Proteinúria ainda é útil para triagem e diagnóstico de nefropatia diabética sintomática

OBJECTIVE: To assess the performance of urinary total protein measurements intimed 24-h urine collection and in a diurnal random urine specimen for the screeningand diagnosis of overt diabetic nephropathy.PATIENTS AND METHODS: A total of 167 diabetic patients (20 type 1 and 147 type2 diabetic patients; 78 women and 89 men), aged 20-84 years, collected 217 timed24-h urine specimens. Albumin was measured by immunoturbidimetry, total proteinby the sulfosalicylic acid technique, and creatinine by Jaffé’s method. According tothe timed 24-h urinary albumin excretion rate, samples were divided into three groups:normoalbuminuric (urinary albumin excretion rate < 20 mg/min; n = 84),microalbuminuric (urinary albumin excretion rate 20-200 mg/min; n = 78), andmacroalbuminuric (urinary albumin excretion rate > 200 mg/min; n = 55). Eight-sixpatients also collected 105 random urine specimens (normoalbuminuric, n = 47;microalbuminuric, n = 37; macroalbuminuric, n = 21), and urinary protein concentrationand urinary protein-to-creatinine ratio were measured. The receiver operatingcharacteristics curve approach was used to analyze the performance of the diagnostictests.RESULTS: Spearman’s coefficient of correlation of 24-h urinary albumin excretionrate versus 24-h urinary protein was 0.95 ( P < 0.001), and of 24-h urinary albuminexcretion rate versus urinary protein concentration and urinary protein-to-creatinineratio were 0.77 and 0.72, respectively (P < 0.001). The calculated areas (±SEM)under the receiver operating characteristics curve for the diagnosis of overt diabeticnephropathy were 0.9987 ± 0.001 for 24-h urinary protein, 0.9926 ± 0.006 for urinaryprotein concentration, and 0.9751 ± 0.014 for urinary protein-to-creatinine ratio. Inthe receiver operating characteristics curves, the first points with 100% sensivitywere 541 mg (95.7% specificity) for 24-h urinary protein, 431 mg/l (92.9% specificity)for urinary protein concentration, and 0.2 (76.2% specificity) for urinary protein-tocreatinine ratio.CONCLUSIONS: Measurements of proteinuria presented almost perfect accuracyfor the screening and diagnosis of overt diabetic nephropathy. Protein measurementin spot urine is a reliable and simple method for the screening and diagnosis of overtdiabetic nephropathy.OBJETIVO: Avaliar a utilização de medições de proteína urinária total em coletasurinárias de 24 horas e em amostras diurnas coletadas aleatoriamente para triageme diagnóstico de nefropatia diabética sintomática. PACIENTES E MÉTODOS: Foram coletadas 217 amostras de urina a cada 24 h deum total de 167 pacientes diabéticos (20 pacientes com diabetes tipo 1 e 147 comdiabetes tipo 2; 78 mulheres e 89 homens), com idade entre 20 e 84 anos. A albuminafoi medida por imunoturbidimetria, a proteína urinário total foi medida pela técnicado ácido sulfosalicílico e a creatinina, pelo método de Jaffe. As amostras foramdivididas em três grupos de acordo com a taxa de 24 h de excreção urinária dealbumina: normoalbuminúricos (taxa de excreção urinária de albumina < 20 mg/min;n=84), microalbuminúricos (taxa de excreção urinária de albumina 20-200 mg/min;n=78), e macroalbuminúricos (taxa de excreção urinária de albumina > 200 mg/min;n=55). Foram coletadas ainda 105 amostras aleatórias de urina de 86 pacientes(normoalbuminúricos, n=47; microalbuminúricos, n=37; macroalbuminúricos, n=21),das quais a concentração urinária de proteina e a relação proteína/creatinina urináriaforam obtidas. O método da curva de características operacionais do receptor foiutilizado para analisar o desempenho dos testes diagnósticos.RESULTADOS: O coeficiente de correlação de Spearman para a comparação entrea taxa de 24 h de excreção urinária de albumina e a proteina urinária de 24 h foi 0,95(P < 0,001). O mesmo coeficiente, para a comparação da taxa de 24 h de excreçãourinária de albumina com a concentração urinária de proteina, assim como com arelação proteína/creatinina urinária foi 0,77 e 0,72, respectivamente (P < 0,001). Asáreas calculadas (+ erro padrão) abaixo da curva de características operacionais doreceptor para o diagnóstico de nefropatia diabética sintomática foram: 0,9987 + 0,001para a proteina urinária de 24 h; 0,9926 + 0,006 para concentração urinária deproteína; e 0,9751 + 0,014 para a relação proteina/creatinina urinária. Nas curvasde características operacionais do receptor os primeiros pontos com 100% desensitividade foram: 541mg (95,7% de especificidade) para proteína urinária de 24h, 431 mg/l (92,9% de especificidade) para concentração urinária, e 0,2 (76,2% deespecificidade) para a relação proteína/creatinina urinária.CONCLUSÕES: As medidas de proteinuria foram extremamente eficazes na triageme no diagnóstico de nefropatia diabética sintomática. A medição de proteína urináriaé um método confiável e simples para a triagem e diagnóstico de nefropatia diabéticasintomátic

