Osvaldo Kohlmann Junior

Obesidade visceral, hipertensão arterial e risco cárdio-renal: uma revisão

Great part of obesity adversity is due to its cardiovascular/coronary risk, particularly present in obese with visceral adiposity distribution. Visceral fat deposition is known to be associated with a greater prevalence of metabolic, neurohormonal, inflammatory and hemodynamic disorders, which together will be implicated in microvascular and target organ involvement, particularly to the cardio-renal axis. In this aspect, beyond its classical association with coronary disease, visceral obesity has been associated with left ventricular hypertrophy and microalbuminuria, which are known cardiac and nephrologic risk factors. So, therapeutic tools for obese patients, specially for those with hypertension, must accomplish the risk stratification based on body fat distribution, which will allow a more adequate therapy in terms of risk factors control as well as target organ damage monitoring.

Modelos experimentais de resistência à insulina e obesidade: lições aprendidas

For better understanding the role of each element involved in the physiopathology of obesity and insulin resistance, researchers can use experimental models, which may in controlled manner evaluate the participation of each element on the obesity and insulin resistance and provide information for better understanding the physiopathology and treatment of obesity and insulin resistance. Experimental obesity and insulin resistance can be due to a deficient response to leptin, secondary to hypoleptinemia and/or mutations on leptin receptor, by modifications on insulin receptor, deletion or diminished insulin signal transduction, enhancement of the effects of orexigen peptides and/or diminution of anorexigen peptides actions on hypothalamus, as well as secondary to arterial hypertension, as in the spontaneously hypertension. Obesity and insulin resistance can also be induced by glucocorticoid excess, frutose enriched and cafeteria diet and due to hypothalamus lesions induced by neonatal administration of monossodium glutamate.

Efeitos de diferentes graus de sensibilidade a insulina na função endotelial de pacientes obesos

BACKGROUND Obesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals. OBJECTIVE To assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components. METHODS Forty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13). RESULTS We found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2 ± 7.0 vs 18.0 ± 7.5 %, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides. CONCLUSION Our data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.FUNDAMENTO: A obesidade derivada da deposicao de gordura intra-abdominal tende a aumentar a producao de hormonios e citoquinas, piorando a sensibilidade a insulina e levando a disfuncao endotelial. A hiperinsulinemia e considerada um fator de risco independente para doenca isquemica cardiaca e e uma causa de disfuncao endotelial em individuos saudaveis. OBJETIVO: Avaliar o impacto de diferentes graus de resistencia a insulina, medida pelo HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), sobre a funcao endotelial de obesos, pacientes nao diabeticos, sem historia previa de eventos cardiovasculares e diversos componentes da sindrome metabolica. METODOS: Um total de 40 individuos obesos foi submetido a medidas antropometricas, pressao arterial de consultorio, MAPA e exames laboratoriais, alem de avaliacao ultrassonografica nao invasiva da funcao endotelial. Os pacientes foram divididos em tres grupos de acordo com o grau de resistencia a insulina: pacientes com valores de HOMA-IR entre 0,590 e 1,082 foram incluidos no Grupo 1 (n = 13); entre 1,083 e 1,410 no Grupo 2 (n = 14); e entre 1,610 e 2,510 no Grupo 3 (n = 13). RESULTADOS: Encontramos uma diferenca significativa na vasodilatacao mediada por fluxo no Grupo 3 em relacao ao Grupo 1 (9,2 ± 7,0 vs 18,0 ± 7,5 %, p = 0,006). Houve uma correlacao negativa entre a funcao endotelial e insulina, HOMA-IR e triglicerides. CONCLUSAO: Nosso estudo sugere que leves alteracoes nos niveis de resistencia a insulina avaliada pelo HOMA-IR podem causar algum impacto sobre a funcao vasodilatadora do endotelio em individuos obesos nao complicados com diferentes fatores de risco cardiovascular.

Efeito da sobreposição de um modelo de obesidade neuroendócrina experimental e hipertensão arterial sobre a pressão arterial, peso corporal e parâmetros metabólicos e renais de ratos

r esuMo Introducao: A elevacao do indice de massa corporal e a presenca de sindrome metabolica se associam com diminuicao da funcao renal e o aparecimento de doenca renal terminal. Objetivo: Avaliar o efeito da sobreposicao de um modelo de obesidade experimental e hipertensao arterial sobre a pressao arterial, peso corporal e parâmetros metabolicos e renais de ratos. Metodos: Foram estudados ratos machos das cepas Wistar e espontaneamente hipertensos (SHR). Os grupos MSG receberam glutamato monossodico no periodo neonatal (WST + MSG e SHR + MSG). Os animais controles receberam

Efeito do exercício físico e suplementação de potássio sobre a pressão arterial, metabolismo glicídico e albuminúria de ratos hipertensos

