Previous hepatitis E virus infection, cirrhosis and insulin resistance in patients with chronic hepatitis C

ABSTRACT Background: Hepatitis E virus (HEV) infection in patients with pre-existing liver disease has shown high morbidity and lethality. The consequences of HEV superinfection in patients with chronic hepatitis C virus (HCV) infection are not fully understood. This study aimed to evaluate the association between the presence of anti-HEV antibodies, liver cirrhosis, and insulin resistance. Methods: A total of 618 patients chronically infected with HCV were included from three reference centers for viral hepatitis in São Paulo, Brazil. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). Results: The seroprevalence of anti-HEV in patients with cirrhosis was significantly higher than in patients without cirrhosis (13.2% vs 8%, OR = 1.74, p = 0.04). Seropositivity for anti-HEV, adjusted for sex, age, and HCV genotype showed an association trend with hepatic cirrhosis (aOR = 1.75, p = 0.059). Presence of HEV antibodies, adjusted for age, body mass index and cirrhosis, was shown to be independently associated with insulin resistance (aOR: 4.39; p = 0.045). Conclusion: Patients with chronic hepatitis C are under risk of hepatitis E virus superinfection in Brazil. The trend toward association between cirrhosis and previous HEV infection suggests that it may accelerate liver fibrosis in patients with chronic hepatitis C. In addition, previous infection by HEV is independently associated with insulin resistance in the studied population, which may be an extra-hepatic manifestation of hepatitis E that persists after resolution of the active infection, and may contribute to fibrosis progression.

Immunoinflammatory mediators in the pathogenesis of diabetes mellitus / Mediadores imunoinflamatórios na patogênese do diabetes mellitus

ABSTRACT Characterized as a metabolic syndrome with multiple consequences for the lives of patients, diabetes mellitus is also classified as a chronic non-communicable disease of great scope in the world. It is a complex disease, with different points of view, including the relation between inflammatory process, obesity and insulin resistance due to the performance of the various immunoinflammatory mediators - called adipokines - on glycemic homeostasis. Recent studies have precisely addressed this aspect for the development of drugs that assist in the protection of pancreatic ß cells from the damages arising from oxidative stress and inflammatory process, in order to control the hyperglycemic picture, which is characteristic of diabetes mellitus.

RESUMO Caracterizado como uma síndrome metabólica de múltiplas consequências para a vida de seus portadores, o diabetes mellitus é também classificado como uma doença crônica não transmissível de grande abrangência no mundo. Trata-se de uma doença complexa, com diversos pontos de vista, dentre eles a relação entre processo inflamatório, obesidade e resistência à ação da insulina, devido à atuação dos diversos mediadores imunoinflamatórios, chamados de adipocinas, sobre a homeostase glicêmica. Recentes estudos têm abordado justamente este aspecto para o desenvolvimento de fármacos que auxiliem na proteção das células ß pancreáticas dos danos advindos do estresse oxidativo e processo inflamatório, de modo a controlar o quadro hiperglicêmico característico do diabetes mellitus.

Obesity is the main determinant of insulin resistance more than the circulating pro-inflammatory cytokines levels in rheumatoid arthritis patients / A obesidade é um determinante da resistência à insulina mais importante do que os níveis circulantes de citocinas pró-inflamatórias em pacientes com artrite reumatoide

ABSTRACT Background: Systemic blockade of TNF-α in Rheumatoid arthritis with insulin resistance seems to produce more improvement in insulin sensitivity in normal weight patients with Rheumatoid arthritis than in obese patients with Rheumatoid arthritis, suggesting that systemic-inflammation and obesity are independent risk factors for insulin resistance in Rheumatoid arthritis patients. Objectives: To evaluate the insulin resistance in: normal weight patients with Rheumatoid arthritis, overweight patients with Rheumatoid arthritis, obese Rheumatoid arthritis patients, and matched control subjects with normal weight and obesity; and its association with major cytokines involved in the pathogenesis of the disease. Methods: Assessments included: body mass index, insulin resistance by Homeostasis Model Assessment, ELISA method, and enzymatic colorimetric assay. Results: Outstanding results from these studies include: (1) In Rheumatoid arthritis patients, insulin resistance was well correlated with body mass index, but not with levels of serum cytokines. In fact, levels of cytokines were similar in all Rheumatoid arthritis patients, regardless of being obese, overweight or normal weight (2) Insulin resistance was significantly higher in Rheumatoid arthritis with normal weight than in normal weight (3) No significant difference was observed between insulin resistances of Rheumatoid arthritis with obesity and obesity (4) As expected, levels of circulating cytokines were significantly higher in Rheumatoid arthritis patients than in obesity. Conclusions: Obesity appears to be a dominant condition above inflammation to produce IR in RA patients. The dissociation of the inflammation and obesity components to produce IR suggests the need of an independent therapeutic strategy in obese patients with RA.

