Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso).

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusion: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Brazilian evidence-based guideline for screening, diagnosis, treatment, and follow-up of metabolic dysfunction-associated steatotic liver disease (MASLD) in adult individuals with overweight or obesity: A joint position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM), Brazilian Society of Hepatology (SBH), and Brazilian Association for the Study of Obesity and Metabolic Syndrome (Abeso)

ABSTRACT Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD. Material and methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria. Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up, 14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment. Conclusions: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Impact of 6 months of treatment with intragastric balloon on body fat and quality of life in obese individuals with metabolic syndrome.

BACKGROUND: Obesity is a worldwide public health issue with a negative impact on quality of life. Different weight loss interventions have demonstrated improvements in quality of life. The aim of this study was to investigate the effect of 6 months of treatment with an intragastric balloon (IGB) on health-related quality of life (HRQOL) and its relation to changes in body fat in obese individuals with metabolic syndrome (MS). METHODS: Fifty obese patients with MS aged 18-50 were selected for treatment with IGB for 6 months. Body fat was assessed with anthropometric measures and dual-energy X-ray absorptiometry (DXA) at baseline and after removal of the IGB. HRQOL was evaluated with the short form of the World Health Organization Quality of Life (WHOQOL-BREF) at baseline and soon after removal of the IGB. RESULTS: Thirty-nine patients completed the study. After 6 months, there was a significant improvement in quality of life (p = 0.0009) and health (p < 0.0001) perceptions, and in the Physical (p = 0.001), Psychological (p = 0.031), and Environmental domains (p = 0.0071). Anthropometric measures and total fat determined by DXA were directly and significantly related to an improvement in general aspects of quality of life. The decrease in the percentage of total fat was the parameter that better correlated with improvements in quality of life perception after regression (p = 0.032). CONCLUSIONS: In obese individuals with MS, weight loss parameters were associated with short-term improvements in HRQOL after 6 months of treatment with IGB. However, only total fat was independently related to HRQOL perception. TRIAL REGISTRATION: ClinicalTrials.gov NCT01598233 .

Serum TSH levels are associated with cardiovascular risk factors in overweight and obese adolescents / Níveis de TSH sérica associados a fatores de risco cardiovascular em adolescentes acima do peso e obesos

Abstract Objective: To investigate the relationship between serum thyrotropin (TSH), insulin resistance (IR), and cardiovascular risk factors (CRF) in a sample of overweight and obese Brazilian adolescents. Methods: A retrospective, longitudinal analysis of 199 overweight and obese pubescent adolescents was performed. The TSH and free T4 (fT4) levels, anthropometric measurements, and laboratory test results of these patients were analyzed. Results: 27 individuals (13.56%) presented with TSH levels above the normal level (subclinical hypothyroidism [SCH]). Their waist circumference (WC) was significantly higher than those of euthyroid individuals. Serum TSH was positively correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) index, triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Using TSH and BMI as independent variables, TSH levels were shown to be independently related to HOMA-IR (p = 0.001) and TG (p = 0.007). Among euthyroid subjects, individuals with TSH values <2.5 mIU/mL exhibited statistically significant decreases in waist-to-hip ratio, HDL-C levels, and HOMA-IR scores and a tendency toward lower WC values. Conclusion: SCH in overweight and obese adolescents appears to be associated with excess weight, especially visceral weight. In euthyroid adolescents, there appears to be a direct relationship between TSH and some CRF. In conclusion, in the present sample of overweight and obese adolescents, TSH levels appear to be associated with IR and CRF.