INTRODUCTION It is still controversial whether there are synergistic effects among different non-pharmacological interventions used in the treatment of hypertension. OBJECTIVES To evaluate the effect of aerobic exercise, oral supplementation of potassium and their combination on blood pressure, glucose metabolism, urinary albumin excretion and glomerular morphology in spontaneously hypertensive rats (SHR). METHODS SHR were divided into groups: Control Group (SHR; standard diet and sedentary, n = 10), Exercise Group (SHR + E; trained on a treadmill, standard diet, n = 10), Potassium Group (SHR + K; sedentary, potassium supplementation, n = 10) and Group Exercise + Potassium (SHR + E + K, exercise, potassium supplementation n = 10). Weekly, body weight (BW) and tail blood pressure (TAP) were measured. At the end of 16 weeks, a Oral Glucose Tolerance Test was performed. Albuminuria was determined in the baseline period, at 8th and at 16th week. After sacrifice, the analysis of glomerular sclerosis index and visceral fat weight was performed. RESULTS The TAP and BW did not change significantly. There was improvement in insulin sensitivity in SHR + E and SHR + K, but not in SHR + E + K. At week 16, albuminuria in all groups was significantly lower than the SHR control. The glomerular sclerosis index and visceral fat content were also significantly lower in all groups compared to control. CONCLUSION An oral supplementation of potassium and exercise led to an improvement in glucose metabolism, in albuminuria and glomerular morphology, however, the overlap of the treatments did not show synergism.

Manidipina no tratamento da hipertensão arterial essencial estágio I e II do paciente com sobrepeso ou obesidade andróide. Estudo multicêntrico brasileiro de eficácia, tolerabilidade e efeitos metabólicos

OBJECTIVE: To evaluate the efficacy, metabolic effects and tolerability of manidipine used in the treatment of stage I and II essential hypertensive patients with overweight or android obesity. METHODS: By an open-label, non comparative protocol in 11 Brazilian clinical research centers 102 hypertensive patients of both sexes with over weight or central obesity were treated with manidipine 10 to 20mg once daily for 12 weeks. Blood pressure, heart rate and adverse events were monitored. Fasting plasma glucose, total, HDL and LDL-cholesterol and triglicerides were determined at both placebo period and end of active treatment. Also in 12 patients, insulin sensitivity index was evaluated during placebo and manidipine treatment. RESULTS: Blood pressure was reduced from 159±15 / 102±5mmHg to 141±15 / 90±8mmHg with the treatment without any noticeable change in heart rate. Manidipine-efficacy rate was 71.9% with 51.1% of blood pressure normalization. No significant changes in metabolic parameters were noticed. Tolerability to manidipine was very high and at the last visit 87.1% of the treated patients were free of any adverse event. CONCLUSION: Manidipine is an adequate, highly effective, exempt of metabolic effects and safe option for treatment of stage I and II essential hypertensive patients with overweight or android obesity.

Efeito da associação entre obesidade neuroendócrina e exócrina experimental sobre a pressão arterial de cauda e o metabolismo de glicose de ratos Wistar

OBJECTIVE: To study two different models of obesity, exocrine and endocrine, and its association on tail arterial pressure (TAP), body weight (BW), glucose metabolism and visceral fat content. METHODS: Male Wistar rats were studied. The MSG group was composed by rats that received of MSG in neonatal period. At the 3rd month of life, part of these animals received cafeteria diet. Animals received saline control in the neonatal period. In the 12 weeks of study, body weight and blood pressure were measured twice a week. In the end of this period on, Oral Glucose Tolerance Test (OGTT) was performed and the Insulin Sensitivity Index (ISI) was calculated, also the left Relative Ventricular Weight (RLW) and Relative Epididimal Fat Weight (REFW) were obtained. RESULTS: No changes on BW and TAP were verified. The obesity induced by MSG and CAF, individually, let to increases on insulin resistance (WST = 23,25 ± 9,31; CAF = 15,92 ± 9,10*; MSG = 13,41 ± 3,84* mg-1mU-1, p < 0,05 vs WST) and relative epididimal fat content (WST = 6,20 ± 0,57; CAF = 8,27 ± 1,53*; MSG = 8,23 ± 1,98* g/100 g, *p < 0,05) when these rats were compared to control rats. An enhanced effect upon these parameters was observed with the association of both obesity models (MSG+CAF = 9,34 ± 5,77 mg-1mU-1, p < 0,05 vs MSG and CAF) and visceral fat content (MSG+CAF = 11,12 ± 3,85 g/100g, p < 0,05 vs MSG and CAF). CONCLUSION: The association of these two experimental models of obesity aggravates insulin resistance that probably is due at least in part to the increase of visceral fat content.