RESUMO
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. RESULTS: The HFD-fed mice developed obesity, with glucose intolerance, hyperinsulinaemia and dyslipidaemia. Obesity increased albuminuria and glomerulosclerosis, which were significantly ameliorated by low-dose hydralazine in the absence of a blood pressure-lowering effect. Obesity increased renal global DNA methylation and this was attenuated by low-dose hydralazine. HFD-induced changes in methylation of individual loci were also significantly reversed by low-dose hydralazine. Obese mice demonstrated increased markers of kidney fibrosis, inflammation and oxidative stress, but these markers were not significantly improved by hydralazine. CONCLUSION: Low-dose hydralazine ameliorated HFD-induced albuminuria and glomerulosclerosis, independent of alterations in biometric and metabolic variables or blood pressure regulation. Although the precise mechanism of renoprotection in obesity is unclear, an epigenetic basis may be implicated. These data support repurposing hydralazine as a novel therapy to prevent CKD progression in obese patients.
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Albuminúria , Insuficiência Renal Crônica , Albuminúria/tratamento farmacológico , Albuminúria/etiologia , Albuminúria/prevenção & controle , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fibrose , Hidralazina/farmacologia , Hidralazina/uso terapêutico , Inflamação/metabolismo , Rim , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
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.
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Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/metabolismo , Disbiose/metabolismo , Microbioma Gastrointestinal/fisiologia , Obesidade/metabolismo , Animais , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Ácidos Graxos Voláteis/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Obesidade/fisiopatologiaRESUMO
This is the full version of the Australasian Diabetes in Pregnancy Society (ADIPS) 2020 guideline for pre-existing diabetes and pregnancy. The guideline encompasses the management of women with pre-existing type 1 diabetes and type 2 diabetes in relation to pregnancy, including preconception, antepartum, intrapartum and postpartum care. The management of women with monogenic diabetes or cystic fibrosis-related diabetes in relation to pregnancy is also discussed.
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Guias de Prática Clínica como Assunto , Gravidez em Diabéticas , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Feminino , Humanos , Gravidez , Gravidez em Diabéticas/terapiaRESUMO
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. Epigenetic modifications are changes that regulate gene expression without altering the DNA sequence. Of these, DNA methylation is the most studied. Epigenetic imprints, particularly DNA methylation, are laid down during critical periods of fetal development, and they may provide a mechanism by which maternal-fetal transmission of chronic disease occurs. Our current review explores the evidence for the role of DNA methylation in the development of CKD, diabetic kidney disease, diabetes, and obesity. DNA methylation has been implicated in renal fibrosis-the final pathophysiologic pathway in the development of end-stage kidney disease-which supports the notion that demethylating agents may play a potential therapeutic role in preventing development and progression of CKD.-Larkin, B. P., Glastras, S. J., Chen, H., Pollock, C. A., Saad, S. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.
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Metilação de DNA/efeitos dos fármacos , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Falência Renal Crônica , Obesidade , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Humanos , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/metabolismo , Falência Renal Crônica/patologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/patologia , Fatores de RiscoRESUMO
BACKGROUND: Prevention of hospitalisation is an important aspect of type 2 diabetes (T2D) management. AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
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Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Hospitalização/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Idoso , Austrália/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Seguimentos , Humanos , Masculino , Admissão do Paciente , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
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.
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Rim/fisiopatologia , Obesidade/epidemiologia , Complicações na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal , Insuficiência Renal Crônica/epidemiologia , Animais , Autofagia , Meio Ambiente , Feminino , Humanos , Rim/metabolismo , Rim/patologia , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Obesidade/fisiopatologia , Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/fisiopatologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Medição de Risco , Fatores de Risco , Transdução de Sinais , Sirtuína 1/metabolismoRESUMO
INTRODUCTION: Chronic disease management programs (CDMPs) that include health coaching can facilitate and coordinate diabetes management. The aim of this study was to assess changes in patients' general knowledge of diabetes, self-reported health status, diabetes distress, body mass index (BMI), and glycemic control after enrollment in a face-to-face CDMP group health coaching session (with telephone follow-up) compared with participation in telephone-only health coaching, during a 12-month period. METHODS: Patients with diabetes were enrolled in a health coaching program at Royal North Shore Hospital, Sydney, Australia, in 2013. Questionnaires were administered at baseline and at 3, 6, and 12 months, and the results were compared with baseline. Glycemic control, measured with glycated hemoglobin A1c (HbA1c) and BMI, were measured at baseline and 12 months. RESULTS: Overall, 238 patients attended a face-to-face CDMP session with telephone follow-up (n = 178) or participated in telephone-only health coaching (n = 60). We found no change in BMI in either group; however, HbA1c levels in patients with baseline above the current recommended target (>7%) decreased significantly from 8.5% (standard deviation [SD], 1.0%) to 7.9% (SD, 1.0%) (P = .03). Patients with the lowest self-reported health status at baseline improved from 4.4 (SD, 0.5) to 3.7 (SD, 0.9) (P = .001). Diabetes knowledge improved in all patients (24.4 [SD, 2.4] to 25.2 [SD, 2.4]; P < .001), and diabetes distress decreased among those with the highest levels of distress at baseline (3.0 [SD, 0.4] vs 3.8 [SD, 0.6]; P = .003). CONCLUSION: Diabetes health coaching programs can improve glycemic control and reduce diabetes distress in patients with high levels of these at baseline.