A hiperfiltração glomerular está associada a alterações de pressão sangüínea em pacientes DMDI normotensivos

OBJECTIVE: To analyze the blood pressure patterns in normoalbuminuric IDDM patients with glomerular hyperfiltration. PATIENTS AND METHODS: A controlled cross-sectional study of 38 normotensive normoalbuminuric (urinary albumin excretion rate <20 mg/min) IDDM patients (18 hyperfiltering [glomerular filtration rate > 134 ml × min-1× 1.73m-2] and 20 normofiltering) and 20 normal individuals matched for age, sex, and body mass index was performed. The 24-h ambulatory blood pressure was monitored using an auscultatory technique; the glomerular filtration rate was measured by 51Cr-labeled EDTA method; extracellular volume by the distribution volume of 51Cr-labeled EDTA; and 24-h urinary albumin excretion rate by radioimmunoassay. RESULTS: Mean nocturnal diastolic blood pressure was higher in hyperfiltering IDDM patients (70.4 ± 7.8 mmHg), when compared with the control group (65.1 ± 5.3 mmHg, P = 0.04). Diastolic blood pressure night:day ratio was higher in hyperfiltering IDDM patients (92.0 ± 8.6%), when compared with normofiltering IDDM patients (85.9 ± 4.8%) and control subjects (87.0 ± 6.8%, P = 0.02). In IDDM patients, the glomerular filtration rate significantly correlated with the diastolic blood pressure night:day ratio (r = 0.5, P = 0.002), extracellular volume (r = 0.4, P = 0.002), and HbA1 (r = 0.3, P = 0.03). In stepwise multiple regression analysis, factors associated with glomerular filtration rate were diastolic blood pressure night:day ratio, extracellular volume, and HbA1 (adjusted r 2 = 0.27, P = 0.003). CONCLUSIONS: Glomerular hyperfiltration is associated with higher nocturnal diastolic blood pressure and with a blunted nocturnal decrease in diastolic blood pressure levels in normotensive and normoalbuminuric IDDM patientsOBJETIVO: Analisar os padrões de pressão sangüínea em pacientes normoalbuminúricos DMDI com hiperfiltração glomerular.PACIENTES E MÉTODOS: Foi feito um estudo controlado em cortes transversais com 38 pacientes normoalbuminúricos normotensivos (taxa deexcreção urinária de albumina>20 mg/min) DMDI (hiperfiltração em 18 [taxade filtração glomerular>134 ml x min-1 x 1,73m-2] e normofiltração em 20), e de20 indivíduos normais agrupados por idade, sexo, e índice de massa corporal.A pressão sangüínea ambulatorial foi monitorada em 24 h pelo método auscultatório; a taxa de filtração glomerular foi medida através do método51Cr-EDTA; o volume extracelular, através do volume de distribuição do 51CrEDTA; e a taxa excreção urinária de albumina em 24 h, por radioimunoensaio.RESULTADOS: A média da pressão sangüinea diastólica noturna foi mais alta em pacientes DMDI com hiperfiltração (70,4 + 7,8 mmHg), quando comparada à do grupo controle (65,1 + 5,3 mmHg, P=0,04). A relaçãodiurna:noturna da pressão sangüínea diastólica foi mais alta em pacientes DMDI com hiperfiltração (92,0 + 8,6%) quando comparada a mesma relação dos pacientes DMDI com normofiltração (85,9 + 4,8%) e controles (87,0 + 6,8%, P=0,02). Os pacientes DMDI apresentaram uma taxa de filtração glomerular significativamente correlacionada com a relação diurna:noturnade pressão diastólica (r=0,5, P=0,002), com o volume extracelular (r=0,4, P=0,002), e com HbA1 (r=0,3, P=0,03). Na análise de regressão múltiplaescalonada, os fatores associados com a taxa de filtração glomerular foram: relação diurna:noturna de pressão sangüinea diastólica, volume extracelular, e HbA1 (ajustado r2=0,27, P=0,003). CONCLUSÕES: Hiperfiltração glomerular está associada à pressão sangüínea diastólica noturna elevada e a uma diminuição noturna abrupta dos níveis de pressão sangüínea diastólica em pacientes normotensivos eem pacientes DMDI normoalbuminúricos.

