ORCID Profile
0000-0002-9317-1348
Current Organisations
Northern Sydney Endocrine Centre
,
North Shore Private Hospital
,
University of Sydney
,
Royal North Shore Hospital
,
Royal College of Physicians
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Publisher: Bioscientifica
Date: 04-2022
DOI: 10.1530/JOE-21-0399
Abstract: 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. C57BL/6 female mice were fed either a high-fat diet (HFD) or chow for 8 weeks. HFD-fed dams were administered liraglutide (0.3 mg/kg, s.c., for 4 weeks) or switched to chow to induce weight loss. Prior to mating, liraglutide was ceased and mice continued on HFD. Mice in the ‘diet switch’ group continued on chow. Pregnancy rates were recorded. Maternal anthropometry and glucose tolerance were measured before and after the intervention and at late gestation. Offspring outcomes were assessed. Liraglutide or diet switch led to weight reduction, improved insulin resistance ( P 0.001), and enhanced fertility, particularly in the liraglutide group ( P 0.005). Liraglutide-treated mice had significantly higher gestational weight gain (GWG) compared to the diet switch group ( P 0.05), with similar weight and glucose tolerance in late gestation to HFD mice. In contrast, diet switch maintained similar weight and glucose tolerance in late gestation to control mice. Pre-pregnancy weight intervention with liraglutide was effective at restoring fertility. Diet modification also improved fertility and avoided catch up weight gain in pregnancy. Liraglutide may be a therapeutic strategy for weight loss to prepare for pregnancy. However, our study provides caution about the potential for excessive GWG without diet intervention in pregnancy.
Publisher: Springer Science and Business Media LLC
Date: 23-03-2016
DOI: 10.1038/SREP23525
Abstract: Maternal obesity is associated with an increased risk of chronic disease in offspring, including type 2 diabetes (T2D). Exendin-4 (Exd-4) activates the glucagon like peptide-1 (GLP-1) receptor thereby decreasing serum glucose levels and body weight. In addition, Exd-4 has been shown to reduce renal and cardiac complications in experimental models of T2D. We hypothesized that treatment with Exd-4 would ameliorate the detrimental effects of maternal and diet-induced obesity on renal characteristics in offspring. Female Sprague-Dawley rats were fed either normal or high-fat diet (HFD) for 6 weeks prior to pregnancy, during pregnancy and lactation, and their offspring were weaned to normal or HFD. The offspring were randomized to Exd-4 or placebo from weaning and their kidneys harvested at Week 9. We found that the kidneys of offspring from obese mothers, regardless of postnatal diet, had significantly increased markers of inflammation, oxidative stress and fibrosis. Exd-4 ameliorated the negative renal effects of maternal obesity and in particular, reduced renal inflammation, oxidative stress and fibrosis. In conclusion, maternal obesity has persisting effects on renal structure in the offspring. GLP-1 analogues are potentially useful for protecting against the deleterious effects of maternal obesity on renal physiology in offspring.
Publisher: Frontiers Media SA
Date: 21-10-2021
Publisher: Elsevier BV
Date: 10-2018
Publisher: Frontiers Media SA
Date: 18-08-2021
DOI: 10.3389/FCELL.2021.705263
Abstract: 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. We used mouse models of maternal obesity and offspring obesity to determine whether administration of low-dose hydralazine during gestation can prevent fetal programming of CKD in offspring. Female C57BL/6 mice received high fat diet (HFD) or chow prior to mating, during gestation and lactation. During gestation, dams received subcutaneous hydralazine (5 mg/kg) or saline thrice-weekly. Male offspring weaned to HFD or chow, which continued until endpoint at 32 weeks. Biometric and metabolic parameters, renal global DNA methylation, renal functional and structural changes, and renal markers of fibrosis, inflammation and oxidative stress were assessed at endpoint. Offspring exposed to maternal obesity or diet-induced obesity had significantly increased renal global DNA methylation, together with other adverse renal effects including albuminuria, glomerulosclerosis, renal fibrosis, and oxidative stress. Offspring exposed to gestational hydralazine had significantly reduced renal global DNA methylation. In obese offspring of obese mothers, gestational hydralazine significantly decreased albuminuria, glomerulosclerosis, and serum creatinine. Obese offspring of hydralazine-treated lean mothers displayed reduced markers of renal fibrosis and oxidative stress. Gestational hydralazine decreased renal global DNA methylation and exerted renoprotective effects in offspring. This supports a potential therapeutic effect of hydralazine in preventing maternal obesity or dietary obesity-related CKD, through an epigenetic mechanism.
