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1.
Intern Med J ; 51(1): 78-86, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32237194

RESUMO

BACKGROUND: Understanding the risk factors and pregnancy outcomes in women affected by Type 1 and Type 2 diabetes is important for pre-pregnancy counselling. AIM: To explore differences in pregnancy outcomes between women with Type 1 and Type 2 diabetes, and healthy controls, and to examine the relationships between potential adverse risk factors and pregnancy outcomes in this cohort of women. METHODS: This is a 10-year retrospective study of women with Type 1 diabetes (n = 92), Type 2 diabetes (n = 106) and healthy women without diabetes (controls) (n = 119) from a tertiary obstetric centre. Clinical and biochemical characteristics of women with Type 1 and Type 2 diabetes were determined and related to major obstetric outcomes using univariate analysis. RESULTS: Women with pre-existing diabetes had higher adverse pregnancy outcomes (preeclampsia, emergency caesarean section, preterm birth <32 and 37 weeks, large for gestational age, neonatal jaundice, Apgar score < 7 at 5 min, neonatal intensive care admission and neonatal hypoglycaemia) compared to controls. A higher birth weight gestational centile (97.4% vs 72.4%, P = 0.001) and large for gestational age rate (63.4% vs 35.8%, P = 0.001) were observed in Type 1 diabetes compared to Type 2 diabetes. There were no differences in other outcomes between women with Type 1 and 2 diabetes. CONCLUSION: In this exploratory study, risk factors for maternal adverse outcomes differ between Type 1 and Type 2 diabetes. Maternal and foetal adverse outcomes were higher in pregnancies affected by diabetes compared to healthy women but occurred with similar frequency in women with Type 1 and Type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Nascimento Prematuro , Cesárea , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , Fatores de Risco
2.
Eur J Cancer Care (Engl) ; 29(2): e13216, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31943459

RESUMO

OBJECTIVE: To determine availability of nutrition information for cancer patients and survivors from Irish healthcare organisations, cancer charity and support groups and assess its quality and readability. DESIGN: Cross-sectional. SETTING: The National Health Service Executive websites were searched, as were the sites of the ten largest cancer charities/support groups identified through the Benefacts website. An additional internet search was conducted to ensure no large organisations/support groups were missed (February 2019). Quality of nutrition content was assessed using an evidence-based checklist and readability assessed using two validated formulas. RESULTS: Thirty-two websites were identified, five contained nutrition information for cancer patients (15.6%), and three for cancer survivors (9.3%). The quality of the nutrition content ranged from 19.5 to 29/40 (mean ± SD, 23.2 ± 3.2; median = 21, interquartile range (IQR) = 7). There was a lack of practical strategies for implementation. Only 40% of material had an acceptable readability level (sixth-seventh grade level). Readability scores (mean ± SD) were 68.5 ± 6.0 for Flesch Reading Ease Score and 7.8 ± 1.1 for Flesch-Kincaid Grade Level Score. CONCLUSION: There is limited nutrition information on Irish health and cancer websites and in particular very few tailored to cancer survivors. Irish health and cancer organisations should consider providing nutrition information that is easily accessible to all.


Assuntos
Compreensão , Informação de Saúde ao Consumidor , Internet , Neoplasias , Política Nutricional , Terapia Nutricional , Institutos de Câncer , Sobreviventes de Câncer , Instituições de Caridade , Estudos Transversais , Humanos , Irlanda
3.
Intern Med J ; 49(8): 994-1000, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30561039

