RESUMO
Primary aldosteronism (PA) is a group of disorders in which aldosterone is excessively produced. These disorders can lead to hypertension, hypokalemia, hypervolemia and metabolic alkalosis. The prevalence of PA ranges from 5% to 12% around the globe, and the most common causes are adrenal adenoma and adrenal hyperplasia. The importance of PA recognition arises from the fact that it can have a remarkably adverse cardiovascular and renal impact, which can even result in death. The aldosterone-to-renin ratio (ARR) is the election test for screening PA, and one of the confirmatory tests, such as oral sodium loading (OSL) or saline infusion test (SIT), is in general necessary to confirm the diagnosis. The distinction between adrenal hyperplasia (AH) or aldosterone-producing adenoma (APA) is essential to select the appropriate treatment. Therefore, in order to identify the subtype of PA, imaging exams such as computed tomography or magnetic ressonance imaging, and/or invasive investigation such as adrenal catheterization must be performed. According to the subtype of PA, optimal treatment - surgical for APA or pharmacological for AH, with drugs like spironolactone and amiloride - must be offered.
Assuntos
Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , HumanosRESUMO
BACKGROUND: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation seems to correct the overdiagnosis of chronic kidney disease (CKD) provided by Modification of Diet in Renal Disease (MDRD) equation. However, this point has not been tested in some ethnic groups. This study investigated the performance of MDRD and CKD-EPI equations in South Brazilian individuals. METHODS: This cross-sectional study included 354 individuals including healthy volunteers, diabetic and non-diabetic individuals with or without CKD. Glomerular filtration rate (GFR) was measured by the 51Cr-EDTA single-injection method (51Cr-GFR). Accuracy (P30), bias, and Bland-Altman agreement plots were evaluated. RESULTS: In the group as a whole, 51Cr-GFR was 87±37 (6-187), CKD-EPI eGFR, 82±30 (6-152), and MDRD eGFR, 77±28 (6-156) mL/min/1.73 m2 (p<0.001 for all comparisons). Analyzing the subset of individuals with 51Cr-GFR <60 mL/min/1.73 m2, P30 values were, respectively, 76% and 84% for MDRD and for CKD-EPI (p<0.001) while for 51Cr-GFR ≥60 mL/min/1.73 m2, P30 values were 57.5% for both equations (p=1.000). For MDRD and CKD-EPI, mean bias were negative for GFRs <60 (-11 vs. -12, p=0.221) and positive for values >60 (16 vs. 9, p<0.001). In multivariate analysis, absolute bias was unfavorably influenced by measured GFR >60 (for MDRD) and being diabetic or younger (for CKD-EPI). CONCLUSIONS: CKD-EPI reduces GFR underestimation in individuals with GFRs >60, but still presents a quite low accuracy at this GFR range. Moreover, it tends to overestimate GFR in subjects with GFRs <60 mL/min/1.73 m2. CKD stages 1 and 2, diabetes and young age had a negative influence on the performance of the equations.
Assuntos
Algoritmos , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Radioisótopos de Cromo/química , Creatinina/sangue , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Índice de Gravidade de Doença , Adulto JovemRESUMO
The association of hypertension and diabetes mellitus is extremely common, increasing the mortality risk of patients, mainly by cardiovascular causes. Regarding the blood pressure (BP) targets to be achieved, most guidelines suggest levels of 130âmmHg for SBP and of 80âmmHg for DBP. Dietary modifications are quite effective, and many studies suggest that decreasing sodium intake and increasing potassium ingestion are both valuable practices for reducing BP. This can be achieved by stimulating the ingestion of lacteous products, vegetables, and nuts. As for the ideal pharmacologic treatment for hypertension, either calcium channel blockers, diuretics or angiotensin-system blockers can be the first class of drug to be used. In this review, we summarize the evaluation of patients with diabetes mellitus and hypertension, and discuss the available therapeutic approaches, with emphasis on evidence-based dietary recommendations.