Publisher: MDPI AG
Date: 30-04-2023
DOI: 10.3390/NU15092155
Abstract: 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. This review summarizes the current research surrounding the developmental programming of MAFLD in the offspring of mothers with obesity and examines the potential for weight interventions to prevent such metabolic dysfunction in the offspring. It focuses on the benefits of pre-pregnancy interventional strategies, including dietary and exercise intervention, to ameliorate adverse liver health outcomes in the offspring. The utility and translation of these interventions for humans may be difficult for prospective mothers with obesity, thus the use of pre-pregnancy therapeutic weight loss aids, such as glucagon-like peptide-1 receptor agonists, is also discussed.
Publisher: Elsevier BV
Date: 03-2016
Publisher: European Medical Group
Date: 25-05-2020
Abstract: Gestational diabetes mellitus (GDM) is a frequent complication of pregnancy, with an increasing incidence that has been attributed to an ageing maternal population, an increasing prevalence of obesity, and alterations in diagnostic criteria. The consequences of GDM are far-reaching and impact both the mother and their offspring. It is associated with poor maternal and neonatal outcomes compared with non-GDM pregnancies. Furthermore, it is associated with long-term poor metabolic health in both mother and offspring. Current diagnostic strategies centre on clinical risk factors, however these can lack specificity. This has spurred investigations into identifying potential biomarkers to aid in diagnosis and risk stratification. In this review, the current evidence around potential biomarkers, their role in understanding pathophysiologic pathways for GDM development, and the possibility of their use in clinical practice is explored.
Publisher: Public Library of Science (PLoS)
Date: 31-08-2016
Publisher: American Physical Society (APS)
Date: 28-06-2017
Publisher: Wiley
Date: 10-2008
Publisher: Public Library of Science (PLoS)
Date: 18-03-2021
DOI: 10.1371/JOURNAL.PONE.0248854
Abstract: 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. DNA demethylating drugs may interrupt the fetal programming of CKD by maternal obesity. Hydralazine, an antihypertensive agent, demethylates DNA at low doses which do not reduce blood pressure. We used a mouse model of maternal obesity to determine whether gestational administration of low-dose hydralazine to mothers can prevent CKD in offspring. C57BL/6 dams received HFD or chow from 6 weeks prior to mating and were administered subcutaneous hydralazine (5mg/kg) or saline thrice weekly during gestation. Male offspring were weaned to chow and were sacrificed at either postnatal week 9 or week 32. Biometric and metabolic parameters, renal global DNA methylation, renal structural and functional changes and markers of fibrosis, oxidative stress and inflammation were measured in offspring at weeks 9 and 32. In week 9 offspring, maternal HFD consumption did not significantly alter anthropometric or metabolic parameters, or renal global DNA methylation. Week 32 offspring had increased renal global DNA methylation, together with albuminuria, glomerulosclerosis, renal fibrosis and oxidative stress. Administration of low-dose hydralazine to obese mothers during gestation reduced renal global DNA methylation and renal fibrotic markers in week 32 offspring. Gestational hydralazine reduced renal global DNA methylation in offspring of obese mothers and attenuated maternal obesity-induced renal fibrosis. These data support the use of low-dose hydralazine as a demethylating agent to prevent CKD arising in offspring due to maternal HFD consumption.