RESUMO

BACKGROUND: Interest in potential adverse outcomes associated with maternal subclinical hypothyroidism (normal free T4, elevated thyroid-stimulating hormone (TSH)) has increased significantly over recent years. In turn, the frequency of maternal thyroid function testing has risen, despite universal thyroid function screening not being recommended, leading to a marked increase in referrals to obstetric endocrinology clinics. In 2017 the American Thyroid Association revised their diagnostic and management guidelines. Although welcome, these new guidelines contain recommendations that may cause confusion in clinical practice. AIM: To ensure uniform practice in the diagnosis and management of subclinical hypothyroidism in pregnancy across all Melbourne public hospitals. METHODS: Endocrinology and obstetric representatives from all Melbourne public hospital networks reviewed the 2017 American Thyroid Association guidelines and other relevant literature to develop a consensus for diagnosing and treating subclinical hypothyroidism during pregnancy in Melbourne. The consensus guidelines were then referred to the Endocrine Society of Australia for comment and endorsement. RESULTS: Consensus was achieved and the guidelines were endorsed by the Council of the Endocrine Society of Australia. Trimester and assay-specific TSH reference intervals derived from healthy local populations should be used, where available. When unavailable, a TSH cut-off of 4 mU/L (replacing the previously recommended 2.5 mU/L) should be used to initiate treatment, irrespective of thyroid auto-antibody status. The recommended starting dose of levothyroxine is 50 µg daily, with a therapeutic TSH target of 0.1-2.5 mU/L. Levothyroxine should generally be ceased after delivery, with some exceptions. Hospitals will ensure smooth transfer of care back to the woman's general practitioner with clear documentation of pregnancy thyroid management and a recommended plan for follow-up. CONCLUSION: Fewer women will be classified as having subclinical hypothyroidism during pregnancy, which is likely to lead to reductions in emotional stress, hospital visits, repeated blood tests and financial costs. Uniform clinical practice will occur across Melbourne.


Assuntos
Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico , Tiroxina/administração & dosagem , Adulto , Austrália , Consenso , Feminino , Hospitais Públicos , Humanos , Hipotireoidismo/sangue , Guias de Prática Clínica como Assunto , Gravidez , Complicações na Gravidez/sangue , Valores de Referência , Testes de Função Tireóidea
4.
Aust N Z J Obstet Gynaecol ; 59(1): 96-101, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29672829

RESUMO

BACKGROUND: Recent guidelines suggest screening high-risk women in early pregnancy for gestational diabetes (GDM); however, there is little evidence to support this. AIMS: To compare pregnancy outcomes associated with diabetes for women with risk factors for GDM according to gestation of diagnosis. Early GDM was defined as a positive test before 20 weeks gestation, late GDM as a positive test at 20 or more weeks and no GDM when both tests were negative. MATERIALS AND METHODS: Retrospective analysis in an Australian tertiary hospital of women who underwent a glucose tolerance test in pregnancy prior to 20 weeks gestation, and a repeat test after 20 weeks gestation if the initial test was negative. Results were adjusted for maternal demographics. RESULTS: Women with early GDM (n = 170) were no more likely to experience the obstetric composite outcome than women with late GDM (n = 171) or no GDM (n = 547) (early odds ratio (OR) 1.16, 95%CI 0.79-1.71; late OR 0.78, 95%CI 0.53-1.12). Infants of women with early GDM, but not late GDM, were more likely (early OR 1.8, 95%CI 1.15-2.92; late OR 1.4, 95%CI 0.90-2.23) to have the neonatal composite outcome than infants of women without GDM, predominantly due to an increase in neonatal hypoglycaemia. CONCLUSIONS: This result may be due to careful management of GDM, or because, after adjustment for maternal demographics, the early diagnosis of GDM does not substantially increase rates of adverse outcomes compared to GDM diagnosed in later pregnancy or no GDM in women with risk factors for GDM.


Assuntos
Diabetes Gestacional/diagnóstico , Diagnóstico Pré-Natal , Adulto , Estudos de Coortes , Feminino , Teste de Tolerância a Glucose , Humanos , Gravidez , Resultado da Gravidez , Trimestres da Gravidez , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Fatores de Tempo , Vitória
5.
Med J Aust ; 201(4): 224-6, 2014 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-25164851