Assuntos
Diabetes Mellitus , Hipertensão , Hipotensão , Humanos , Dieta , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pressão SanguíneaRESUMO
INTRODUCTION: New antihyperglycemic medications have been proven to have cardiovascular (CV) and renal benefits in type 2 diabetes mellitus (T2DM); however, an evidence-based decision tree in specific clinical scenarios is lacking. MATERIALS AND METHODS: Systematic review and meta-analysis of randomized controlled trials (RCTs), with trial sequential analysis (TSA). Randomized controlled trial inclusion criteria were patients with T2DM from 1 of these subgroups: elderly, obese, previous atherosclerotic CV disease (ASCVD), previous coronary heart disease (CHD), previous heart failure (HF), or previous chronic kidney disease (CKD). Randomized controlled trials describing those subgroups with at least 48 weeks of follow-up were included. Outcomes: 3-point major adverse cardiovascular events (MACE), CV death, hospitalization due to HF, and renal outcomes. We performed direct meta-analysis with the number of events in the intervention and control groups in each subset, and the relative risk of the events was calculated. RESULTS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) were the only antihyperglycemic agents related to a reduction in CV events in different populations. For obese and elderly populations, GLP-1 RA were associated with benefits in 3-point MACE; for patients with ASCVD, both SGLT2i and GLP-1 RA had benefits in 3-point MACE, while for patients with CHD, only SGLT2i were beneficial. CONCLUSIONS: SGLT2i and GLP-1 RA reduced CV events in selected populations: SGLT2i led to a reduction in events in patients with previous CHD, ASCVD, and HF. GLP-1 RA led to a reduction in CV events in patients with ASCVD, elderly patients, and patients with obesity. Trial sequential analysis shows that these findings are conclusive. This review opens a pathway towards evidence-based, personalized treatment of T2DM. REGISTRATION: PROSPERO CRD42019132807.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Incretinas/uso terapêutico , Assistência Centrada no Paciente , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Gerenciamento Clínico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY-X). METHODS: We conducted a next-generation sequencing target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected, of which 26 had an initial clinical suspicion of MODY-GCK and 76 were non-GCK MODY. RESULTS: After excluding all benign and likely benign variants and variants of uncertain significance, we were able to assign a genetic cause for 12.7% (13/102) of the probands. Three rare MODY subtypes were identified (PDX1/NEUROD1/ABCC8), and eight variants had not been previously described/mapped in genomic databases. Important clinical findings were evidenced in some cases after genetic diagnosis, such as MODY-PDX1/HNF1B. CONCLUSION: A multiloci genetic approach allowed the identification of rare MODY subtypes, reducing the large percentage of MODY-X in Brazilian cases and contributing to a better clinical, therapeutic, and prognostic characterization of these rare phenotypes.
Assuntos
Diabetes Mellitus Tipo 2/genética , Testes Genéticos/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Adulto , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Brasil , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Proteínas de Homeodomínio/genética , Humanos , Masculino , Análise de Sequência de DNA , Receptores de Sulfonilureias/genética , Transativadores/genética , Adulto JovemRESUMO
Objective Our objective was to evaluate gestational weight gain (GWG) patterns and their relation to birth weight. Subjects and methods We prospectively enrolled 474 women with gestational diabetes mellitus (GDM) at a university hospital (Porto Alegre, Brazil, November 2009-May 2015). GWG was categorized according to the 2009 Institute of Medicine guidelines; birth weight was classified as large (LGA) or small (SGA) for gestational age. Adjusted relative risks (aRRs) and 95% confidence intervals (95% CIs) were determined. Results Adequate GWG occurred in 121 women [25.5%, 95% CI: 22, 30%]; excessive, in 180 [38.0%, 95% CI: 34, 43%]; and insufficient, in 173 [36.5%, 95% CI: 32, 41%]. In women with normal body mass index (BMI), the prevalence of SGA was higher in those with insufficient compared to adequate GWG (30% vs. 0%, p < 0.001). In women with BMI ≥ 25 kg/m2, excessive GWG increased the prevalence of LGA [aRR 2.58, 95% CI: 1.06, 6.29] and protected from SGA [aRR 0.25, 95% CI: 0.10, 0.64]. Insufficient vs. adequate GWG did not influence the prevalence of SGA [aRR 0.61, 95% CI: 0.31, 1.22]; insufficient vs. excessive GWG protected from LGA [aRR 0.46, 95% CI: 0.23, 0.91]. Conclusions One quarter of this cohort achieved adequate GWG, indicating that specific ranges have to be tailored for GDM. To prevent inadequate birth weight, excessive GWG in women with higher BMI and less than recommended GWG in normal BMI women should be avoided; less than recommended GWG may be suitable for overweight and obese women.
Assuntos
Peso ao Nascer/fisiologia , Diabetes Gestacional/fisiopatologia , Aumento de Peso/fisiologia , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos , Fatores SocioeconômicosRESUMO
Aspirin is recommended as cardiovascular disease prevention in patients with diabetes mellitus. Due to the increased risk of bleeding and because of the hypothesis that there could be a worsening of microvascular complications related to aspirin, there has been observed an important underutilization of the drug. However, it is now known that aspirin is not associated with a deleterious effect on diabetic retinopathy and there is evidence indicating that it also does not affect renal function with usual doses (150 mg/d). On the other hand, higher doses may prove necessary, since recent data suggest that diabetic patients present the so called "aspirin resistance". The mechanisms of this resistance are not yet fully understood, being probably related to an abnormal intrinsic platelet activity. The employment of alternative antiplatelet strategies or the administration of higher aspirin doses (150-300 mg/d) should be better evaluated regarding effective cardiovascular disease prevention in diabetes as well as the possible effects on microvascular complications.
Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/fisiopatologia , Inibidores da Agregação Plaquetária/administração & dosagem , Aspirina/efeitos adversos , Ensaios Clínicos como Assunto , Angiopatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/prevenção & controle , Retinopatia Diabética/prevenção & controle , Humanos , Metanálise como Assunto , Inibidores da Agregação Plaquetária/efeitos adversos , Prevenção PrimáriaRESUMO
AIMS: Maturity-Onset Diabetes of the Young (MODY) comprises a heterogeneous group of monogenic forms of diabetes caused by mutations in at least 14 genes, but mostly by mutations in Glucokinase (GCK) and hepatocyte nuclear factor-1 homeobox A (HNF1A). This study aims to establish a national registry of MODY cases in Brazilian patients, assessing published and unpublished data. METHODS: 311 patients with clinical characteristics of MODY were analyzed, with unpublished data on 298 individuals described in 12 previous publications and 13 newly described cases in this report. RESULTS: 72 individuals had GCK mutations, 9 described in Brazilian individuals for the first time. One previously unpublished novel GCK mutation, Gly178Ala, was found in one family. 31 individuals had HNF1A mutations, 2 described for the first time in Brazilian individuals. Comparisons of GCK probands vs HNF1A: age 16±11 vs 35±20years; age at diagnosis 11±8 vs 21±7years; BMI 19±6 vs 25±6kg/m2; sulfonylurea users 5 vs 83%; insulin users 5 vs 17%; presence of arterial hypertension 0 vs. 33%, all p<0.05. No differences were observed in lipids and C-peptide. CONCLUSIONS: Most MODY cases in Brazil are due to GCK mutations. In agreement with other studied populations, novel mutations are common. Only 14% of patients with familial diabetes carry a HNF1A mutation. Diagnosis of other rare forms of MODY is still a challenge in Brazilian population, as well as adequate strategies to screen individuals for molecular diagnosis.
Assuntos
Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Adolescente , Adulto , Brasil , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Masculino , Sistema de Registros , Adulto JovemRESUMO
Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects approximately 40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE >20 microg/min and < or =199 microg/min) and macroalbuminuria (UAE > or =200 microg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c <7%), treating hypertension (<130/80 mmHg or <125/75 mmHg if proteinuria >1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol <100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.
Assuntos
Nefropatias Diabéticas/terapia , Albuminúria , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/prevenção & controle , Dieta com Restrição de Proteínas , Humanos , Monitorização FisiológicaRESUMO
Thirty-two patients with diabetes negative for point mutations in GCK and HNF1A underwent further molecular screening of GCK, HNF1A, HNF4A, and HNF1B by MLPA analysis. We described the first Brazilian case of MODY5 due to a heterozygous whole-gene deletion in HNF1B, who developed rapidly progressive renal failure and death.
Assuntos
Diabetes Mellitus Tipo 2/genética , Deleção de Genes , Fator 1-beta Nuclear de Hepatócito/genética , Adulto , Brasil , Estudos de Casos e Controles , Doenças do Sistema Nervoso Central , Esmalte Dentário/anormalidades , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Glucoquinase/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Heterozigoto , Humanos , Achados Incidentais , Doenças Renais Císticas , Masculino , FenótipoRESUMO
Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM", who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre - Rio Grande do Sul, Brazil.
Assuntos
Separação Celular/métodos , Diabetes Mellitus Tipo 1/terapia , Arquitetura de Instituições de Saúde/normas , Transplante das Ilhotas Pancreáticas/tendências , Ilhotas Pancreáticas , Brasil , Humanos , Insulina/uso terapêutico , Transplante das Ilhotas Pancreáticas/economia , Transplante das Ilhotas Pancreáticas/legislação & jurisprudência , Laboratórios/organização & administraçãoAssuntos
Meios de Contraste/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Nefropatias/prevenção & controle , Metformina/uso terapêutico , Contraindicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipoglicemiantes/farmacocinética , Nefropatias/induzido quimicamente , Masculino , Metformina/farmacocinéticaRESUMO
BACKGROUND: Vitamin D deficiency in pregnancy has been associated with an increased risk of preeclampsia. However, the association between serum vitamin D and blood pressure in pregnant women has been scarcely evaluated, particularly in women with a high risk of developing hypertensive disorders of pregnancy. We sought to evaluate the association between serum 25-hydroxyvitamin D and blood pressure in pregnant women with gestational diabetes mellitus (GDM). METHODS: A cohort of 184 pregnant women with GDM was followed during the third trimester of pregnancy and early puerperium. Blood pressure was recorded in all prenatal visits, and serum vitamin D was measured by chemiluminescence immunoassay. Pearson's coefficients and multiple linear regressions were used to study predictors of blood pressure levels. RESULTS: Women with vitamin D insufficiency (<30ng/mL; n = 159) had higher systolic and diastolic blood pressure than the remaining participants. In white women (n = 136), serum vitamin D levels presented a significant negative correlation with systolic blood pressure at the beginning (r = -0.268; P = 0.002) and at the end of the third trimester (r = -0.203; P = 0.02), and vitamin D significantly affected systolic blood pressure after adjusting for confounders. This was not observed in women of other ethnicities. CONCLUSIONS: In this cohort of pregnant women with GDM, vitamin D insufficiency was associated with higher blood pressure, and in white women, serum vitamin D was an independent predictor of systolic blood pressure during pregnancy.