Resumo Objetivo Investigar a relação entre tireotrofina sérica (TSH), resistência à insulina (RI) e fatores de risco cardiovascular (FRC) em uma amostra de adolescentes brasileiros acima do peso e obesos. Métodos Foi realizada uma análise longitudinal retrospectiva de 190 adolescentes púberes acima do peso e obesos. Foram analisados os níveis de TSH e T4 livre (T4l), as medidas antropométricas e os resultados de exames laboratoriais desses pacientes. Resultados 27 indivíduos (13,56%) apresentaram níveis de TSH acima do normal (hipotireoidismo subclínico (HSC)). Eles apresentaram circunferência da cintura (CC) significativamente maior que os indivíduos eutireoideos. A TSH sérica foi positivamente correlacionada ao índice do modelo de avaliação da homeostase de resistência à insulina (HOMA-IR), triglicerídeos (TG) e lipoproteína de alta densidade-colesterol (HDL-C). Usando TSH e IMC como variáveis independentes, os níveis de TSH estavam relacionados ao HOMA-IR (p = 0.001) e a TG (p = 0.007) de forma independente. Entre os pacientes eutireoideos, indivíduos com valores de TSH < 2.5 mIU/mL apresentaram reduções estatisticamente significativas na razão cintura/quadril, nos níveis de HDL-C e nos escores de HOMA-IR e tendência a menores valores de CC. Conclusão O HSC em adolescentes acima do peso e obesos parece estar associado ao excesso de peso, principalmente de peso visceral. Em adolescentes eutireoideos, parece haver uma relação direta entre TSH e alguns FRC. Concluindo, em nossa amostra de adolescentes acima do peso e obesos, os níveis de TSH parecem estar associados a RI e FRC.

Serum TSH levels are associated with cardiovascular risk factors in overweight and obese adolescents.

OBJECTIVE: To investigate the relationship between serum thyrotropin (TSH), insulin resistance (IR), and cardiovascular risk factors (CRF) in a sample of overweight and obese Brazilian adolescents. METHODS: A retrospective, longitudinal analysis of 199 overweight and obese pubescent adolescents was performed. The TSH and free T4 (fT4) levels, anthropometric measurements, and laboratory test results of these patients were analyzed. RESULTS: 27 individuals (13.56%) presented with TSH levels above the normal level (subclinical hypothyroidism [SCH]). Their waist circumference (WC) was significantly higher than those of euthyroid individuals. Serum TSH was positively correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) index, triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C). Using TSH and BMI as independent variables, TSH levels were shown to be independently related to HOMA-IR (p=0.001) and TG (p=0.007). Among euthyroid subjects, individuals with TSH values <2.5mIU/mL exhibited statistically significant decreases in waist-to-hip ratio, HDL-C levels, and HOMA-IR scores and a tendency toward lower WC values. CONCLUSION: SCH in overweight and obese adolescents appears to be associated with excess weight, especially visceral weight. In euthyroid adolescents, there appears to be a direct relationship between TSH and some CRF. In conclusion, in the present sample of overweight and obese adolescents, TSH levels appear to be associated with IR and CRF.

Dipeptidyl Peptidase 4: A New Link between Diabetes Mellitus and Atherosclerosis?

Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is undoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides secreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the pathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of T2DM. DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems to be increased and there are a growing number of in vitro and in vivo studies suggesting that this enzyme could be a new link between T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is expected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the prevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that reinforce the associations between DPP4, atherosclerosis, and T2DM.

Evaluation of epicardial adipose tissue in familial partial lipodystrophy.

BACKGROUND: Dunnigan type Familial Partial Lipodystrophy (FPLD) is characterized by loss of subcutaneous fat from the limbs and excessive accumulation on the visceral adipose tissue (VAT). Affected individuals have insulin resistance (IR), diabetes, dyslipidemia and early cardiovascular (CV) events, due to their imbalanced distribution of total body fat (TBF). Epicardial adipose tissue (EAT) is correlated with VAT. Hence, EAT could be a new index of cardiac and visceral adiposity with great potential as a marker of CV risk in FPLD. OBJECTIVE: Compare EAT in FPLD patients versus healthy controls. Moreover, we aimed to verify if EFT is related to anthropometrical (ATPM) and Dual-Energy X-ray Absorptiometry (DEXA) measures, as well as laboratory blood findings. We postulated that FPLD patients have enlarged EAT. METHODS: This is an observational, cross-sectional study. Six patients with a confirmed mutation in the LMNA gene for FPLD were enrolled in the study. Six sex, age and BMI-matched healthy controls were also selected. EFT was measured by transthoracic echocardiography (ECHO). All participants had body fat distribution evaluated by ATPM and by DEXA measures. Fasting blood samples were obtained for biochemical profiles and also for leptin measurements. RESULTS: Median EFT was significantly higher in the FPLD group than in matched controls (6.0 ± 3.6 mm vs. 0.0 ± 2.04 mm; p = 0.0306). Additionally, FPLD patients had lower leptin values. There was no significant correlation between EAT and ATPM and DEXA measurements, nor laboratory findings. CONCLUSIONS: This study demonstrates, for the first time, that EAT measured by ECHO is increased in FPLD patients, compared to healthy controls. However, it failed to prove a significant relation neither between EAT and DEXA, ATPM or laboratory variables analyzed.