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Diabetes Mellitus/terapia , Promoção da Saúde , Autocuidado/métodos , Austrália , Feminino , Humanos , Masculino , Autorrelato , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Diastolic dysfunction is a major cause of morbidity in obese individuals. We aimed to assess the ability of magnetic resonance imaging (MRI) derived left atrial (LA) strain to detect early diastolic dysfunction in individuals with obesity and type 2 diabetes, and to explore the association between cardiac adipose tissue and LA function. METHODS: 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. RESULTS: 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/m2, p < 0.001). There were significant correlations between LA functional indices and both BMI and EFV (p ≤ 0.007). CONCLUSIONS: LA MRI-strain may be a sensitive tool for the detection of early diastolic dysfunction in individuals 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.
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Tecido Adiposo/diagnóstico por imagem , Função do Átrio Esquerdo , Diabetes Mellitus Tipo 2/complicações , Cardiopatias/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Obesidade/complicações , Pericárdio/diagnóstico por imagem , Tecido Adiposo/fisiopatologia , Adiposidade , Adulto , Algoritmos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Diástole , Diagnóstico Precoce , Feminino , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/fisiopatologia , Pericárdio/fisiopatologia , Valor Preditivo dos Testes , Fatores de Risco , Função Ventricular EsquerdaRESUMO
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. Meta-analysis was conducted using a random effects model, to generate pooled estimates (odds ratios, OR, or mean difference, MD). Compared with normal-weight controls, women with obesity had increased risks of large for gestational age (LGA, OR 1.98, 95% CI: 1.56, 2.52) and macrosomia (OR 2.93, 95% CI: 1.71, 5.03); the latter's risk almost double in women with obesity than GDM. Birth weight (MD 113 g, 95% CI: 69, 156) and shoulder dystocia (OR 1.23, 95% CI: 0.85, 1.78) risk was also higher. GDM significantly amplified neonatal risk in women with obesity, with a three- to four-fold risk of LGA (OR 3.22, 95% CI: 2.17, 4.79) and macrosomia (OR 3.71, 95% CI: 2.76, 4.98), as well as higher birth weights (MD 176 g, 95% CI: 89, 263), preterm delivery (OR 1.49, 95% CI: 1.25, 1.77), and shoulder dystocia (OR 1.99, 95% CI: 1.31, 3.03), when compared with normal-weight controls. Our findings demonstrate that maternal obesity increases serious neonatal adverse risk, magnified by the presence of GDM. Effective strategies are needed to safeguard against neonatal complications associated with maternal obesity, regardless of GDM status.
Assuntos
Peso ao Nascer , Diabetes Gestacional , Macrossomia Fetal , Resultado da Gravidez , Humanos , Gravidez , Diabetes Gestacional/epidemiologia , Feminino , Recém-Nascido , Resultado da Gravidez/epidemiologia , Macrossomia Fetal/epidemiologia , Macrossomia Fetal/etiologia , Obesidade Materna/epidemiologia , Obesidade Materna/complicações , Fatores de Risco , Obesidade/complicações , Obesidade/epidemiologia , Complicações na Gravidez/epidemiologia , Distocia do Ombro/epidemiologiaRESUMO
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. C57BL/6 female mice were fed either a high-fat-diet (HFD) or a chow (control) diet for 8 weeks. To induce pre-pregnancy weight loss, HFD-fed dams were switched to chow diet (HFD-C) or administered liraglutide (0.3 mg/kg subcutaneous) whilst continuing on HFD (HFD-L). Liraglutide was discontinued one week prior to mating. HFD-V mice continued on HFD, with saline injections. A group of HFD-fed dams were 'diet switched' to chow after conception (post-conception, HFD-PC). Maternal body weight and glucose tolerance were measured: (1) preconception and (2) during late gestation followed by blood, urine and kidney collection. Serum creatinine, urinary creatinine and albumin, kidney tissue gene expression and protein were measured. In the preconception period, HFD-L and HFD-C mothers have lower urine albumin:creatinine ratios (UACR) and fatty acid synthase (FAS) protein expression (P < 0.005 vs. HFD-V). At late gestation, kidneys of HFD-V and HFD-PC dams have increased gene expression of insulin receptor and FAS (P < 0.05) and higher UACR compared to controls (P < 0.01). In the HFD-PC group, kidneys show increased mRNA and protein expression of metabolic and oxidative stress markers (FAS, 8-OHdG vs. control, P < 0.05, P < 0.0001 respectively). The preconception intervention groups with liraglutide, or diet change show reduced oxidative stress (protein expression of 8-OHdG, P < 0.05 vs. HFD), mRNA and protein expression of FAS (P < 0.05 vs. HFD), protein expression of fibrosis markers (collagen IV, fibronectin vs. HFD, P < 0.05), and UACR (P < 0.05 vs. HFD). This study suggests that preconception weight loss benefits maternal kidney health during pregnancy, superior to diet intervention once already pregnant.