Assuntos
Pressão Sanguínea , Diabetes Gestacional/epidemiologia , Hipertensão Induzida pela Gravidez/sangue , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Brasil/epidemiologia , Estudos de Coortes , Diástole , Feminino , Humanos , Hipertensão Induzida pela Gravidez/epidemiologia , Modelos Lineares , Gravidez , Terceiro Trimestre da Gravidez , Fatores de Risco , Sístole , Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , População BrancaRESUMO
Thirty-two Brazilian families with MODY phenotype were screened for GCK and HNF1A mutations. GCK mutations were found in 8 families, all patients with mild asymptomatic hyperglycaemia; 3 of them are novel: p.Asp365Asn, p.Gly81Asp and p.Val253Leu. Previously described mutations in HNF1A were found in 2 families.
Assuntos
DNA/genética , Diabetes Mellitus Tipo 2/genética , Glucoquinase/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Mutação de Sentido Incorreto , Adolescente , Adulto , Brasil/epidemiologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Glucoquinase/metabolismo , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Hiperglicemia/genética , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Adulto JovemRESUMO
ABSTRACT Objective Our objective was to evaluate gestational weight gain (GWG) patterns and their relation to birth weight. Subjects and methods We prospectively enrolled 474 women with gestational diabetes mellitus (GDM) at a university hospital (Porto Alegre, Brazil, November 2009-May 2015). GWG was categorized according to the 2009 Institute of Medicine guidelines; birth weight was classified as large (LGA) or small (SGA) for gestational age. Adjusted relative risks (aRRs) and 95% confidence intervals (95% CIs) were determined. Results Adequate GWG occurred in 121 women [25.5%, 95% CI: 22, 30%]; excessive, in 180 [38.0%, 95% CI: 34, 43%]; and insufficient, in 173 [36.5%, 95% CI: 32, 41%]. In women with normal body mass index (BMI), the prevalence of SGA was higher in those with insufficient compared to adequate GWG (30% vs. 0%, p < 0.001). In women with BMI ≥ 25 kg/m2, excessive GWG increased the prevalence of LGA [aRR 2.58, 95% CI: 1.06, 6.29] and protected from SGA [aRR 0.25, 95% CI: 0.10, 0.64]. Insufficient vs. adequate GWG did not influence the prevalence of SGA [aRR 0.61, 95% CI: 0.31, 1.22]; insufficient vs. excessive GWG protected from LGA [aRR 0.46, 95% CI: 0.23, 0.91]. Conclusions One quarter of this cohort achieved adequate GWG, indicating that specific ranges have to be tailored for GDM. To prevent inadequate birth weight, excessive GWG in women with higher BMI and less than recommended GWG in normal BMI women should be avoided; less than recommended GWG may be suitable for overweight and obese women.
Assuntos
Humanos , Feminino , Gravidez , Recém-Nascido , Adulto , Peso ao Nascer/fisiologia , Aumento de Peso/fisiologia , Diabetes Gestacional/fisiopatologia , Fatores Socioeconômicos , Estudos ProspectivosRESUMO
OBJECTIVE To evaluate the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate (GFR) in type 2 diabetic patients with GFR >60 mL/min/1.73 m(2). RESEARCH DESIGN AND METHODS This was a cross-sectional study including 105 type 2 diabetic patients. GFR was measured by (51)Cr-EDTA method and estimated by the MDRD and CKD-EPI equations. Serum creatinine was measured by the traceable Jaffe method. Bland-Altman plots were used. Bias, accuracy (P30), and precision were evaluated. RESULTS The mean age of patients was 57 ± 8 years; 53 (50%) were men and 90 (86%) were white. Forty-six (44%) patients had microalbuminuria, and 14 (13%) had macroalbuminuria. (51)Cr-EDTA GFR was 103 ± 23, CKD-EPI GFR was 83 ± 15, and MDRD-GFR was 78 ± 17 mL/min/1.73 m² (P < 0.001). Accuracy (95% CI) was 67% (58-74) for CKD-EPI and 64% (56-75) for MDRD. Precision was 21 and 22, respectively. CONCLUSIONS The CKD-EPI and MDRD equations pronouncedly underestimated GFR in type 2 diabetic patients.