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2.
Arq Bras Cardiol ; 113(4): 787-891, 2019 Nov 04.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31691761
3.
Mol Genet Genomic Med ; 7(12): e962, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31595705

RESUMO

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.

4.
Obes Rev ; 20(5): 633-647, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30821085

RESUMO

Bariatric surgery has shifted from being a risky procedure to an evidence-based one, with proven benefits on all-cause mortality, cardiovascular disease, cancer, and diabetes control. The procedure has an overall positive result on type 2 diabetes mellitus (T2DM), with a substantial number of patients achieving disease remission. This has resulted in several studies assessing possible weight-independent effects of bariatric surgery on glycemic improvement, in addition to recommendation of the procedure to patients with class 1 obesity and T2DM, for whom the procedure was classically not indicated, and adoption of a new term, "metabolic surgery," to highlight the overall metabolic benefit of the procedure beyond weight loss. Recently, the Diabetes Surgery Summit (DSS) has included metabolic surgery in its T2DM treatment algorithm. Although the discussion brought by this consensus is highly relevant, the recommendation of metabolic surgery for patients with uncontrolled T2DM and a body mass index of 30 to 35 kg/m2 still lacks enough evidence. This article provides an overall view of the metabolic benefits of bariatric/metabolic surgery in patients with class 1 obesity, compares the procedure against clinical treatment, and presents our rationale for defending caution on recommending the procedure to less obese individuals.

5.
Diabetes ; 68(5): 947-952, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30765337

RESUMO

Melatonin, a pineal hormone synthesized at night, is critical for the synchronization of circadian and seasonal rhythms, being a key regulator of energy metabolism in many animal species. Although studies in humans are lacking, several reports, mainly on hibernating animals, demonstrated that melatonin supplementation and a short photoperiod increase brown adipose tissue (BAT) mass. The present proof-of-concept study is the first, to our knowledge, to evaluate BAT in patients with melatonin deficiency (radiotherapy or surgical removal of pineal gland) before and after daily melatonin (3 mg) replacement for 3 months. All four studied patients presented increased BAT volume and activity measured by positron emission tomography-MRI. We also found an improvement in total cholesterol and triglyceride blood levels without significant effects on body weight, liver fat, and HDL and LDL levels. Albeit not statistically significant, fasting insulin levels and HOMA of insulin resistance decreased in all four patients. The present results show that oral melatonin replacement increases BAT volume and activity and improves blood lipid levels in patients with melatonin deficiency, suggesting that melatonin is a possible BAT activator. Future studies are warranted because hypomelatoninemia is usually present in aging and appears as a result of light-at-night exposure and/or the use of ß-blocker drugs.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Melatonina/farmacologia , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Masculino , Triglicerídeos/sangue
6.
J Clin Endocrinol Metab ; 103(8): 2807-2810, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29846625

RESUMO

Context: Acquired generalized lipodystrophy (AGL), a rare disorder characterized by loss of subcutaneous adipose tissue, is estimated to occur in association with autoimmune diseases in ~25% of the cases. Common variable immunodeficiency (CVI) is a condition known for its strong association with autoimmune diseases often occurring with negative autoantibodies. To the best of our knowledge, we describe the first known case of AGL in a patient with CVI. Case Description: A 24-year-old man was referred to our center with hyperglycemia, hypertriglyceridemia, hepatomegaly, and a clear pattern of generalized fat loss. AGL had been diagnosed on the basis of the clinical and laboratory findings. Because of the presence of associated hypogammaglobulinemia, a diagnosis of CVI was subsequently established. Conclusions: We propose that AGL be added to the list of possible diseases associated with CVI and, owing to the similar clinical presentation with type 1 diabetes mellitus, be included in the differential diagnosis of this condition, which is present in 1.5% of patients with CVI.


Assuntos
Imunodeficiência de Variável Comum/complicações , Lipodistrofia/etiologia , Adulto , Humanos , Hipertrigliceridemia/complicações , Hipertrigliceridemia/imunologia , Lipodistrofia/imunologia , Masculino , Adulto Jovem
8.
Expert Opin Drug Saf ; 16(1): 27-39, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27732121

RESUMO

INTRODUCTION: Few studies on combination therapies for the treatment of obesity had been conducted until recently, when two fixed-dose combinations, bupropion-naltrexone ER fixed-dose combination and phentermine-topiramate ER titrated-dose combinations were evaluated in clinical studies that ultimately led to FDA approval. Areas covered: In this review, we discuss safety concerns about both combinations, the rationale and history of combination therapies for obesity (including phentermine plus fenfluramine), and possible future new combinations. Expert opinion: Combination therapies are a promising new area in obesity treatment, similar to what occurs with diabetes and hypertension. Safety assessment is highly important due to the high number of potential users on a chronic basis.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Animais , Fármacos Antiobesidade/efeitos adversos , Fármacos Antiobesidade/uso terapêutico , Bupropiona/administração & dosagem , Bupropiona/efeitos adversos , Bupropiona/uso terapêutico , Preparações de Ação Retardada , Combinação de Medicamentos , Frutose/administração & dosagem , Frutose/efeitos adversos , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Naltrexona/administração & dosagem , Naltrexona/efeitos adversos , Naltrexona/uso terapêutico , Fentermina/administração & dosagem , Fentermina/efeitos adversos , Fentermina/uso terapêutico , Topiramato
12.
Expert Opin Drug Saf ; 14(2): 305-15, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25563411

RESUMO

INTRODUCTION: Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors. AREAS COVERED: This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo. EXPERT OPINION: Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin's selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.


Assuntos
Fármacos Antiobesidade/efeitos adversos , Benzazepinas/efeitos adversos , Lactonas/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Interações de Medicamentos , Doenças das Valvas Cardíacas/induzido quimicamente , Humanos , Síndromes de Malabsorção/induzido quimicamente , Neoplasias/induzido quimicamente , Orlistate , Síndrome da Serotonina/induzido quimicamente , Estados Unidos , United States Food and Drug Administration
13.
Expert Opin Drug Saf ; 14(2): 185-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25529104

RESUMO

Obesity is a common and morbid disease, but its treatment remains far from ideal. Many doctors, regulatory agencies, media outlets and patients consider lifestyle modification as the only possible intervention. Pharmacological agents, although with limitations, are useful weapons but are highly stigmatized. Some reasons for this stigma are discussed in this editorial and include: the failure of short-term medication use to achieve long-term results (due to the chronic and recurrent condition of obesity); common perception of obesity as a lifestyle choice; difficulty to treat obesity in the primary care setting; less than desired weight-loss results with medications; misuse of medications for cosmetic reasons; and unfavorable history of other anti-obesity drugs that were withdrawn in previous decades.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológico , Estereotipagem , Fármacos Antiobesidade/efeitos adversos , Humanos
14.
Arq. bras. endocrinol. metab ; 58(9): 889-899, 12/2014. tab
Artigo em Inglês | LILACS | ID: lil-732180

RESUMO

Brown adipose tissue, an essential organ for thermoregulation in small and hibernating mammals due to its mitochondrial uncoupling capacity, was until recently considered to be present in humans only in newborns. The identification of brown adipose tissue in adult humans since the development and use of positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG) has raised a series of doubts and questions about its real importance in our metabolism. In this review, we will discuss what we have learnt since its identification in humans as well as both new and old concepts, some of which have been marginalized for decades, such as diet-induced thermogenesis. Arq Bras Endocrinol Metab. 2014;58(9):889-99.


O tecido adiposo marrom, órgão essencial para a termorregulação de animais hibernantes e pequenos devido à sua capacidade desacopladora, era até poucos anos considerado presente apenas em recém-nascidos na espécie humana. A identificação do tecido adiposo marrom em adultos com o desenvolvimento e uso da tomografia de emissão de pósitron marcado com 18-fluorodesoxiglicose (PET-FDG) gerou questões sobre sua real importância para nosso metabolismo. Nesta revisão, discutiremos o que aprendemos nesse tempo, assim como conceitos antigos e novos, alguns marginalizados por décadas, como a termogênese induzida por dieta. Arq Bras Endocrinol Metab. 2014;58(9):889-99.


Assuntos
Adulto , Humanos , Tecido Adiposo Marrom/fisiologia , Canais Iônicos/metabolismo , Proteínas Mitocondriais/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Metabolismo Energético/fisiologia , /farmacocinética , Obesidade/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Termogênese/fisiologia
15.
Arq Bras Endocrinol Metabol ; 58(9): 889-99, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25627043

RESUMO

Brown adipose tissue, an essential organ for thermoregulation in small and hibernating mammals due to its mitochondrial uncoupling capacity, was until recently considered to be present in humans only in newborns. The identification of brown adipose tissue in adult humans since the development and use of positron emission tomography marked with 18-fluorodeoxyglucose (PET-FDG) has raised a series of doubts and questions about its real importance in our metabolism. In this review, we will discuss what we have learnt since its identification in humans as well as both new and old concepts, some of which have been marginalized for decades, such as diet-induced thermogenesis.


Assuntos
Tecido Adiposo Marrom/fisiologia , Canais Iônicos/metabolismo , Proteínas Mitocondriais/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Adulto , Metabolismo Energético/fisiologia , Fluordesoxiglucose F18/farmacocinética , Humanos , Obesidade/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Termogênese/fisiologia , Proteína Desacopladora 1
16.
Expert Rev Clin Pharmacol ; 6(3): 235-41, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23656337

RESUMO

The aim of this article is to focus on the fixed-dose combination of phentermine and topiramate, a new antiobesity drug recently approved by the US FDA. The mechanisms of weight loss for each drug in monotherapy is described, followed by the rationale for its use as a combination therapy and a comprehensive review of recently published clinical trials that assessed its efficacy  and safety.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Depressores do Apetite/uso terapêutico , Frutose/análogos & derivados , Obesidade/tratamento farmacológico , Fentermina/uso terapêutico , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Frutose/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Topiramato , Resultado do Tratamento
17.
Pharmaceuticals (Basel) ; 3(8): 2398-2415, 2010 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-27713360

RESUMO

Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine) approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry.

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