Macroprolactinoma in an adolescent female with primary amenorrhoea.

Summary: Paediatric pituitary adenomas are rare in children and adolescents and differ from adults in both clinical presentation and management. We present the case of a 14-year-old female with primary amenorrhoea secondary to a macroprolactinoma, showing a modest radiological and biochemical response to dopamine agonist (DA) therapy. Despite a 10-month duration of increasing DA therapy, initial symptoms of primary amenorrhoea and hyperprolactinaemia persisted, with new symptoms of weight gain, lethargy and low mood.

Initiating or switching to insulin degludec/insulin aspart in a real-world population of adults with type 2 diabetes in Australia: results from a prospective, non-interventional study.

Background: Insulin degludec/insulin aspart (IDegAsp) is a fixed-ratio co-formulation of insulin degludec and insulin aspart for the treatment of people with diabetes and suboptimal glycaemic control. Few real-world studies of IDegAsp treatment have been conducted. Here, we report results from the Australian cohort of the global ARISE study of real-world IDegAsp use.

Kidney outcomes are altered by preconception weight modulation in rodent mothers with obesity.

Obesity increases the risk of chronic kidney disease. We have previously demonstrated the benefits of preconception maternal weight loss on fertility and pregnancy outcomes in a mouse model of maternal obesity. Here, we elucidate if preconception weight loss, either by diet modification or the glucose-like peptide 1 agonist liraglutide, used in the treatment of diabetes and obesity, improves maternal kidney outcomes in late gestation.

A systematic review of the effects of maternal obesity on neonatal outcomes in women with gestational diabetes.

Maternal obesity and gestational diabetes mellitus (GDM) prevalence are increasing, with both conditions associated with adverse neonatal outcomes. This review aimed to determine the risk of adverse outcomes in women with obesity and GDM, compared with women with obesity alone. A systematic search identified 28 eligible articles.

Maternal Weight Intervention in the Perinatal Period Improves Liver Health in the Offspring of Mothers with Obesity.

Early-life exposure to maternal obesity predisposes offspring to metabolic-associated fatty liver disease (MAFLD). This study aimed to determine if peripartum weight loss, either through dietary intervention or pharmacological intervention, improved adverse liver health outcomes in the offspring of mothers with obesity. C57Bl/6 dams were fed a chow diet or a high-fat diet (HFD) for 8 weeks.

Therapeutic Potential for Beta-3 Adrenoreceptor Agonists in Peripheral Arterial Disease and Diabetic Foot Ulcers.

Annually, peripheral arterial disease is estimated to cost over USD 21 billion and diabetic foot disease an estimated at USD 9-13 billion. Mirabegron is a TGA-approved beta-3 adrenoreceptor agonist, shown to be safe and effective in the treatment of overactive bladder syndrome by stimulating bladder smooth muscle relaxation. In this review, we discuss the potential use of beta-3 adrenoreceptor agonists as therapeutic agents repurposed for peripheral arterial disease and diabetic foot ulcers.

Maternal Weight Management to Prevent the Developmental Programming of MAFLD in Offspring of Obese Mothers.

The global surge of obesity amongst women of reproductive age has raised concerns surrounding the health consequences for their offspring as there is a formidable link between an obesogenic maternal environment and the developmental programming of metabolic dysfunction in the offspring. Specifically, the offspring of mothers with obesity have a three-fold higher risk of developing metabolic-associated fatty liver disease (MAFLD) compared to the offspring of healthy-weight mothers. Given the burgeoning burden of obesity and its comorbidities, it is essential to focus research efforts on methods to alleviate the intergenerational onset of obesity and MAFLD.

Fasting Glucose Level on the Oral Glucose Tolerance Test Is Associated with the Need for Pharmacotherapy in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) has a rapidly increasing prevalence, which poses challenges to obstetric care and service provision, with known serious long-term impacts on the metabolic health of the mother and the affected offspring. The aim of this study was to evaluate the association between glucose levels on the 75 g oral glucose tolerance test and GDM treatment and outcomes. We performed a retrospective cohort study of women with GDM attending a tertiary Australian hospital obstetric clinic between 2013 and 2017, investigating the relationship between the 75 g oral glucose tolerance test (OGTT) glucose values, and obstetric (timing of delivery, caesarean section, preterm birth, preeclampsia), and neonatal (hypoglycaemia, jaundice, respiratory distress and NICU admission) outcomes.

A case series and literature review of necrobiosis lipoidica.

Summary: Necrobiosis lipoidica (NL) is a rare and chronic disease characterised by yellow-brown, atrophic, telangiectatic plaques usually located on the lower extremities, with pathological features of collagen necrobiosis and dermal inflammation. Most cases are seen in those with diabetes mellitus, particularly type 1 diabetes (T1DM), and many without diabetes have evidence of abnormal glucose tolerance or family history of autoimmune disease. In this study, we describe four patients with NL and T1DM.

Low-dose hydralazine reduces albuminuria and glomerulosclerosis in a mouse model of obesity-related chronic kidney disease.

Aim: To determine, using a mouse model of obesity, whether low-dose hydralazine prevents obesity-related chronic kidney disease (CKD).

Methods: From 8 weeks of age, male C57BL/6 mice received a high-fat diet (HFD) or chow, with or without low-dose hydralazine (25 mg/L) in drinking water, for 24 weeks. Biometric and metabolic variables, renal function and structural changes, renal global DNA methylation, DNA methylation profile and markers of renal fibrosis, injury, inflammation and oxidative stress were assessed.