A rare case of Cushing syndrome by cyclic ectopic-ACTH.

ACTH-dependent Cushing syndrome (CS) due to ectopic ACTH production is most times difficult to manage. The identification of the source of ACTH may take many years. Surgery or chemotherapy for the primary tumor is not always possible. Control of Cushing symptoms is many times achieved using medication, or bilateral adrenalectomy in refractory cases. This case presents a Brazilian male who showed severe hypertension, mood changes, muscle weakness, darkening of skin, and increased abdominal fat. An investigation for Cushing syndrome was carried out and, after a four-year follow-up, a carotid glomus tumor (chemodectoma) was confirmed, a rare ectopic ACTH-producing tumor. Besides, the patient presented cyclic Cushing syndrome that was exacerbated by diverticulitis episodes. This case presents interesting pitfalls on diagnosis and management of ACTH-dependent CS. This is the only report of a chemodectoma that produced ACTH in the literature.

A rare case of Cushing syndrome by cyclic ectopic-ACTH / Um caso raro de síndrome de Cushing associada a ACTH-ectópico cíclico

ACTH-dependent Cushing syndrome (CS) due to ectopic ACTH production is most times difficult to manage. The identification of the source of ACTH may take many years. Surgery or chemotherapy for the primary tumor is not always possible. Control of Cushing symptoms is many times achieved using medication, or bilateral adrenalectomy in refractory cases. This case presents a Brazilian male who showed severe hypertension, mood changes, muscle weakness, darkening of skin, and increased abdominal fat. An investigation for Cushing syndrome was carried out and, after a four-year follow-up, a carotid glomus tumor (chemodectoma) was confirmed, a rare ectopic ACTH-producing tumor. Besides, the patient presented cyclic Cushing syndrome that was exacerbated by diverticulitis episodes. This case presents interesting pitfalls on diagnosis and management of ACTH-dependent CS. This is the only report of a chemodectoma that produced ACTH in the literature.

A síndrome de Cushing ACTH-dependente causada por produção ectópica de ACTH é, muitas vezes, difícil de diagnosticar e conduzir. A identificação da fonte produtora de ACTH pode demorar muitos anos. A cirurgia ou quimioterapia para o tumor primário nem sempre é possível, sendo o controle do hipercortisolismo alcançado com uso de fármacos ou adrenalectomia bilateral, nos casos refratários. Este caso apresenta um homem com hipertensão grave, mudança de humor, fraqueza proximal, escurecimento da pele e aumento de gordura abdominal. A investigação para síndrome de Cushing foi feita e, após quatro anos de acompanhamento, confirmou-se um tumor de glomus carotídeo (quemodectoma), causa rara de tumor secretor de ACTH. Nesse período, o paciente apresentou síndrome de Cushing cíclica, exacerbada por crises de diverticulite. O caso ilustra pontos importantes no diagnóstico, no acompanhamento e na condução da síndrome de Cushing ACTH-dependente, sendo este o único caso de tumor de glomus de carótida produzindo ACTH descrito na literatura médica.