RESUMO

OBJECTIVE: To investigate the safety, tolerability and efficacy of combination phentermine and topiramate therapy for maintenance of weight loss. DESIGN, SETTING AND PATIENTS: Retrospective audit of patients attending the Austin Health Weight Control Clinic who were dispensed phentermine-topiramate between 22 January 2010 and 16 July 2012 and after reaching a target weight by following a very low energy diet (VLED). Data collection continued until July 2013. MAIN OUTCOME MEASURES: Number of patients who ceased pharmacotherapy; duration of use of pharmacotherapy; types and numbers of adverse effects; and mean weight and blood pressure measurements at the initial visit, the end of the VLED and the last observation during pharmacotherapy. RESULTS: Data were available for 103 patients who were dispensed phentermine-topiramate; 61 patients ceased combination pharmacotherapy before the end of the data collection period, 41 due to adverse effects (eg, paraesthesia, cognitive changes, dry mouth and depression). The mean duration of use of pharmacotherapy was 10 months. Mean weight decreased by 10% due to the VLED (from 135.5 kg to 122.5 kg) and this loss was maintained. For 30 patients who continued on phentermine-topiramate, the mean duration of pharmacotherapy was 22 months and the mean weight decreased by 6.7 kg between the end of the VLED and the last observation during pharmacotherapy. CONCLUSION: Phentermine-topiramate therapy was not well tolerated; more than half of the patients in our study stopped taking it because of adverse effects, and more than half of the adverse events reported were ascribed to topiramate. However, in those able to continue with pharmacotherapy, the combination was efficacious for both maintenance of weight loss and ongoing weight loss.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Frutose/análogos & derivados , Obesidade/tratamento farmacológico , Fentermina/administração & dosagem , Redução de Peso , Fármacos Antiobesidade/efeitos adversos , Austrália/epidemiologia , Índice de Massa Corporal , Quimioterapia Combinada , Seguimentos , Frutose/administração & dosagem , Frutose/efeitos adversos , Humanos , Auditoria Médica , Obesidade/epidemiologia , Fentermina/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Topiramato , Falha de Tratamento , Resultado do Tratamento , Redução de Peso/efeitos dos fármacos
7.
Eur J Clin Nutr ; 76(6): 819-826, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34716363

RESUMO

BACKGROUND/OBJECTIVES: The aims of this study were to (1) document currently available guidelines aimed at healthcare professionals and including some information on the nutritional management of cancer survivors in Europe; (2) assess the quality of these guidelines and (3) document the nutrition recommendations promoted. METHODS: Four search strategies were implemented in 2018 and updated in 2021 to locate guidelines. Papers were included if they described a European guideline or recommendation for cancer survivors that contained nutrition guidance and there were no language restrictions. Two reviewers independently assessed guideline quality using the AGREE II instrument and nutrition content was extracted and summarised. RESULTS: Five guidelines (of 593 documents located through the searches) met the inclusion criteria. The ESPEN guidelines were deemed to have the highest methodological quality. Limited information on nutrition was available in these guidelines with the majority of focus being on the promotion of fruit, vegetables and wholegrains and reducing fat, red meat and alcohol. Weight management was mentioned by all five guidelines. There was no detailed information available for cancer survivors or their healthcare team and no practical strategies for the implementation of recommendations. CONCLUSIONS: There is a need for nutrition guidelines specific for cancer survivors in a European setting. Current guidelines are limited and focus on broad recommendations, while lacking in practical strategies for implementation. There is also a tendency to recommend cancer prevention guidelines be used for cancer survivors rather than developing specific guidance for this group.


Assuntos
Sobreviventes de Câncer , Neoplasias , Europa (Continente) , Humanos , Neoplasias/terapia , Política Nutricional , Equipe de Assistência ao Paciente , Verduras
8.
Aust N Z J Obstet Gynaecol ; 51(1): 22-5, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21299504

RESUMO

BACKGROUND: To reduce the number of patients needing oral glucose tolerance test (OGTT), screening options have been considered, balancing patient comfort, cost and risk of missed diagnosis. Australian Diabetes in Pregnancy Society (ADIPS) recommends glucose challenge test (GCT) as screening for gestational diabetes mellitus (GDM), while others suggest fasting plasma glucose (FPG). International Association of Diabetes and Pregnancy Study Group (IADPSG) recently recommended new diagnostic criteria for GDM using one-step OGTT. AIM: (i) To determine how many GDM patients would be missed with GCT/OGTT or FPG/OGTT compared to OGTT alone. (ii) To assess GCT in screening for GDM using new IADPSG criteria. METHODS: Austin Pathology database was searched from 2005 to 2007; 8486 episodes of GCT and OGTT were found. Test characteristics were determined for: (i) Simulated GCT/OGTT, where the 60-min OGTT value was regarded as equivalent to 60-min GCT value; (ii) Simulated FPG/OGTT, investigating the utility of different FPG values to indicate need for OGTT. RESULTS: Oral glucose tolerance test (one-step procedure): Of 5473 patients who had OGTT alone, 14% had GDM (ADIPS criteria). Actual GCT/OGTT: Of 2407 GCT, 17.3% were abnormal, with 75% having normal follow-up OGTT. Simulated studies: In the simulated GCT/OGTT, using ADIPS criteria, GCT had a sensitivity of 87%, specificity of 74% and would miss 13% of cases. Although simulated FG/OGTT had similar sensitivity of 82% for FPG ≥4.4 mmol/L, specificity was 42%. Using IADPSG criteria, 19% were diagnosed with GDM, screening GCT had a sensitivity of 83%, specificity of 75% and would miss 17% of cases. CONCLUSION: Oral glucose tolerance test alone is the best procedure without prior preliminary testing.