DIABETE MELITO: DIAGNÓSTICO, CLASSIFICAÇÃO E AVALIAÇÃO DO CONTROLE GLICÊMICO

Diabetes mellitus and other categories of impaired glucose tolerance are frequent in the adult population and are associated with an increased risk for cardiovascular disease and microvascular complications. The diagnosis of these entities should be performed early and using sensitive and accurate methods, since lifestyle changes and correction of hyperglycemia may delay the incidence of diabetes and its complications. Glucose tolerance test is the reference method and the diagnosis of diabetes and impaired glucose tolerance are established when the 2 h plasma glucose after the oral intake of 75 g of glucose is ≥ 200 mg/dl or ≥ 140and < 200 mg/dl, respectively. When it is not possible to perform this test, fasting plasma glucose levels ≥ 126 mg/dl or ≥ 110 and < 126 mg/dl, respectively, are used to establish the diagnosis of diabetes and impaired fasting plasma glucose. Glycohemoglobin should not be used for the diagnosis but it is the reference method for evaluation of the long term glucose control. The etiological classification of diabetes mellitus includes 4 categories: type 1 diabetes, type 2 diabetes, other specific types of diabetes and gestational diabetes. The assignment of the patient in each category usually is made on clinical grounds, however in some case could be necessary the measurement of C-peptide and auto antibodies. Diabete e alterações da tolerância à glicose são freqüentes na população adulta e estão associados a um aumento da mortalidade por doença cardiovascular e complicações microvasculares. O diagnóstico destas situações deve ser feito precocemente, utilizando métodos sensíveis e acurados, já que mudanças no estilo de vida e a correção da hiperglicemia podem retardar o aparecimento do diabete ou de suas complicações. O teste oral de tolerância à glicose é o método de referência, considerando-se a presença de diabete ou tolerância à glicose diminuída quando a glicose plasmática de 2 h após a ingestão de 75 g de glicose for≥ 200 mg/dl ou ≥ 140 e < 200 mg/dl, respectivamente. Quando este teste não puder ser realizado, utiliza-se a medida da glicose plasmática em jejum, considerando-se como diabete ou glicose alterada em jejum quando os valores forem ≥ 126 mg/dl ou ≥ 110 e < 126 mg/dl, respectivamente. A medida da glico-hemoglobina não deve ser utilizada para o diagnóstico, mas é o método de referência para avaliar o grau de controle glicêmico a longo prazo. A classificação etiológica proposta atualmente para o diabete melito inclui 4 categorias: diabete melito tipo 1, diabete melito tipo 2, outros tipos específicos de diabete e diabete gestacional. A classificação do paciente é usualmente feita em bases clínicas, mas a medida de autoanticorpos e do peptídeo C pode ser útil em alguns casos

Poor glycaemic control in Brazilian patients with type 2 diabetes attending the public healthcare system a cross-sectional study