Relação entre a síndrome metabólica, teor de gordura intramiocelular e os níveis plasmáticos da adiponectina: papel da rosiglitazona / Relationship between metabolic syndrome intramyocellular lipid content and plasma levels of adiponectin: role of rosiglitazone

Objetivos - A resistência à insulina está associada com o aumento do teor de gordura intramiocelular (GIMC) e com níveis séricos da adiponectina (ADP) diminuídos. A ADP por sua vez está envolvida na oxidação de gordura muscular. Entretanto, a relação entre ambas continua controversa. O objetivo deste estudo é explorar a relação entre a ADP e a GIMC em adultos não diabéticos, além de estudar o papel da rosiglitasona (RSG) sobre a distribuição da gordura entre os compartimentos musculares. Desenho do estudo - Este estudo compreende duas fases: uma fase transversal (corte-transversal) e uma fase longitudinal, de intervenção terapêutica com uma droga, num desenho aberto. Local - Laboratório de Pesquisas Clínicas e Experimentais em Biologia Vascular (Biovasc) - UERJ. Material e métodos - Na fase transversal, 24 pacientes obesos, não diabéticos, com síndrome metabólica (SM) e 9 controles magros e saudáveis foram estudados. Foi realizada a Espectroscopia de Prótons por Ressonância Nuclear Magnética (1H-ERNM) para quantificar a gordura extramiocelular (GEMC) e a GIMC. Estas, associadas à ADP e aos parâmetros antropométricos e bioquímicos, foram avaliadas e comparadas nos dois grupos. Durante a fase longitudinal, 15 destes pacientes foram reestudados, através da 1H-ERNM, após o tratamento com RSG por 6 meses. Da mesma forma, as variáveis antropométricas e metabólicas foram reavaliadas. Resultados - Fase transversal: os pacientes com SM apresentaram maior índice de massa corporal (IMC), cintura abdominal, relação cintura-quadril (RCQ), e níveis de glicemia, insulina e triglicerídeos e menores níveis de HDL-c, quando comparados com o grupo controle. Da mesma forma o HOMA-RI [3.25 (2.58-4.13) vs 1.02 (0.73-1.29); p<0.0001] e a GIMC [266.1 (189.9-296.3) vs 72.85 (55.3-109.4) unidades arbitrárias-UA, p<0.0001] estavam aumentados enquanto o QUICKI [0.32 (0.31-0.33) vs 0.38 (0.37-0.40); p<0.0001] e a ADP [8.6 (4.05-15.95) vs 21.1 (12.9-24.4) ug/ml; p=0.02) estavam diminuídos...

Study objective - insulin resistance (IR) is associated with intramyocellular lipid (IMCL) content and low serum adiponectin (ADP) levels. ADP is also involved in muscle fat oxidation but the relationship between them is still controversial. We aimed to further explore the relationship between ADP and IMCL content in non-diabetic adults and the role of rosiglitazone (RSG) in muscle fat compartment distribution in an adult population of obese non-diabetic metabolic syndrome patients. Design - this study comprises two phases: a cross-sectional and a longitudinal, open-label, drug-interventional one. Setting - Laboratory for Clinical and Experimental Research on Vascular Biology (Biovasc) at the State University of Rio de Janeiro. Material and Methods - during the cross-sectional phase, 24 obese, non-diabetic patients with metabolic syndrome (MS) and 9 lean healthy controls were studied. Proton nuclear magnetic resonance spectroscopy (1H-NMRS) was performed to quantify IMCL, as well as extramyocellular lipid (EMCL) content. The latter plus serum ADP, anthropometrics and biochemical parameters were evaluated and compared in these two groups. During the longitudinal phase, fifteen of the MS patients were studied by means of 1H-NMRS before and after treatment with 8mg/day of RSG for 6 months. Anthropometrical and metabolic variables were assessed. Measurements and main results - cross-sectional phase: MS patients had higher body mass index (BMI), waist, waist-to-hip ratio (WHR), glucose, insulin and triglycerides and lower HDL-c as compared to controls. HOMA-IR (3.25 [2.58-4.13] vs 1.02 [0.73-1.29]; p<0.0001) and IMCL content (266.1 [189.9-296.3] vs 72.85 [55.3-109.4) AU, p<0.0001] were higher, and QUICKI (0.32 [0.31-0.33] vs 0.38 [0.37-0.40]; p<0.0001) and ADP (8.6 [4.05-15.95] vs 21.1 [12.9-24.4] ug/ml; p=0.02) lower in MS compared to controls. IMCL content was directly associated with glucose, insulin, triglycerides and HOMA-IR and inversely to HDLc, QUICKI...