RESUMO Introdução: O bloqueio sistêmico do Fator de Necrose Tumoral-α (TNF-α) nos indivíduos com artrite reumatoide (AR) com resistência à insulina (RI) parece produzir mais melhoria na sensibilidade à insulina em pacientes com AR com peso normal do que em pacientes obesos com AR. Isso sugere que a inflamação sistêmica e a obesidade são fatores de risco independentes para a RI em pacientes com AR. Objetivos: Avaliar a resistência à insulina em pacientes com peso normal com AR (AR-PN), pacientes com sobrepeso com AR (AR-SP), pacientes com AR obesos (AR-OB) e indivíduos controle com peso normal (PN) e obesidade (OB) pareados; e a associação com as principais citocinas envolvidas na patogênese da doença. Métodos: As avaliações incluíram: índice de massa corporal (IMC), resistência à insulina com o modelo de avaliação da homeostase (Homa-IR), método Elisa e ensaio colorimétrico enzimático. Resultados: Os resultados marcantes do presente estudo incluíram: (1) Em pacientes com AR, a RI estava bem correlacionada com o Índice de Massa Corporal (quanto maior o IMC, maior a RI), mas não com os níveis séricos de citocinas. Na verdade, os níveis de citocinas eram semelhantes em todos os pacientes com AR, independentemente de serem obesos, com sobrepeso ou peso normal. (2) A RI foi significativamente maior no grupo AR-PN do que no grupo PN. (3) Não houve diferença estatisticamente significativa entre a RI de pacientes AR-OB e OB. (4) Como esperado, os níveis circulantes de citocinas foram significativamente maiores em pacientes com AR do que em OB. Conclusões: A obesidade parece ser uma condição mais importante do que a inflamação em produzir RI em pacientes com AR. A dissociação dos componentes da inflamação e da obesidade na produção de RI sugere a necessidade de uma estratégia terapêutica independente em pacientes obesos com AR.

Asociación entre niveles de testosterona, sensibilidad a la insulina, adiposidad y parámetros lipídicos en hombres / Association between testosterone levels, insulin sensitivity, adiposity and lipid parameters in men

Introducción: Evidencias sugieren que la testosterona interviene en la regulación del metabolismo de la glucosa y los lípidos.Objetivo: determinar la relación entre los niveles de testosterona y la sensibilidad a la insulina, la adiposidad y los parámetros del metabolismo lipídico en hombres.Métodos: estudio transversal y descriptivo en 225 hombres, entre 35 y 60 años, con y sin trastornos de la tolerancia a la glucosa. Se midieron: talla, peso, circunferencias de la cintura y de la cadera. Se realizaron determinaciones de insulina, glicemia, testosterona, colesterol, HDL-colesterol, LDL-colesterol y triglicéridos. Se determinaron índices de sensibilidad y resistencia a la insulina.Resultados: se encontró una correlación negativa entre los niveles de testosterona y la resistencia a la insulina, y los parámetros de adiposidad explorados (índice de masa corporal, circunferencias abdominal y de la cadera, índice cintura/cadera). El nivel de testosterona fue menor en los sujetos con hipertrigliceridemia. En los sujetos con trastornos de la tolerancia, se encontró un aumento significativo de la frecuencia de obesidad abdominal en presencia de valores bajos de testosterona.Conclusiones: existe una asociación directa entre los niveles de testosterona y la sensibilidad a la insulina en la población estudiada. La disminución de los niveles de testosterona en presencia de los desórdenes asociados al síndrome metabólico, sugiere la indicación de una evaluación metabólica temprana a los pacientes con hipogonadismo(AU)

Introduction: Evidence suggests that testosterone participates in the regulation of glucose and lipid metabolism.Objective: determine the relationship between testosterone levels and insulin sensitivity, adiposity and metabolism parameters in men.Methods: a descriptive cross-sectional study was conducted of 225 men aged 35-60 with and without glucose tolerance disorders. The variables measured were height, weight, and waist and hip circumference. Determinations were made for insulin, glycemia, testosterone, cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Insulin sensitivity and resistance were also determined.Results: a negative correlation was found between testosterone levels/insulin resistance and the adiposity parameters considered (body mass index, waist and hip circumference and waist to hip ratio). Testosterone levels were lower in subjects with hypertriglyceridemia. Patients with tolerance disorders showed a significant increase in the frequency of abdominal obesity in the presence of low testosterone values.Conclusions: a direct relationship was found between testosterone levels and insulin sensitivity in the population studied. Reduced testosterone levels in the presence of disorders associated to metabolic syndrome suggest the need for an early metabolic assessment of patients with hypogonadism(AU)