Diet Modification before or during Pregnancy on Maternal and Foetal Outcomes in Rodent Models of Maternal Obesity.

The obesity epidemic has serious implications for women of reproductive age; its rising incidence is associated not just with health implications for the mother but also has transgenerational ramifications for the offspring. Increased incidence of diabetes, cardiovascular disease, obesity, and kidney disease are seen in both the mothers and the offspring. Animal models, such as rodent studies, are fundamental to studying maternal obesity and its impact on maternal and offspring health, as human studies lack rigorous controlled experimental design.

Obesity Class Impacts Adverse Maternal and Neonatal Outcomes Independent of Diabetes.

Introduction: Obesity in pregnancy is a known risk factor for adverse maternal and neonatal outcomes. Few studies have compared adverse pregnancy-related outcomes according to obesity severity. Hence, we aimed to examine the impact of obesity class on maternal and perinatal outcomes.

Preconception weight loss improves fertility and maternal outcomes in obese mice.

Women with obesity have higher incidences of infertility, with longer time to conception and increased risk of pregnancy complications compared to women with normal body weight. There is a lack of evidence demonstrating the benefit of preconception maternal weight loss on fertility and pregnancy outcomes. We aimed to determine if preconception weight loss, either with diet modification or glucose-like peptide 1 receptor agonist liraglutide, improves maternal weight, fertility, and pregnancy outcomes.

The Role of the Gut Microbiome in Diabetes and Obesity-Related Kidney Disease.

Diabetic kidney disease (DKD) is a progressive disorder, which is increasing globally in prevalence due to the increased incidence of obesity and diabetes mellitus. Despite optimal clinical management, a significant number of patients with diabetes develop DKD. Hence, hitherto unrecognized factors are likely to be involved in the initiation and progression of DKD.

Novel Role of Gestational Hydralazine in Limiting Maternal and Dietary Obesity-Related Chronic Kidney Disease.

Background: Maternal obesity is a risk factor for chronic kidney disease (CKD) in offspring, underpinning the theory of the developmental origins of health and disease. DNA methylation has been implicated in the programming of adult chronic disease by maternal obesity, therefore, DNA demethylating agents may mitigate offspring risk of disease. In rodent models, low-dose hydralazine has previously been shown to reduce renal fibrosis via DNA demethylation.

Are newly introduced criteria for the diagnosis of gestational diabetes mellitus associated with improved pregnancy outcomes and/or increased interventions in New South Wales, Australia? A population-based data linkage study.

Introduction: The incidence of gestational diabetes mellitus (GDM) is increasing in Australia, influenced by changed diagnostic criteria. We aimed to identify whether the diagnostic change was associated with improved outcomes and/or increased obstetric interventions using state-wide data in New South Wales (NSW), Australia.

Research Design And Methods: Perinatal and hospital data were linked for singleton births, 33-41 weeks' gestation, 2006-2015, NSW.

Complexities surrounding the diagnosis and management of hypercalcaemia in pregnancy.

Summary: Hypercalcaemia in pregnancy is uncommon, with associated adverse obstetric and perinatal outcomes for both the mother and the fetus. Determination of causality is central to its management. Diagnostic imaging techniques are limited during pregnancy and the diagnosis is made more complex by physiological changes in calcium and vitamin D homeostasis in pregnancy.

Low-dose hydralazine during gestation reduces renal fibrosis in rodent offspring exposed to maternal high fat diet.

Background: Maternal high fat diet (HFD) promotes chronic kidney disease (CKD) in offspring. This is in accordance with the theory of fetal programming, which suggests adverse conditions occurring in utero predispose offspring to chronic conditions later in life. DNA methylation has been proposed as a key mechanism by which fetal programming occurs and is implicated in CKD progression.

The Clinical Role of Insulin Degludec/Insulin Aspart in Type 2 Diabetes: An Empirical Perspective from Experience in Australia.

Treatment intensification in people with type 2 diabetes following failure of basal insulin commonly involves the addition of a rapid-acting insulin analogue (basal plus one or more prandial doses; multiple daily injections) or by a switch to premixed insulin. Insulin degludec/insulin aspart (IDegAsp), comprising rapid-acting insulin aspart and ultra-long-acting insulin degludec in solution, enables both fasting and post-prandial glucose control, with some advantages over other treatment intensification options. These include straightforward dose titration, flexibility in dose timing, low injection burden, simplicity of switching and a lower risk of hypoglycaemia.

Large-for-Gestational-Age Neonates in Type 1 Diabetes and Pregnancy: Contribution of Factors Beyond Hyperglycemia.

Despite significant reductions in serious adverse perinatal outcomes for women with type 1 diabetes in pregnancy, the opposite effect has been observed for fetal overgrowth and associated complications, such as neonatal hypoglycemia, shoulder dystocia, and admission to the neonatal intensive care unit. In addition, infants born large for gestational age (LGA) have an increased lifetime risk of obesity, diabetes, and chronic disease. Although exposure to hyperglycemia plays an important role, women who seemingly achieve adequate glycemic control in pregnancy continue to experience a greater risk of excess fetal growth, leading to LGA neonates and macrosomia.

The Emerging Role of Biomarkers in the Diagnosis of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy; its rising incidence is a result of increased maternal obesity and older maternal age together with altered diagnostic criteria identifying a greater proportion of pregnant women with GDM. Its consequences are far-reaching, associated with poorer maternal and neonatal outcomes compared to non-GDM pregnancies, and GDM has implications for metabolic health in both mother and offspring. Objective markers to identify women at high risk for the development of GDM are useful to target therapy and potentially prevent its development.

DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.

Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD.