effect profile. Phentermine/topiramate ER also appears to have beneficial effects on cardiometabolic risk, although longer-term cardiovascular safety data are required. While there are no head-to-head studies among the currently available obesity pharmacotherapy agents, phentermine/topiramate ER appears to have a superior weight loss profile. This review will discuss the epidemiology, natural history, and cardiometabolic risk associated with obesity, provide an overview on current obesity pharmacotherapy, and summarize the recent clinical efficacy and safety data underpinning the FDA's approval of both phentermine/topiramate ER and lorcaserin as pharmacotherapy for a long-term obesity intervention.

Current research around effective recruitment strategies for clinical trials of dietary obesity treatments have largely focused on younger adults, and thus may not be applicable to older populations. The TEMPO Diet Trial (Type of Energy Manipulation for Promoting optimal metabolic health and body composition in Obesity) is a randomised controlled trial comparing the long-term effects of fast versus slow weight loss on body composition and cardio-metabolic health in postmenopausal women with obesity. This paper addresses the recruitment strategies used to enrol participants into this trial and evaluates their relative effectiveness. 101 post-menopausal women aged 45–65 years, with a body mass index of 30–40 kg/m2 were recruited and randomised to either fast or slow weight loss. Multiple strategies were used to recruit participants. The total time cost (labour) and monetary cost per randomised participant from each recruitment strategy was estimated, with lower values indicating greater cost-effectiveness and higher values indicating poorer cost-effectiveness. The most cost-effective recruitment strategy was word of mouth, followed (at equal second place) by free publicity on TV and radio, and printed advertorials, albeit these avenues only yielded 26/101 participants. Intermediate cost-effective recruitment strategies were flyer distribution at community events, hospitals and a local tertiary education campus, internet-based strategies, and clinical trial databases and intranets, which recruited a further 40/101 participants. The least cost-effective recruitment strategy was flyer distribution to local health service centres and residential mailboxes, and referrals from healthcare professionals were not effective. Recruiting for clinical trials involving postmenopausal women could benefit from a combination of recruitment strategies, with an emphasis on word of mouth and free publicity via radio, TV, and print media, as well as strategic placement of flyers, supplemented with internet-based strategies, databases and intranets if a greater yield of participants is needed.

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.

Immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) are a standard of care for advanced melanoma. Novel toxicities comprise immune-related adverse events (irAE). With increasing use, irAE require recognition, practical management strategies, and multidisciplinary care. We retrospectively evaluated the incidence, kinetics, and management of irAE in 41 patients receiving anti-PD-1 antibody therapy (pembrolizumab) for advanced melanoma. 63% received prior anti-CTLA-4 antibody therapy (ipilimumab). IrAE occurred in 54%, most commonly dermatological (24%), rheumatological (22%), and thyroid dysfunction (12%). Thyroiditis was characterised by a brief asymptomatic hyperthyroid phase followed by a symptomatic hypothyroid phase requiring thyroxine replacement. Transplant rejection doses of methylprednisolone were necessary to manage refractory hepatotoxicity. A bullous pemphigoid-like skin reaction with refractory pruritus responded to corticosteroids and neuropathic analgesia. Disabling grade 3-4 oligoarthritis required sulfasalazine therapy in combination with steroids. The median interval between the last dose of anti-CTLA-4 antibody and the first dose of anti-PD-1 therapy was 2.0 months (range: 0.4 to 22.4). Toxicities may occur late; this requires vigilance and multidisciplinary management which may allow effective anticancer therapy to continue. Management algorithms for thyroiditis, hypophysitis, arthralgia/arthritis, colitis, steroid-refractory hepatitis, and skin toxicity are discussed.

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.

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.