Estudo experimental da exposição ao PCB126 sobre a indução de Diabetes mellitus tipo II / Experimental study of PCB126 exposure on induction of Diabetes mellitus type II

A exposição ambiental aos poluentes orgânicos persistentes tem recebido amplo destaque na literatura recentemente devido à extensa associação entre o desenvolvimento de doenças metabólicas, obesidade e/ou diabetes mellitus, e a presença destes poluentes, principalmente os organoclorados, como as bifenilas policloradas (PCBs), no organismo. Por outro lado, os mecanismos de ação destes poluentes é controverso devido à elevada quantidade de representantes destas classes, gerando diversidade de protocolos de exposição e escassez de estudos experimentais. Por isto, foi objetivo deste trabalho elucidar os mecanismos de ação tóxica do PCB126, nas doses de 0,1; 1 ou 10 µg/kg de massa corpórea, em ratos Wistar machos, durante quinze dias, expostos por instilação intranasal. O procotolo de exposição empregado foi caracterizado e considerado suficiente para causar toxicidade, uma vez que foram observadas alterações no sistema imune, metabolismo e em parâmetros relacionados à gênese do diabetes mellitus. A caracterização da exposição foi determinada pela quantificação da concentração de PCB126 no fígado e pulmão (CG/MS) e pelo aumento da expressão do receptor aril hidrocarboneto (AhR) no rim, fígado, pulmão e tecido adiposo (Western Blot). O efeito imunossupressor do PCB126 foi evidenciado pelo comprometimento da produção de células na medula óssea e, consequentemente, no número de células totais no sangue circulante. Adicionalmente, foi evidenciada a interferência do poluente na via de ativação mediada por receptores acoplados à proteína G (GPCRs), principalmente em neutrófilos, alterando importantes funções destas células, como a expressão de moléculas de adesão, geração de espécies reativas de oxigênio e migração. Entre as alterações metabólicas observadas, destacamos o aumento dos níveis de triglicerídeos e colesterol sérico, aumento da liberação de ácidos graxos livres; aumento da atividade da enzima hepática gama glutamil transferase; aumento da resistência à insulina e aumento da geração de óxido nítrico pelas ilhotas de Langerhans, dados estes, possivelmente relacionados ao comprometimento das células beta (ß) pancreáticas, confirmados pelo aumento da expressão de GLUT4 no tecido adiposo, aumento da concentração de insulina sérica e aumento do estresse oxidativo nas ilhotas de Langerhans. Em conjunto, os dados obtidos destacam importantes alterações causadas pela exposição intranasal ao PCB126, evidenciando a participação do poluente na gênese do diabetes mellitus do tipo II

The environmental exposure to persistent organic pollutants has been widely highlighted in recent literature due to the extensive association between the development of metabolic diseases, obesity and/or diabetes mellitus, and presence of these pollutants, especially organochlorines such as polychlorinated biphenyls (PCBs) in organism. Moreover, the mechanisms of action of these pollutants are controversial due to the high number of PCBs congeners, diversity of exposure protocols and lack of experimental studies. Therefore, the aim of this study was to elucidate the mechanisms of PCB126's toxic action at doses of 0.1; 1 or 10 µg/kg body weight in male Wistar rats exposed by intranasal instillation for 15 days. The established exposure procotol was characterized and considered sufficient to cause toxicity since changes were observed in the immune system, metabolism and in parameters related to the pathogenesis of diabetes mellitus. Characterization of exposure was determined by quantifying the concentration of PCB126 in liver and lung (GC-MS) and by the increased expression of aryl hydrocarbon receptor (AhR) in kidney, liver, lung, and adipose tissue (Western blot). The immunosuppressive effect of PCB126 was evidenced by impairment of cell production in the bone marrow and thus the total number of cells in the circulation. In addition, the interference of the pollutant in the activation pathway mediated by G-protein coupled receptors (GPCRs), in particular in neutrophils, was observed by changing important functions of these cells such as the expression of adhesion molecules, reactive oxygen species generation, and migration. Among the metabolic changes observed, we highlight the increased levels of triglycerides and serum cholesterol, increased release of free fatty acids; increased gamma glutamyl transferase hepatic enzyme activity; increased insulin resistance and increased generation of nitric oxide by the islets of Langerhans, these data possibly related to the impairment of beta cells (ß) pancreatic function, suggested by the increased expression of GLUT4 in adipose tissue, increased serum insulin concentration and increased oxidative stress in the islets of Langerhans. Altogether, these results highlight important changes caused by intranasal exposure to PCB126, suggesting participation of the pollutant in the genesis of diabetes mellitus type II