Assuntos
Diabetes Gestacional/diagnóstico , Teste de Tolerância a Glucose/métodos , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Austrália , Diabetes Gestacional/epidemiologia , Erros de Diagnóstico/estatística & dados numéricos , Feminino , Humanos , Guias de Prática Clínica como Assunto , Gravidez , Distribuição Aleatória , Sensibilidade e Especificidade
9.
Dev Med Child Neurol ; 52(2): e35-41, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19811518

RESUMO

AIM: To assess the accuracy of skinfold equations in estimating percentage body fat in children with cerebral palsy (CP), compared with assessment of body fat from dual energy X-ray absorptiometry (DXA). METHOD: Data were collected from 71 participants (30 females, 41 males) with CP (Gross Motor Function Classification System [GMFCS] levels I-V) between the ages of 8 and 18 years. Estimated percentage body fat was computed using established (Slaughter) equations based on the triceps and subscapular skinfolds. A linear model was fitted to assess the use of a simple correction to these equations for children with CP. RESULTS: Slaughter's equations consistently underestimated percentage body fat (mean difference compared with DXA percentage body fat -9.6/100 [SD 6.2]; 95% confidence interval [CI] -11.0 to -8.1). New equations were developed in which a correction factor was added to the existing equations based on sex, race, GMFCS level, size, and pubertal status. These corrected equations for children with CP agree better with DXA (mean difference 0.2/100 [SD=4.8]; 95% CI -1.0 to 1.3) than existing equations. INTERPRETATION: A simple correction factor to commonly used equations substantially improves the ability to estimate percentage body fat from two skinfold measures in children with CP.


Assuntos
Tecido Adiposo/patologia , Paralisia Cerebral/patologia , Dobras Cutâneas , Absorciometria de Fóton/métodos , Adolescente , Algoritmos , Antropometria/métodos , Paralisia Cerebral/diagnóstico , Criança , Avaliação da Deficiência , Feminino , Humanos , Masculino , Análise de Regressão , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
10.
Diabetes Res Clin Pract ; 165: 108225, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32442556

RESUMO

AIMS: To investigate the prognostic value of estimated glomerular filtration rate (eGFR) and albuminuria in determining pregnancy outcomes in women with type 1 and type 2 diabetes. METHODS: An observational study of pregnant women with type 1 (n = 92) and type 2 diabetes (n = 106) who delivered between 2004 and 2014 at a single tertiary obstetric centre. Clinical and biochemical characteristics were determined and related to major obstetric outcomes: preeclampsia, preterm birth <32 and <37 weeks, and neonatal intensive care admission. We used univariate analyses and multivariable logistic regression models with eGFR using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and albuminuria as covariates. RESULTS: In the pooled diabetes cohort, multivariable logistic regression with eGFR and albuminuria status demonstrated that the presence of albuminuria (albumin-to-creatinine ratio ≥ 3.5 mg/mmol) (OR, 2.7; 95% CI, 1.42-4.99; P = 0.002) was associated with preeclampsia, whilst an eGFR of < 120 mL/min/1.73 m2 was associated with preterm birth < 32 weeks (OR, 1.04; 95% CI, 1.00-1.09; P = 0.02). CONCLUSIONS: Despite its recognized limitations in pregnancy, lower eGFR values were associated with increased risk of adverse outcomes. Our exploratory data suggest eGFR, along with albuminuria, can aid in identifying women at high risk of developing adverse obstetric outcomes.