Objectives: To describe the clinical profile of Brazilian patients with type 2 diabetes attending the public healthcare system and identify factors associated with poor glycaemic control.Design: Cross-sectional study.Setting: 14 centres in five regions of Brazil, including primary care units and outpatient clinics of University Hospitals.Participants: Patients with type 2 diabetes attending outpatient clinics of public healthcare system.Main outcome measured: Glycated haemoglobin (HbA1c), centrally measured by high-performance liquid chromatography (National Glycohemoglobin Standardization Program certified).Results: A total of 5750 patients aged 61 10 years, with 11 8 years of diabetes duration (66% women, 56% nonwhite, body mass index: 28.0 5.3 kg/m(2)) were analysed. Mean HbA1c was 8.6 +/- 2.2%, and median HbA1c was 8.1% (6.9% to 9.9%). HbA1c 8%.Conclusions: the majority of Brazilian patients with type 2 diabetes attending the public healthcare system had HbA1c levels above recommended targets. the recognition of Northeast residents and non-white patients as vulnerable populations should guide future policies and actions to prevent and control diabetes.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundo de Incentivo a Pesquisa (FIPE) of Hospital de Clinicas de Porto Alegre (HCPA)Pfizer PharmaceuticalHosp Clin Porto Alegre, Endocrine Div, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Porto Alegre, RS, BrazilHosp Getulio Vargas, Endocrine Div, Manaus, Amazonas, BrazilUniv Fed Amazonas, Manaus, Amazonas, BrazilFed Univ Para, BR-66059 Belem, Para, BrazilUniversidade Federal de São Paulo, Endocrine Div, São Paulo, BrazilUniversidade Federal de São Paulo, Endocrine Div, São Paulo, BrazilWeb of Scienc

Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Oxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and require association with subunit p22phox (encoded by the <it>CYBA </it>gene). Increased expression of p22phox was described in animal models of diabetic nephropathy. In the opposite direction, glutathione is one of the main endogenous antioxidants whose plasmatic concentrations were reported to be reduced in diabetes patients. The aim of the present investigation was to test whether functional single nucleotide polymorphisms (SNPs) in genes involved in the generation of NADPH-dependent O₂^•-(-675 T → A in <it>CYBA</it>, unregistered) and in glutathione metabolism (-129 C → T in <it>GCLC </it>[rs17883901] and -65 T → C in <it>GPX3 </it>[rs8177412]) confer susceptibility to renal disease in type 1 diabetes patients.</p> <p>Methods</p> <p>401 patients were sorted into two groups according to the presence (n = 104) or absence (n = 196) of overt diabetic nephropathy or according to glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease (MDRD) equation: ≥ 60 mL (n = 265) or < 60 mL/min/1.73 m²(n = 136) and were genotyped.</p> <p>Results</p> <p>No differences were found in the frequency of genotypes between diabetic and non-diabetic subjects. The frequency of GFR < 60 mL/min was significantly lower in the group of patients carrying <it>CYBA </it>genotypes T/A+A/A (18.7%) than in the group carrying the T/T genotype (35.3%) (P = 0.0143) and the frequency of GFR < 60 mL/min was significantly higher in the group of patients carrying <it>GCLC </it>genotypes C/T+T/T (47.1%) than in the group carrying the C/C genotype (31.1%) (<it>p </it>= 0.0082). Logistic regression analysis identified the presence of at least one A allele of the <it>CYBA </it>SNP as an independent protection factor against decreased GFR (OR = 0.38, CI95% 0.14-0.88, <it>p </it>= 0.0354) and the presence of at least one T allele of the <it>GCLC </it>rs17883901 SNP as an independent risk factor for decreased GFR (OR = 2.40, CI95% 1.27-4.56, <it>p </it>= 0.0068).</p> <p>Conclusions</p> <p>The functional SNPs <it>CYBA </it>-675 T → A and <it>GCLC </it>rs17883901, probably associated with cellular redox imbalances, modulate the risk for renal disease in the studied population of type 1 diabetes patients and require validation in additional cohorts.</p

Teaching open and reproducible scholarship: a critical review of the evidence base for current pedagogical methods and their outcomes

In recent years, the scientific community has called for improvements in the credibility, robustness and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence student outcomes is needed. In this paper, we provide the first critical review of literature surrounding the integration of open and reproducible scholarship into teaching and learning and its associated outcomes in students. Our review highlighted how embedding open and reproducible scholarship appears to be associated with (i) students' scientific literacies (i.e. students’ understanding of open research, consumption of science and the development of transferable skills); (ii) student engagement (i.e. motivation and engagement with learning, collaboration and engagement in open research) and (iii) students' attitudes towards science (i.e. trust in science and confidence in research findings). However, our review also identified a need for more robust and rigorous methods within pedagogical research, including more interventional and experimental evaluations of teaching practice. We discuss implications for teaching and learning scholarship