Assuntos
Dieta Hiperlipídica , Rim , Camundongos Endogâmicos C57BL , Obesidade , Animais , Feminino , Gravidez , Rim/metabolismo , Camundongos , Obesidade/metabolismo , Dieta Hiperlipídica/efeitos adversos , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Redução de Peso , Peso CorporalRESUMO
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.
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Mães , Hepatopatia Gordurosa não Alcoólica , Gravidez , Humanos , Feminino , Estudos Prospectivos , ObesidadeRESUMO
BACKGROUND: Gestational diabetes mellitus (GDM) is experienced at a higher rate in women from culturally and linguistically diverse (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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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Diabetes Gestacional , Gravidez , Humanos , Feminino , Diabetes Gestacional/diagnóstico , Estudos Transversais , Atenção à Saúde , Pessoal de Saúde/psicologia , DietaRESUMO
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. The development of both conditions is underpinned by the upregulation of oxidative stress pathways and consequential inflammation and hypoxia. In oxidative stress, there is an imbalance of reactive oxygen species and nitric oxide. Endothelial nitric oxide synthase becomes uncoupled in disease states, producing superoxide and worsening oxidative stress. Agonist stimulation of the beta-3 adrenoreceptor recouples and activates endothelial nitric oxide synthase, increasing the production of nitric oxide. This reduces circulating reactive oxygen species, thus decreasing redox modification and dysregulation of cellular proteins, causing downstream smooth muscle relaxation, improved endothelial function and increased angiogenesis. These mechanisms lead to endothelial repair in peripheral arterial disease and an enhanced perfusion in hypoxic tissue, which will likely improve the healing of chronic ulcers.
RESUMO
Introduction: Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes in many countries worldwide, including Australia. Although studies have explored the experiences of women with GDM from ethnic minority groups, few have compared their experiences with women from Anglosphere backgrounds. Objective: To investigate the responses to diagnosis, the management of GDM, and the experiences of healthcare services among women with GDM from different culturally and linguistically diverse (CALD) backgrounds. Methods: Participants were recruited via convenience sampling by advertisement posted around antenatal clinics of three hospitals in NSLHD: Royal North Shore, Hornsby, and Manly Hospitals. The interviews were semi-structured, one-on-one, and in-person conducted by a trained female volunteer. The interviews were audio-recorded, transcribed into text. The data was analyzed via an inductive and descriptive coding approach. The codes were then categorized into main themes and sub-themes. Results: 30 women (7 Australian-born, 11 Chinese, 8 Indians, and 4 Koreans) partook the semi-structured interviews and 5 themes were identified: (1) Reaction to diagnosis; (2) Management issues; (3) Roles of friends and family; (4) Information access; and (5) Experience with healthcare services. The lack of culturally tailored dietary information, social support and language barriers were the main factors underpinning the differences in GDM experiences among women from CALD backgrounds versus Australian-born. Conclusion: Healthcare models should provide more emotional support upon diagnosis, culturally tailored guidelines for lifestyle modifications, and involve friends and family in care and management to enhance the experience of GDM for women from CALD backgrounds.
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Diabetes Gestacional , Humanos , Feminino , Gravidez , Austrália , Etnicidade , Grupos Minoritários , Pesquisa QualitativaRESUMO
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. 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.