Assuntos
Albuminúria/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Taxa de Filtração Glomerular , Rim/fisiopatologia , Adulto , Albuminúria/diagnóstico , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva Neonatal , Testes de Função Renal , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Gravidez , Resultado da Gravidez , Nascimento Prematuro/diagnóstico , Nascimento Prematuro/epidemiologia , Prognóstico , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco
11.
Diabetes Technol Ther ; 22(11): 822-827, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32324046

RESUMO

Background: Gestational diabetes mellitus (GDM) management using self-monitoring blood glucose (SMBG) does not normalize pregnancy outcomes. Objective: We aimed to conduct an observational study to explore if continuous glucose monitoring (CGM) could identify elevated glucose levels not apparent in women with GDM managed using SMBG. Study Design: A 7-day masked-CGM (iPro; Medtronic) was performed within 2 weeks of GDM diagnosis, immediately post-GDM education, but before insulin commencement as determined by SMBG. CGM data regarding hyperglycemia (sensor glucose >126 mg/dL [06:00-00:00 h] and >99 mg/dL [00:00-06:00 h] for >10% of time), time with health care professionals, treatment, and pregnancy outcome were collected. Comparisons (Mann-Whitney test) were performed between subjects subsequently commenced on insulin versus those continued with diet and lifestyle measures alone. Results: Ninety women of mean (standard deviation) gestational age weeks 27(1) were studied. Those prescribed insulin (n = 34) compared with those managed with diet and lifestyle alone (n = 56) had a greater time in hyperglycemia (P = 0.0001). Of those not prescribed insulin, 35/56 (61%) breached CGM cutoffs between 00:00 and 06:00 h; 11/56 (20%) breached 6.00-00.00 h CGM cutoffs for >10% of the time; and 21/45 (47%) with optimal CGM glucose levels during the daytime spent >10% time in hyperglycemia between 00.00 and 06:00 h. In contrast, SMBG measurements exceeded the clinical targets of <120 mg/dL postdinner in 5.4% and <100 mg/dL fasting in 0% of the subjects. Conclusions: CGM provides a more comprehensive assessment of nocturnal hyperglycemia than SMBG and could improve targeting of interventions in GDM. Larger studies to better define CGM targets are required, which once established will inform studies aimed at targeting nocturnal glucose levels.


Assuntos
Automonitorização da Glicemia , Diabetes Gestacional , Glicemia/análise , Diabetes Gestacional/diagnóstico , Feminino , Humanos , Gravidez
12.
Artigo em Inglês | MEDLINE | ID: mdl-30108547

RESUMO

Large birthweight, or macrosomia, is one of the commonest complications for pregnancies affected by diabetes. As macrosomia is associated with an increased risk of a number of adverse outcomes for both the mother and offspring, accurate antenatal prediction of fetal macrosomia could be beneficial in guiding appropriate models of care and interventions that may avoid or reduce these associated risks. However, current prediction strategies which include physical examination and ultrasound assessment, are imprecise. Biomarkers are proving useful in various specialties and may offer a new avenue for improved prediction of macrosomia. Prime biomarker candidates in pregnancies with diabetes include maternal glycaemic markers (glucose, 1,5-anhydroglucitol, glycosylated hemoglobin) and hormones proposed implicated in placental nutrient transfer (adiponectin and insulin-like growth factor-1). There is some support for an association of these biomarkers with birthweight and/or macrosomia, although current evidence in this emerging field is still limited. Thus, although biomarkers hold promise, further investigation is needed to elucidate the potential clinical utility of biomarkers for macrosomia prediction for pregnancies affected by diabetes.