Publisher: Springer Science and Business Media LLC
Date: 12-2016
DOI: 10.1186/S12933-016-0481-7
Abstract: Diastolic dysfunction is a major cause of morbidity in obese in iduals. We aimed to assess the ability of magnetic resonance imaging (MRI) derived left atrial (LA) strain to detect early diastolic dysfunction in in iduals with obesity and type 2 diabetes, and to explore the association between cardiac adipose tissue and LA function. Twenty patients with obesity and T2D (55 ± 8 years) and nineteen healthy controls (48 ± 13 years) were imaged using cine steady state free precession and 2-point Dixon cardiovascular magnetic resonance. LA function was quantified using a feature tracking technique with definition of phasic longitudinal strain and strain rates, as well as radial motion fraction and radial velocities. Systolic left ventricular size and function were similar between the obesity and type 2 diabetes and control groups by MRI. All patients except four had normal diastolic assessment by echocardiography. In contrast, measures of LA function using magnetic resonance feature tracking were uniformly altered in the obesity and type 2 diabetes group only. Although there was no significant difference in intra-myocardial fat fraction, Dixon 3D epicardial fat volume(EFV) was significantly elevated in the obesity and type 2 diabetes versus control group (135 ± 31 vs. 90 ± 30 mL/m 2 , p 0.001). There were significant correlations between LA functional indices and both BMI and EFV (p ≤ 0.007). LA MRI-strain may be a sensitive tool for the detection of early diastolic dysfunction in in iduals with obesity and type 2 diabetes and correlated with BMI and epicardial fat supporting a possible association between adiposity and LA strain. Trials Registration Australian New Zealand Clinical Trials Registry No. ACTRN12613001069741
Publisher: OMICS Publishing Group
Date: 03-2012
DOI: 10.2217/CPR.12.9
Publisher: American Diabetes Association
Date: 09-2005
DOI: 10.2337/DIACARE.28.9.2170
Abstract: OBJECTIVE—The purpose of this study was to explore whether the presence of thyroid and endomysial autoantibodies at diagnosis of type 1 diabetes in children predicts development of thyroid and celiac disease, respectively, and whether diabetes-associated autoantibodies at diagnosis predict development of microvascular complications up to 13 years later. RESEARCH DESIGN AND METHODS—Autoantibodies were measured at diagnosis of type 1 diabetes in 173 children aged 0–15 years and included thyroperoxidase antibody (TPOA), endomysial antibody (EMA), islet cell autoantibody, GAD antibody (GADA), and insulin autoantibody. Thyroid disease was defined as thyroid stimulating hormone level ≥5 μU/ml. Celiac disease was confirmed by small-bowel biopsy. Assessment of microvascular complications included stereoscopic fundal photography, pupillometry, thermal threshold, and albumin excretion rate (AER). RESULTS—The incidence rates for thyroid and celiac disease were 0.9 and 0.7 per 100 patient-years, respectively. Within 13 years, 6 of 13 children with positive TPOA tests at diagnosis developed thyroid disease compared with 5 of 139 children with negative TPOA tests (P & 0.001). All four patients with positive EMA titers at diagnosis had biopsy-proven celiac disease. Five of 11 patients who developed thyroid disease and 4 of 8 who developed celiac disease had negative TPOA and EMA tests at diagnosis, respectively. Retinopathy was detected in 39% and elevated AER in 36%. The presence of diabetes-associated autoantibodies at diagnosis did not predict microvascular complications though GADA titer levels predicted pupillary abnormality. CONCLUSIONS—Elevated TPOA and EMA levels at diagnosis of type 1 diabetes predict the development of thyroid and celiac disease, respectively. In children with negative antibody titers at diagnosis, screening at 2-year intervals is recommended.
Publisher: Public Library of Science (PLoS)
Date: 22-02-2017
Publisher: Mary Ann Liebert Inc
Date: 02-2016
Abstract: The optimal treatment of diabetes in pregnancy requires accurate measurement of blood glucose levels, in order to minimize adverse outcomes for both mother and neonate. Self-monitoring of blood glucose is routinely used to measure glycemic control and to assess whether treatment targets are being met however, the accuracy of blood glucose meters in pregnancy is unclear. Pregnant women with gestational, type 1, or type 2 diabetes mellitus were eligible to participate. Nonfasting capillary blood glucose levels were measured in duplicate using the BGStar(®) (Sanofi, Sydney, Australia) and FreeStyle Lite(®) (Abbott, Sydney) blood glucose meters. Venous blood s les were collected and analyzed for plasma glucose, hematocrit, and glycated hemoglobin. Capillary blood glucose was compared with plasma glucose and further assessed according to International Organization for Standardization (ISO) 15197:2013 standards. One hundred ten women were recruited, providing 96 s les suitable for analysis. The mean ± SD laboratory plasma glucose level was 4.6 ± 1.4 mmol/L the BGStar and FreeStyle Lite capillary blood glucose values were 5.3 ± 1.4 mmol/L and 5.0 ± 1.3 mmol/L, respectively. Both meters showed a positive bias (0.42 mmol/L for the FreeStyle Lite and 0.65 mmol/L for the BGStar). Furthermore, neither meter fulfilled the ISO 15197:2013 standards, and there was a nonsignificant improvement in meter performance at blood glucose levels of ≤4.2 mmol/L. Hematocrit did not affect the results of either blood glucose meter. Clarke Error Grid analysis demonstrated that approximately 70% of the results of both meters would lead to appropriate clinical action. The BGStar and FreeStyle Lite blood glucose meters did not meet ISO 15197:2013 recommendations for blood glucose monitoring systems when assessed in a population of women with diabetes in pregnancy. Clinicians should consider this difference in blood glucose readings when making diabetes-related treatment decisions.