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Diabetes Gestacional , Hiperglicemia , Hipoglicemia , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Diabetes Gestacional/epidemiologia , Teste de Tolerância a Glucose , Estudos Retrospectivos , Cesárea , Austrália , Glucose , Jejum , Glicemia/metabolismo , Resultado da Gravidez/epidemiologiaRESUMO
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. HFD-fed mice either continued HFD, transitioned to a chow diet, or were administered liraglutide for 4 weeks. Pregnancy was induced following a one-week washout of liraglutide during which all animals remained on their respective diets. A proportion of HFD-fed mice transitioned to a chow diet during pregnancy. All offspring were weaned to the HFD. Offspring anthropometric, metabolic, and hepatic outcomes were assessed at postnatal week 12. The offspring of mothers with obesity had phenotypic changes consistent with MAFLD. The offspring of mothers that had weight loss with perinatal dietary intervention had reduced insulin resistance (p < 0.001) and hepatic expression of markers of inflammation (p < 0.001), oxidative stress (p < 0.05), and fibrosis (p < 0.05). A similar phenotype was observed in the offspring of mothers with pre-pregnancy weight loss via liraglutide despite ongoing consumption of the HFD during pregnancy. All methods and timing of maternal weight intervention were effective at ameliorating adverse liver effects in the offspring.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hepatopatia Gordurosa não Alcoólica , Humanos , Gravidez , Feminino , Animais , Camundongos , Liraglutida , Obesidade , Mães , Redução de PesoRESUMO
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. Methods: We retrospectively analysed data from all singleton births from mothers with obesity from 2013-2017 in Northern Sydney Local Health District in Sydney, Australia. Women were categorised into obesity class I (BMI 30-34.9kg/m2), class II (BMI 35-39.9 kg/m2) or class III (BMI 40+ kg/m2). Across BMI classes, we compared maternal outcomes including mode of delivery, gestational diabetes mellitus (GDM), and preeclampsia, and neonatal outcomes including large- and small-for-gestational age (SGA, LGA), neonatal hypoglycaemia, birth defects and timing of birth. Logistic analyses were performed to explore the impact of maternal obesity class on these outcomes, adjusting for maternal age, country of birth, parity, diabetes (both pre-existing and gestational) and hypertension. Results: There were 2466 births to women with obesity, class (69.1%), class II (21.8%), and class III (9.2%). 42.5% delivered by Caesarean section, 22.3% developed GDM and 11.2% had a hypertensive disorder in pregnancy, and Caesarean section and GDM were more common in women with higher class obesity. LGA occurred in 27.3% and SGA occurred in 4.0% of women across all classes of obesity. LGA rates were 49% more likely in women with class III compared to women with class I obesity (OR=1.49, CI 1.06-2.09, p=0.02). The presence of diabetes in the index pregnancy did not significantly impact risk of neonatal LGA between maternal obesity classes. Other neonatal adverse outcomes such as stillbirth and birth defects were more common in women with higher class obesity. SGA, neonatal hypoglycaemia, gestational age at delivery, APGAR 5-minute score and NICU admissions were similar across obesity classes, after adjustment for covariates. Conclusions: Obesity class increases the risk of many adverse maternal and neonatal outcomes. Obesity class is independently associated with LGA incidence in the neonate, independent of maternal factors including GDM. Ongoing efforts must be made to reduce obesity incidence in women of reproductive age to circumvent the adverse perinatal outcomes associated with obesity.
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Diabetes Gestacional , Hipoglicemia , Obesidade Materna , Índice de Massa Corporal , Cesárea , Diabetes Gestacional/epidemiologia , Feminino , Humanos , Hipoglicemia/complicações , Recém-Nascido , Obesidade/complicações , Obesidade/epidemiologia , Gravidez , Estudos RetrospectivosRESUMO
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.
Assuntos
Obesidade Materna , Animais , Feminino , Feto/metabolismo , Humanos , Obesidade/metabolismo , Placenta/metabolismo , Gravidez , RoedoresRESUMO
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. A common theme is late identification and delay in diagnosis. Hence, we discuss the clinical features, need for clinicopathological correlation, and the management and prognostic implications for this distinctive entity. While most remain relatively asymptomatic, others progress to debilitating disease with pruritus, dysesthesia, and pain. Pain is often intense in the presence of ulcerated plaques, a morbid complication of NL. Diagnosis requires the integration of both clinical and histopathological findings. NL has proven a challenging condition to treat, and despite the numerous therapeutic modalities available, there is no standard of care. Hence, in this study, we provide an overview of current management strategies available for NL. Learning points: Necrobiosis lipoidica (NL) is classically seen in patients with type 1 diabetes. Koebner phenomenon, defined as the appearance of new skin lesions on previously unaffected skin secondary to trauma, is a well-recognised feature in NL. Background skin phototype contributes to variable yellow appearance of lesions in NL. Diagnosis of NL requires careful clinicopathological correlation. NL is a chronic disease often refractory to treatment leading to significant morbidity for the patient and a management conundrum for the multidisciplinary healthcare team. No standard therapeutic regimen has been established for the management of NL.
RESUMO
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.