13.
Obes Res Clin Pract ; 12(2): 139-145, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29170078

RESUMO

BACKGROUND: Although population-based studies indicate that on average, women gain 1-2kg between pregnancies, women with obesity often attribute its development to childbearing. There is little contemporary data available regarding how commonly this occurs, particularly in women of different body mass index (BMI) categories. The aim of this study was to examine inter-pregnancy weight changes among women at a tertiary obstetric hospital in Melbourne, Australia. METHODS: This was a retrospective review of data from the Birthing Outcomes System electronic record of 19,617 women aged 20 years or older, who delivered at least two consecutive singleton infants at ≥37 weeks' gestation at Mercy Hospital for Women between December 1994 and December 2015. A logistic regression model was used to assess the relationship between gain of ≥4kg/m2 between pregnancies and maternal BMI category in the first pregnancy, adjusting for covariates of maternal age, inter-pregnancy interval, and socioeconomic status. RESULTS: Gain of ≥4kg/m2 between the first two pregnancies occurred in 7.5% of normal weight women, 10.5% of overweight women, and 13.4% of women with obesity. One in five women who were normal weight in their first pregnancy increased to overweight or obese BMI categories in their second pregnancy. CONCLUSIONS: Substantial weight gain in relation to pregnancy affects a considerable proportion of women. Since inter-pregnancy weight gain is associated with several complications in the next pregnancy and longer term, avoiding excessive weight gain during and between pregnancies may prevent adverse health consequences in mothers and offspring.


Assuntos
Mães , Obesidade/epidemiologia , Complicações na Gravidez , Aumento de Peso/fisiologia , Adulto , Austrália/epidemiologia , Índice de Massa Corporal , Feminino , Humanos , Idade Materna , Obesidade/etiologia , Obesidade/fisiopatologia , Paridade , Gravidez , Complicações na Gravidez/fisiopatologia , Prevalência , Estudos Retrospectivos , Classe Social
14.
Obstet Med ; 10(2): 83-84, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28680468

RESUMO

A 26-year-old primigravida at 35 weeks' gestation was transferred to our institution from a regional hospital for management of presumed preeclampsia. Due to the labile nature of her hypertension, further investigation was undertaken which revealed a right-sided phaeochromocytoma. Alpha blockade was commenced, and an uncomplicated elective caesarean delivery was performed at 38 weeks' gestation under spinal anaesthetic. The patient underwent an elective right laparoscopic adrenalectomy six weeks post-partum. This case highlights the importance of investigating young women for secondary causes of hypertension to avoid mislabelling as essential or gestational hypertension.

15.
J Diabetes Investig ; 8(5): 697-700, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28129477

RESUMO

It is unknown if high prolactin levels during pregnancy contribute to the development of gestational diabetes. We hypothesized that higher prolactin levels are associated with reduced glucose tolerance, as determined by higher 2-h glucose level from an oral glucose tolerance test in pregnancy. The 75-g oral glucose tolerance test was carried out at 28 weeks of gestation in 69 participants. A multiple regression analysis was used to determine the relationship between serum prolactin and 2-h glucose levels. Multivariable regression analysis showed an independent and significant relationship between third trimester prolactin and 2-h glucose levels post oral glucose tolerance test. Higher prolactin levels were associated with higher glucose levels independent of age, body mass index, gravidity and parity. Higher prolactin levels associated with reduced glucose tolerance in the third trimester of pregnancy suggests the possible independent role of prolactin in the pathogenesis of gestational diabetes.


Assuntos
Glicemia/metabolismo , Prolactina/sangue , Adulto , Diabetes Gestacional/sangue , Feminino , Idade Gestacional , Teste de Tolerância a Glucose , Humanos , Gravidez , Terceiro Trimestre da Gravidez
16.
J Clin Endocrinol Metab ; 91(1): 239-47, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16263824

RESUMO

CONTEXT: Combined pituitary hormone deficiency (CPHD) in humans is caused by mutations of pituitary-specific transcription factors such as Pit-1. Although many patients with CPHD have an autosomal recessive disorder caused by a Pit-1 DNA-binding mutation, there are a number of reports of mutant Pit-1 molecules that either by prediction or through experimentation bind normally to DNA. OBJECTIVE: The objective of this study was to understand the pathophysiological mechanisms of mutant Pit-1 molecules with intact DNA binding. DESIGN: DNA-binding and functional studies were used to assess five Pit-1 mutations: F135C, R143Q, A158P, K216E, and R271W. RESULTS: In gel-shift studies using well-characterized DNA-binding elements from the GH and prolactin genes, the K126E mutant displayed markedly enhanced Pit-1 dimer binding to either element, whereas the R271W mutant bound with high avidity, but only as a monomer. In contrast, the R143Q mutant was unable to bind these elements, and the F135C and A158P mutants displayed near-normal DNA-binding characteristics. We observed that CBP/p300 bound poorly to the A158P and K216E mutant Pit-1 molecules, but bound normally to the F135C, R143Q, and R271W mutants. In functional assays, CBP/p300 cotransfection with mutant Pit-1 expression vectors resulted in less transactivation of either the GH or prolactin reporter genes. CONCLUSIONS: From these studies, we suggest that CBP/p300 recruitment and Pit-1 dimerization are necessary for Pit-1 target gene activation and are important in the pathogenesis of CPHD.