Publisher: MDPI AG
Date: 06-09-2021
DOI: 10.3390/IJMS22179641
Abstract: 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. An extensive number of studies have demonstrated the role of microbiota in health and disease. Dysregulation in the microbiota resulting in a deficiency of short chain fatty acids (SCFAs) such as propionate, acetate, and butyrate, by-products of healthy gut microbiota metabolism, have been demonstrated in obesity, type 1 and type 2 diabetes. However, it is not clear to date whether such changes in the microbiota are causative or merely associated with the diseases. It is also not clear which microbiota have protective effects on humans. Few studies have investigated the centrality of reduced SCFA in DKD development and progression or the potential therapeutic effects of supplemental SCFAs on insulin resistance, inflammation, and metabolic changes. SCFA receptors are expressed in the kidneys, and emerging data have demonstrated that intestinal dysbiosis activates the renal renin-angiotensin system, which contributes to the development of DKD. In this review, we will summarize the complex relationship between the gut microbiota and the kidney, examine the evidence for the role of gut dysbiosis in diabetes and obesity-related kidney disease, and explore the mechanisms involved. In addition, we will describe the role of potential therapies that modulate the gut microbiota to prevent or reduce kidney disease progression.
Publisher: Elsevier BV
Date: 12-2005
DOI: 10.1016/J.PCL.2005.07.007
Abstract: Complications of diabetes include retinopathy, nephropathy, neuropathy, macrovascular disease, and associated autoimmune diseases. Clinical manifestations of complications uncommonly present in childhood and adolescence. Screening during the early years can identify subclinical disease and it offers an opportunity for early intervention. The Diabetes and Complications Control Trial has provided evidence for the long-term benefits of good glycemic control in preventing and delaying the onset of microvascular complications. Complications begin to manifest during adolescence, during which time all efforts should be made to educate and support young persons in achieving optimal diabetes control.
Publisher: MDPI AG
Date: 09-03-2018
DOI: 10.3390/JCM7030050
Publisher: MDPI AG
Date: 21-05-2022
DOI: 10.3390/NU14102154
Abstract: 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. Furthermore, the short and prolific reproductive potential of rodents enables examination across multiple generations and facilitates the exploration of interventional strategies to mitigate the impact of maternal obesity, both before and during pregnancy. Given that obesity is a major public health concern, it is important to obtain a greater understanding of its pathophysiology and interaction with reproductive health, placental physiology, and foetal development. This narrative review focuses on the known effects of maternal obesity on the mother and the offspring, and the benefits of interventional strategies, including dietary intervention, before or during pregnancy on maternal and foetal outcomes. It further examines the contribution of rodent models of maternal obesity to elucidating pathophysiological pathways of disease development, as well as methods to reduce the impact of obesity on the mothers and the developing foetus. The translation of these findings into the human experience will also be discussed.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.DIABRES.2016.04.051
Abstract: The use of metformin in gestational diabetes is safe and effective, yet some women require additional insulin therapy to achieve glycaemic targets. We found a significant association between earlier gestational age at initiation of metformin therapy and the necessity for supplemental insulin in women treated with metformin during pregnancy.
