The ADIPS pilot national diabetes in pregnancy benchmarking programme

Background: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. Methods: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. Results: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696; type 1 diabetes (T1D) = 435; type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8-57.3%), metformin alone in 18.8% (0.4-43.7%), and metformin and insulin in 10.1% (1.5-23.4%); when compared between sites, all p 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p < 0.001). Conclusion: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy

The Carbohydrate Threshold in Pregnancy and Gestational Diabetes: How Low Can We Go?

The original nutrition approach for the treatment of gestational diabetes mellitus (GDM) was to reduce total carbohydrate intake to 33–40% of total energy (EI) to decrease fetal overgrowth. Conversely, accumulating evidence suggests that higher carbohydrate intakes (60–70% EI, higher quality carbohydrates with low glycemic index/low added sugars) can control maternal glycemia. The Institute of Medicine (IOM) recommends ≥175 g/d of carbohydrate intake during pregnancy; however, many women are consuming lower carbohydrate (LC) diets (&lt;175 g/d of carbohydrate or &lt;40% of EI) within pregnancy and the periconceptual period aiming to improve glycemic control and pregnancy outcomes. This report systematically evaluates recent data (2018–2020) to identify the LC threshold in pregnancy in relation to safety considerations. Evidence from 11 reports suggests an optimal carbohydrate range of 47–70% EI supports normal fetal growth; higher than the conventionally recognized LC threshold. However, inadequate total maternal EI, which independently slows fetal growth was a frequent confounder across studies. Effects of a carbohydrate intake &lt;175 g/d on maternal ketonemia and plasma triglyceride/free fatty acid concentrations remain unclear. A recent randomized controlled trial (RCT) suggests a higher risk for micronutrient deficiency with carbohydrate intake ≤165 g/d in GDM. Well-controlled prospective RCTs comparing LC (&lt;165 g/d) and higher carbohydrate energy-balanced diets in pregnant women are clearly overdue

Risk Management in Gestational Diabetes Mellitus: The Impact of Early Gestational Diabetes Mellitus and the Utility of Early Antenatal Risk Assessment

Gestational diabetes mellitus (GDM), increasing in prevalence, is placing significant demands on limited health resources. In this context, to better target finite resources to those at highest risk we aimed to improve GDM risk stratification approaches and examined whether the timing of GDM diagnosis could infer risk. We found that early GDM (diagnosed before 24 weeks’ gestation) was associated with the highest risk of adverse pregnancy outcomes, despite treatment. Secondly, we explored the utility of a single HbA1c as a pragmatic index of risk at GDM diagnosis. In standard GDM, a threshold HbA1c >5.9% (41 mmol/mol) identified women at increased risk of adverse outcomes and thus baseline HbA1c would have utility as a risk stratification tool at diagnosis. In contrast, HbA1c did not have the same utility in early GDM which should be considered a high-risk cohort. These studies confirm a heterogeneity of risk within GDM and the potential utility of timing of diagnosis and baseline HbA1c as risk stratification tools. The ability in early pregnancy to accurately assess the risk for the development of GDM would allow for limited resources and preventative interventions to be applied in a targeted manner. Thus, we examined the utility of several first trimester multivariate prediction models for GDM. A clinical model achieved an area under the curve (AUC) of 0.88 [95% CI 0.85-0.92], improving on the binary clinical risk scoring systems in current use. The addition of routinely tested first trimester aneuploidy/ pre-eclampsia markers (maternal pregnancy associated plasma protein A, free-β human chorionic gonadotropin, mean arterial pressure and uterine artery pulsatility index), improved prediction and best predicted early GDM (AUC 0.96 [95% CI 0.94-0.98]). Finally, a novel multivariate risk prediction model combining previous markers, glucose, lipids and adipokine biomarkers achieved the highest detection rate for GDM for any given false positive rate of all models tested. Dependent on validation and cost benefit studies, such a model could have potential application to best define a population for GDM preventive strategies or as an alternative to universal screening. Taken together, these findings have important implications for the risk management of GDM

A Practical Approach to Contemporary Obesity Management

One of the basic issues is that health care professionals, and particularly medical graduates, have limited training in obesity care and management. Health care professionals may also have limited awareness of nutrition, physical activity, and behavioral programs to treat obesity and be reluctant to spend time developing and implementing coordinated therapy programs. Obesity management and weight loss maintenance is therefore, a long_term process requiring initial intervention with an ongoing follow_up program. Obesity is usually determined by the measurement of the body mass index, which is the individual's weight in kilograms (kg) divided by their height in meters (m) squared. The impact of COVID-19 on individuals with obesity underlines the urgent requirement for effective policies and strategies for the prevention of overweight and obesity starting in childhood but engaging young and older adults. A treatment program is usually decided upon by an assessment of adiposity and the presence of the complications of obesity

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

Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management

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

Baseline HbA1c to identify high-risk gestational diabetes : utility in early vs standard gestational diabetes

Context: 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. Objective: To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed 5.9% (41mmol/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. Conclusions: Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-forgestational-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

A first trimester prediction model for gestational diabetes utilizing aneuploidy and pre-eclampsia screening markers

Objective: We examined whether first trimester aneuploidy and pre-eclampsia screening markers predict gestational diabetes mellitus (GDM) in a large multi-ethnic cohort and the influence of local population characteristics on markers. Methods: Clinical and first trimester markers (mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI), pregnancy associated plasma protein A (PAPP-A), free-β human chorionic gonadotropin (free-hCGβ)) were measured in a case-control study of 980 women (248 with GDM, 732 controls) at 11 to 13 + 6 weeks’ gestation. Clinical parameters, MAP-, UtA PI-, PAPP-A-, and free-hCGβ-multiples-of-the-median (MoM) were compared between GDM and controls; stratified by ethnicity, parity, and GDM diagnosis <24 versus ≥24 weeks’ gestation. GDM model screening performance was evaluated using AUROC. Results: PAPP-A- and UtA PI-MoM were significantly lower in GDM versus controls (median ((IQR) PAPP-A-MoM 0.81 (0.58–1.20) versus 1.00 (0.70–1.46); UtA PI-MoM 1.01 (0.82–1.21) versus 1.05 (0.84–1.29); p <.05). Previous GDM, family history of diabetes, south/east Asian ethnicity, parity, BMI, MAP, UtA PI, and PAPP-A were significant predictors in multivariate analysis (p <.05). The AUC for a model based on clinical parameters was 0.88 (95%CI 0.85–0.92), increasing to 0.90 (95%CI 0.87–0.92) with first trimester markers combined. The combined model best predicted GDM <24 weeks’ gestation (AUC 0.96 (95%CI 0.94–0.98)). Conclusions: Addition of aneuploidy and pre-eclampsia markers is cost-effective and enhances early GDM detection, accurately identifying early GDM, a high-risk cohort requiring early detection, and intervention. Ethnicity and parity modified marker association with GDM, suggesting differences in pathophysiology and vascular risk