Assuntos
Hipopituitarismo/genética , Hormônios Hipofisários/deficiência , Fator de Transcrição Pit-1/genética , Fatores de Transcrição de p300-CBP/fisiologia , Sequência de Bases , Células Cultivadas , Ensaio de Desvio de Mobilidade Eletroforética , Genes Reporter/genética , Humanos , Luciferases/genética , Modelos Moleculares , Ligação Proteica , Ativação Transcricional/genética , Transfecção
17.
Diabetes Care ; 25(6): 1072-7, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12032117

RESUMO

OBJECTIVE: Transforming growth factor-beta (TGF-beta) is a prosclerotic growth factor implicated in the pathogenesis of diabetic nephropathy. In addition to high glucose, other factors implicated in renal fibrosis and increased TGF-beta synthesis include angiotensin II and high dietary sodium intake. The aim of this study was to examine the effect of angiotensin receptor blockade (ARB) and dietary sodium restriction on the plasma concentration and urinary excretion of TGF-beta in hypertensive patients with type 2 diabetes and elevated albumin excretion rate (AER). RESEARCH DESIGN AND METHODS: Twenty-one subjects with hypertension and AER between 10 and 200 microg/min were randomized to receive either 50 mg losartan daily (n = 11) or placebo (n = 10). Drug therapy was given in two 4-week phases, separated by a 4-week washout period. In the last 2 weeks of each phase, patients were assigned to regular- or low-sodium diets in random order. Parameters measured at week 0 and 4 of each phase included plasma TGF-beta concentration, TGF-beta urinary excretion, AER, clinic mean arterial blood pressure, and urinary sodium excretion. RESULTS: Plasma TGF-beta was unaffected by losartan treatment or sodium intake. In the losartan group, urinary TGF-beta excretion decreased by 23.2% (-39.2 and 13.6) [median (interquartile range)] and 38.5% (-46.8 and -6.1) in the regular- and low-sodium phases, respectively (P < 0.05 for drug effect). In the placebo group, median changes of 0.0% (-12.1 and 44.4) and 0.0% (-29.2 and 110.7) occurred in the regular- and low-sodium phases, respectively. Sodium restriction did not affect urinary TGF-beta excretion in either losartan- or placebo-treated patients (P = 0.54 for overall dietary effect), and there was no evidence of interaction between drug and diet (P = 0.29). CONCLUSIONS: In hypertensive type 2 diabetic patients with elevated AER, the ARB losartan, but not sodium restriction, reduced urinary TGF-beta excretion. These data suggest that the renoprotective effects of losartan in patients with type 2 diabetes and nephropathy may include a reduction in renal TGF-beta production.


Assuntos
Albuminúria , Antagonistas de Receptores de Angiotensina , Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 2/urina , Dieta Hipossódica , Hipertensão/urina , Losartan/uso terapêutico , Sódio/urina , Fator de Crescimento Transformador beta/urina , Análise de Variância , Pressão Sanguínea , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/urina , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipertensão/sangue , Masculino , Pessoa de Meia-Idade , Placebos , Análise de Regressão
18.
Diabetes Care ; 25(4): 663-71, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11919122