Publisher: Wiley
Date: 10-2018
DOI: 10.1111/IMJ.13824
Abstract: Prevention of hospitalisation is an important aspect of type 2 diabetes (T2D) management. We retrospectively determined the utility of the Hospital Admission Risk Programme (HARP) diabetes risk calculator (HARP tool) in identifying patients with T2D more likely to have unplanned hospital presentations. The HARP tool includes a clinical assessment score (Part A) and a psychosocial and self-management impact score (Part B), and categorises patients into low, medium, high or urgent risk of acute hospitalisation. It was completed for T2D patients attending Royal North Shore Hospital, Sydney, in 2013. Within the cohort of 278 patients (age 65.3 ± 10.5 years 62.9% male diabetes duration 10.7 ± 6.6 years), 67.3% were classified as low risk, 32.7% as medium risk and none as high or urgent risk. Following adjustment for confounders, a medium HARP score was associated with a 3.1-fold increased risk of unplanned hospital presentations in the subsequent 12 months (95% confidence interval: 1.35-7.31 P = 0.008). Part A scores were significantly higher for patients that presented to hospital compared to those that did not (14.2 ± 6.8 vs 11.4 ± 5.5 P = 0.034), whereas there was no difference in Part B scores (P = 0.860). In patients with low and medium HARP scores, clinical features were more predictive of hospital presentations than certain psychosocial or self-management factors in the present cohort. Further studies are required to characterise unplanned hospitalisation in patients with higher HARP scores, or whether additional psychosocial assessments could improve the tool's predictability.
Publisher: American Diabetes Association
Date: 12-03-2018
DOI: 10.2337/DC17-2594
Publisher: Springer Science and Business Media LLC
Date: 09-06-2016
DOI: 10.1038/SREP27769
Abstract: Maternal obesity is known to increase the risk of obesity and diabetes in offspring. Though diabetes is a key risk factor for the development of chronic kidney disease (CKD), the relationship between maternal obesity and CKD has not been clearly defined. In this study, a mouse model of maternal obesity was employed to determine the impact of maternal obesity on development of diabetic nephropathy in offspring. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow diet. At postnatal Week 8, offspring were randomly administered low dose streptozotocin (STZ, 55 mg/kg/day for five days) to induce diabetes. Assessment of renal damage took place at postnatal Week 32. We found that offspring of obese mothers had increased renal fibrosis, inflammation and oxidative stress. Importantly, offspring exposed to maternal obesity had increased susceptibility to renal damage when an additional insult, such as STZ-induced diabetes, was imposed. Specifically, renal inflammation and oxidative stress induced by diabetes was augmented by maternal obesity. Our findings suggest that developmental programming induced by maternal obesity has implications for renal health in offspring. Maternal obesity should be considered a risk factor for CKD.
Publisher: MDPI AG
Date: 11-04-2020
DOI: 10.3390/JCM9041091
Abstract: 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. In Australia, where insulin degludec on its own is not available, IDegAsp enables patients to still benefit from its ultra-long-acting properties. This review aims to provide guidance on where and how to use IDegAsp. Specifically, guidance is included on the initiation of IDegAsp in insulin-naïve patients, treatment intensification from basal insulin, switching from premixed or basal-bolus insulin to IDegAsp, up-titration from once- to twice-daily IDegAsp and the use of IDegAsp in special populations or situations.
Publisher: Wiley
Date: 23-04-2018
DOI: 10.1111/COB.12249
Abstract: We aimed to describe the current state of specialist obesity services for adults with clinically severe obesity in public hospitals in Australia, and to analyse the gap in resources based on expert consensus. We conducted two surveys to collect information about current and required specialist obesity services and resources using open-ended questionnaires. Organizational level data were sought from clinician expert representatives of specialist obesity services across Australia in 2017. Fifteen of 16 representatives of current services in New South Wales (n = 8), Queensland (n = 1), Victoria (n = 2), South Australia (n = 3), and the Australian Capital Territory (n = 1) provided data. The composition of services varied substantially between hospitals, and patient access to services and effective treatments were limited by strict entry criteria (e.g. body mass index 40 kg/m
Publisher: Wiley
Date: 10-2018
DOI: 10.1111/NEP.13462
Abstract: It is increasingly recognized that maternal obesity is implicated in developmental programming, contributing to the future risk of chronic disease development in offspring. The exact mechanisms of the role of maternal obesity in the development of chronic kidney disease in offspring remain unclear and animal models used are not without limitation. Human studies are limited by the effects of postnatal environmental conditions, which may have a direct impact on disease phenotype and animal models are limited by use of species that differ significantly. This review will examine the most recent evidence from animal models on the impact of maternal factors during pregnancy/lactation on the future risk of chronic kidney disease development in offspring, emphasising the role of maternal obesity in exacerbating the deleterious effects of diet-induced obesity and/or diabetes on renal health.
Publisher: American Diabetes Association
Date: 06-12-2022
DOI: 10.2337/DC21-1666
Abstract: Continuous glucose monitoring (CGM) is increasingly used in type 1 diabetes management however, funding models vary. This study determined the uptake rate and glycemic outcomes following a change in national health policy to introduce universal subsidized CGM funding for people with type 1 diabetes aged & years. Longitudinal data from 12 months before the subsidy until 24 months after were analyzed. Measures and outcomes included age, diabetes duration, HbA1c, episodes of diabetic ketoacidosis and severe hypoglycemia, insulin regimen, CGM uptake, and percentage CGM use. Two data sources were used: the Australasian Diabetes Database Network (ADDN) registry (a prospective diabetes database) and the National Diabetes Service Scheme (NDSS) registry that includes almost all in iduals with type 1 diabetes nationally. CGM uptake increased from 5% presubsidy to 79% after 2 years. After CGM introduction, the odds ratio (OR) of achieving the HbA1c target of & .0% improved at 12 months (OR 2.5, P & 0.001) and was maintained at 24 months (OR 2.3, P & 0.001). The OR for suboptimal glycemic control (HbA1c ≥9.0%) decreased to 0.34 (P & 0.001) at 24 months. Of CGM users, 65% used CGM & % of time, and had a lower HbA1c at 24 months compared with those with usage & % (7.8 ± 1.3% vs. 8.6 ± 1.8%, respectively, P & 0.001). Diabetic ketoacidosis was also reduced in this group (incidence rate ratio 0.49, 95% CI 0.33–0.74, P & 0.001). Following the national subsidy, CGM use was high and associated with sustained improvement in glycemic control. This information will inform economic analyses and future policy and serve as a model of evaluation diabetes technologies.
Publisher: Wiley
Date: 04-05-2023
DOI: 10.1002/EDM2.421
Abstract: Gestational diabetes mellitus (GDM) is experienced at a higher rate in women from culturally and linguistically erse (CALD) backgrounds. The aim of this systematic review is to describe the experiences of women with GDM from CALD backgrounds and compare their experiences to women with GDM from non‐CALD backgrounds. MEDLINE, EMBASE, PsycINFO, Scopus, WOS and CINAHL databases were searched for qualitative and quantitative studies which included data on the experiences of CALD background women with GDM during all stages of pregnancy. Quality appraisal utilized checklists for analytical cross‐sectional studies and qualitative research. Thematic analysis was performed using nVivo software. Of the 3054 studies identified, 24 studies met the inclusion criteria. Data synthesis produced five key themes: (1) Response to diagnosis, (2) Experiences with self‐management, (3) Interactions with the healthcare system, (4) Mental health challenges and (5) Facilitators and barriers to support. Women with GDM from CALD and non‐CALD backgrounds similarly expressed mental health challenges, feeling burdened by recommendations, and challenges interacting with healthcare professionals (HCP). The major difference in experience was the cultural relevance of recommendations, especially related to diet recommendations. Gestational diabetes mellitus is a burdensome diagnosis for CALD and non‐CALD women, with CALD women uniquely experiencing a lack of culturally relevant recommendations for self‐management. The similarities and differences in experience call for optimisation of GDM management and support for women with GDM.
Publisher: Wiley
Date: 16-11-2020
DOI: 10.1111/AJO.13265
Publisher: American Diabetes Association
Date: 14-06-2017
DOI: 10.2337/DC17-0626
Publisher: American Diabetes Association
Date: 11-07-2018
DOI: 10.2337/DC18-0551
Abstract: 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. We review potential contributors to excess fetal growth in pregnancies complicated by type 1 diabetes. In addition to hyperglycemia, we explore the role of glycemic variability, prepregnancy overweight and obesity, gestational weight gain, and maternal lipid levels. Greater understanding of the stimuli that drive excess fetal growth could lead to targeted management strategies in pregnant women with type 1 diabetes, potentially reducing the incidence of LGA neonates and the inherent risk of acute and long-term complications.