RESUMO

OBJECTIVE: Diabetic subjects have a high prevalence of hypertension, increased total body exchangeable sodium levels, and an impaired ability to excrete a sodium load. This study assessed the effect of dietary sodium restriction on the efficacy of losartan in hypertensive subjects with type 2 diabetes and albumin excretion rates of 10-200 microg/min. RESEARCH DESIGN AND METHODS: In this study, 20 subjects were randomized to losartan 50 mg/day (n = 10) or placebo (n = 10). Drug therapy was given in two 4-week phases separated by a washout period. In the last 2 weeks of each phase, patients were assigned to low- or regular-sodium diets, in random order. In each phase, 24-h ambulatory blood pressure, urinary albumin-to-creatinine ratio (ACR), and renal hemodynamics were measured. RESULTS: Achieved urinary sodium on a low-sodium diet was 85 +/- 14 and 80 +/- 22 mmol/day in the losartan and placebo groups, respectively. In the losartan group, the additional blood pressure-lowering effects of a low-sodium diet compared with a regular-sodium diet for 24-h systolic, diastolic, and mean arterial blood pressures were 9.7 mmHg (95% confidence interval [CI], 2.2-17.2; P = 0.002), 5.5 mmHg (2.6-8.4; P = 0.002), and 7.3 mmHg (3.3- 11.3; P = 0.003), respectively. In the losartan group, the ACR decreased significantly on a low-sodium diet versus on a regular-sodium diet (-29% [CI -50.0 to -8.5%] vs. + 14% [-19.4 to 47.9%], respectively; P = 0.02). There was a strong correlation between fall in blood pressure and percent reduction in the ACR (r = 0.7, P = 0.02). In the placebo group, there were no significant changes in blood pressure or ACR between regular- and low-sodium diets. There were no significant changes in renal hemodynamics in either group. CONCLUSIONS: These data demonstrated that a low-sodium diet potentiates the antihypertensive and antiproteinuric effects of losartan in type 2 diabetes. The blood pressure reduction resulting from the addition of a low-sodium diet to losartan was of similar magnitude to that predicted from the addition of a second antihypertensive agent.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hipossódica , Hemodinâmica/fisiologia , Losartan/uso terapêutico , Albuminúria , Aldosterona/sangue , Angiotensina II/metabolismo , Glicemia/metabolismo , Creatinina/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Sinergismo Farmacológico , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Circulação Renal/efeitos dos fármacos , Circulação Renal/fisiologia , Renina/sangue , Sódio/urina
19.
Am J Kidney Dis ; 39(6): 1183-9, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12046029

RESUMO

The aim of this study is to assess the effects of age on (1) the ability of a spot albumin-creatinine ratio (ACR) to accurately predict 24-hour albumin excretion rate (AER), and (2) the performance of spot ACR as a screening test for microalbuminuria. Three hundred fourteen patients with diabetes aged 18 to 84 years attending a tertiary outpatient clinic underwent one 24-hour urine collection and, immediately after completion, provided one fasting spot morning urine sample. Twenty-four-hour AER and spot ACR were determined. Performance of spot ACR was assessed according to age and sex. Fifty-three percent of men and 32% of women had an AER of 20 microg/min or greater. Multiple regression analysis showed age was an independent predictor of spot ACR. For an AER of 20 microg/min for patients in the age range of 40 to 80 years, there was an increase in corresponding values for spot ACR from 18.2 mg/g (95% confidence interval [CI], 15.6 to 21.3) to 32.5 mg/g (95% CI, 27.5 to 38.4) in men and from 22.1 mg/g (95% CI, 18.0 to 27.1) to 56.4 mg/g (95% CI, 47.2 to 67.4) in women. Using ACR cutoff values of 22.1 mg/g or greater and 30.9 mg/g or greater in conventional units (equivalent to > or =2.5 and > or =3.5 mg/mmol in SI units) in men and women, the spot ACR provided high sensitivities (men, 95.7%; women, 93.35%) and had excellent receiver operator characteristic curves, respectively. However, the spot ACR false-positive rate increased with age from 15.9% (age, 40 to 65 years) to 31.8% (>65 years) in men and from 10.5% (age, 45 to 65 years) to 28.3% (>65 years) in women. Spot ACR is a good screening test for microalbuminuria, but a poor predictor of quantitative AER, and should not be used as a diagnostic test. The increase in spot ACR relative to 24-hour AER with age supports the use of sex- and age-adjusted ACR cutoff values.


Assuntos
Albuminúria/diagnóstico , Albuminúria/urina , Creatinina/urina , Nefropatias Diabéticas/diagnóstico , Programas de Rastreamento/normas , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Nefropatias Diabéticas/urina , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Curva ROC , Análise de Regressão , Sensibilidade e Especificidade , Fatores Sexuais
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