Publisher: Wiley
Date: 24-04-2018
Publisher: Elsevier BV
Date: 2020
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 02-03-2017
DOI: 10.5888/PCD14.160504
Publisher: Portland Press Ltd.
Date: 29-03-2018
DOI: 10.1042/BSR20180050
Abstract: Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all the different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk. Evidence suggests a strong link between the intrauterine environment and disease programming. The current review will describe the importance of the intrauterine environment in the development of metabolic disease, including kidney disease. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. The evidence for the role of maternal obesity in the developmental programming of CKD is derived mostly from our rodent models which will be described. The clinical implication of such findings will also be discussed.
Publisher: BMJ
Date: 06-2021
DOI: 10.1136/BMJDRC-2021-002277
Abstract: 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. Perinatal and hospital data were linked for singleton births, 33–41 weeks’ gestation, 2006–2015, NSW. An adjusted Poisson model was used to split pregnancies from 2011 onwards into those that would have been diagnosed under the old criteria (‘previous GDM’) and newly diagnosed cases (‘additional GDM’). We compared actual rates of total and early ( weeks) planned births, cesareans, and maternal and neonatal adverse outcomes for GDM-diagnosed pregnancies using three predicted scenarios, where the ‘additional GDM’ group was assumed to have the same rates as: the ‘previous GDM’ group (scenario A) the ‘non-GDM’ group (scenario B) or the ‘non-GDM’ group ≥2011 (scenario C). GDM incidence more than doubled over the study period, with an inflection point observed at 2011. For those diagnosed with GDM since 2011, the actual incidence of interventions (planned births and cesareans) and macrosomia was consistent with scenario A, which meant higher intervention rates, but lower rates of macrosomia, than those with no GDM. Incidence of neonatal hypoglycemia was lower than scenario A and closer to the other scenarios. There was a reduction in perinatal deaths among those with GDM, lower than that predicted by all scenarios, indicating an improvement for all with GDM, not only women newly diagnosed. Incidence of maternal and neonatal morbidity indicators was within the confidence bounds for all three predicted scenarios. Our study suggests that the widely adopted new diagnostic criteria for GDM are associated with increased obstetric intervention rates and lower rates of macrosomic babies, but with no clear impacts on maternal or neonatal morbidity.
Publisher: MDPI AG
Date: 23-05-2018
DOI: 10.3390/JCM7060120
Publisher: Bioscientifica
Date: 05-2021
DOI: 10.1530/EDM-20-0163
Abstract: 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. Further, therapeutic options are limited due to safety considerations for the pregnant woman and the developing foetus. Three cases of hypercalcaemia in pregnancy will be presented, highlighting the distinct aetiologies and management strategies for hypercalcaemia in pregnancy and the importance of early measurement of serum calcium in pregnancy screening. There are complex physiological changes in calcium balance in pregnancy, including increased calcium intestinal absorption and renal excretion. Hypercalcaemia in pregnancy is uncommon but has important potential maternal and foetal complications, making a compelling argument for routine antenatal, calcium screening. Identifying the cause of hypercalcaemia in pregnancy can be challenging due to the complex placental interplay in biochemical test interpretation and due to safety constraints restricting imaging and surgery. Acute medical management of hypercalcaemia must be considered in the context of both maternal and foetal well-being, along with gestational age and specific consideration for the safety of the developing fetus in late gestation.
Publisher: Springer Science and Business Media LLC
Date: 14-11-2015
Publisher: Springer Science and Business Media LLC
Date: 12-01-2017
DOI: 10.1038/JP.2016.254
Abstract: Gestational diabetes mellitus (GDM) in singleton pregnancy is associated with large for gestational age neonates and adverse perinatal outcomes however, the impact of GDM in twin pregnancy is unclear. Thus, the aim of this study is to assess the perinatal outcomes of twin pregnancies complicated by GDM by performing a meta-analysis of observational studies. Studies investigating GDM in twin pregnancy were identified through an online search of three databases: Medline, Embase and Web of Science. Selection criteria comprised full paper observational studies (retrospective or prospective) published in English that examined GDM in twin pregnancy compared with non-GDM twin pregnancy and reported on birth weight and/or adverse perinatal outcomes. Random-effects models with inverse-variance weighting were used to calculate standardized mean differences and unadjusted odds ratios. Sensitivity analyses were carried out to determine the impact of possible maternal confounders (body mass index and age) and GDM diagnostic criteria on perinatal outcomes. Thirteen observational studies were included. GDM twins were born at the same gestation as non-GDM twins, with marginally lower birth weight. There was no difference in the incidence of large or small for gestational age neonates. Although there was no correlation between GDM in twin pregnancy and respiratory distress, neonatal hypoglycemic or low Apgar score, GDM twins had a higher rate of neonatal intensive care unit admission (OR 1.49 95% confidence interval: 1.10, 2.02 P<0.01). Identification and subsequent treatment of GDM in twin pregnancy demonstrates a similar risk of adverse perinatal outcomes compared with non-GDM twin pregnancies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2021
DOI: 10.2215/CJN.01130121
Abstract: A reduction in the rate of eGFR decline, with preservation of ≥0.75 ml/min per 1.73 m 2 per year, has been proposed as a surrogate for kidney disease progression. We report results from prespecified analyses assessing effects of ertugliflozin versus placebo on eGFR slope from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease were randomized to placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg (1:1:1). The analyses compared the effect of ertugliflozin (pooled doses, n =5499) versus placebo ( n =2747) on eGFR slope per week and per year by random coefficient models. Study periods (weeks 0–6 and weeks 6–52) and total and chronic slopes (week 0 or week 6 to weeks 104, 156, 208, and 260) were modeled separately and by baseline kidney status. In the overall population, for weeks 0–6, the least squares mean eGFR slopes (ml/min per 1.73 m 2 per week [95% confidence interval (95% CI)]) were −0.07 (−0.16 to 0.03) and −0.54 (−0.61 to −0.48) for the placebo and ertugliflozin groups, respectively the difference was −0.47 (−0.59 to −0.36). During weeks 6–52, least squares mean eGFR slopes (ml/min per 1.73 m 2 per year [95% CI]) were −0.12 (−0.70 to 0.46) and 1.62 (1.21 to 2.02) for the placebo and ertugliflozin groups, respectively the difference was 1.74 (1.03 to 2.45). For weeks 6–156, least squares mean eGFR slopes (ml/min per 1.73 m 2 per year [95% CI]) were −1.51 (−1.70 to −1.32) and −0.32 (−0.45 to −0.19) for the placebo and ertugliflozin groups, respectively the difference was 1.19 (0.95 to 1.42). During weeks 0–156, the placebo-adjusted difference in least squares mean slope was 1.06 (0.85 to 1.27). These findings were consistent by baseline kidney status. Ertugliflozin has a favorable placebo-adjusted eGFR slope .75 ml/min per 1.73 m 2 per year, documenting the kidney function preservation underlying the clinical benefits of ertugliflozin on kidney disease progression in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease. US National Library of Medicine, ClinicalTrials.gov NCT01986881. Date of trial registration: November 13, 2013.
Publisher: MDPI AG
Date: 28-02-2023
DOI: 10.3390/NU15051226
Abstract: 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, preecl sia), and neonatal (hypoglycaemia, jaundice, respiratory distress and NICU admission) outcomes. This time frame encompassed a change in diagnostic criteria for gestational diabetes, due to changes in international consensus guidelines. Our results showed that, based on the diagnostic 75 g OGTT, fasting hyperglycaemia, either alone or in combination with elevated 1 or 2 h glucose levels, was associated with the need for pharmacotherapy with either metformin and/or insulin (p 0.0001 HR 4.02, 95% CI 2.88–5.61), as compared to women with isolated hyperglycaemia at the 1 or 2 h post-glucose load timepoints. Fasting hyperglycaemia on the OGTT was more likely in women with higher BMI (p 0.0001). There was an increased risk of early term birth in women with mixed fasting and post-glucose hyperglycaemia (adjusted HR 1.72, 95% CI 1.09–2.71). There were no significant differences in rates of neonatal complications such as macrosomia or NICU admission. Fasting hyperglycaemia, either alone or in combination with post-glucose elevations on the OGTT, is a strong indicator of the need for pharmacotherapy in pregnant women with GDM, with significant ramifications for obstetric interventions and their timing.
No related grants have been discovered for Sarah Glastras.