The association of autoimmune thyroiditis and non-functional adrenal incidentalomas with insulin resistance

Objective Patients with incidental nonfunctioning adrenal adenoma are associated with increased risk of obesity, impaired glucose tolerance and dyslipidemia. We aimed to investigate the relationship between thyroid function, serum lipids and insulin resistance in patients with nonfunctioning adrenal incidentaloma. Subjects and methods Forty patients who had diagnosed as adrenal incidentaloma (AI) in our department were included in the study. Serum free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), anti-thyroperoxidase antibody (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab), lipid profile, hs-CRP, fasting insulin levels were measured and insulin resistance calculated by HOMA-IR. Thyroid volume (TV) was assessed. Results None of the patients showed specific signs and symptoms of hormone excess. TV, TSH and fT3 levels in the patient and control groups did not differ significantly (p > 0.05). The serum fT4, anti-TG Ab, anti-TPO Ab levels in the patient group were significantly higher than in the control group (p = 0.013, p < 0.0001, p = 0.016 respectively). The HOMA-IR, hs-CRP and HDL cholesterol levels in the AI patients were significantly higher than the control group (p = 0.034, p = 0.041, p = 0.002, respectively). Statistically significant relationship was found between HOMA-IR and thyroid volume (r = 0.373, p = 0.018), fT4 (r = 0.382, p = 0.015), hs-CRP (r = 0.512, p = 0.001), HDL cholesterol (r = 0,351 p = 0.026) in AI patients. There were significant correlation between anti-TG Ab, anti-TPO Ab and TSH levels in AI patients (r = 0.431 p = 0.006, r = 0.402 p = 0.012). Conclusions Patients with nonfunctioning adrenal incidentaloma have several metabolic disturbances. At the same time autoimmune thyroid disorders are more frequent in nonfunctioning adrenal incidentaloma patient so that thyroid functions must be evaluated in those patients. Arch Endocrinol Metab. 2015;59(1):42-6 .

Bloqueadores do sistema renina-angiotensina em ilhotas pancreáticas e fígado na obesidade induzida por dietas em camundongos / Renin-angiotensin system blockers in pancreatic islets and liver on diet-induced obesity in mice

As associações entre obesidade, doença hepática gordurosa não alcoólica (NAFLD) e diabetes mellitus tipo 2 (DM2) são bem estabelecidas, e o sistema renina-angiotensina (SRA) pode proporcionar uma ligação entre eles. O bloqueio do SRA em diferentes níveis pode estar relacionado a respostas na resistência à insulina, remodelagem do pâncreas e do fígado em um modelo de obesidade induzida por dieta. Camundongos C57BL/6 foram alimentados com uma dieta hiperlipídica (HF) durante oito semanas e depois tratados com alisquireno (50 mg/kg/dia), enalapril (30 mg/kg/dia) ou losartana (10 mg/kg/dia) por um período adicional de seis semanas. As drogas foram incorporadas na dieta. Avaliou-se a massa corporal (MC), pressão arterial, consumo e gasto energético (GE), metabolismo da glicose e lipídico, histopatologia pancreática e hepática, análise hormonal, imunohistoquímica, perfil gênico e/ou proteico do SRA no pâncreas, gliconeogênese hepática, sinalização da insulina, oxidação e acúmulo lipídico. Todos os inibidores do SRA reduziram significativamente o aumento da pressão arterial nos camundongos alimentados com dieta HF. O tratamento com enalapril, mas não alisquireno ou losartana, reduziu o ganho de MC e a ingestão alimentar; aumentou o GE; amenizou a intolerância à glicose e resistência à insulina; melhorou a massa de células alfa e beta; impediu a redução da adiponectina plasmática e restaurou a sensibilidade à leptina. Além disso, o tratamento com enalapril melhorou a expressão proteica nas ilhotas pancreáticas de Pdx1, GLUT2, ECA2 e do receptor Mas. O tratamento com losartana apresentou uma elevação na expressão proteica de AT2R no pâncreas...

The associations between obesity, NAFLD (non-alcoholic fatty liver disease) and diabetes are well established, and the renin–angiotensin system (RAS) may provide a link among them. . The blocking of the RAS at different levels may be related to responses on insulin resistance, remodeling of the pancreas and liver in a model of diet-induced obesity. Mice (C57BL/6) were fed on a high-fat (HF) diet for 8 weeks and then treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for an additional 6 weeks. The drugs were incorporated into the diet. We assessed body mass (BM), blood pressure, energy intake and expenditure (EE), glucose and lipid metabolism, pancreatic and hepatic histopathology, hormonal analysis, immunohistochemistry, the expression profile of genes and/or proteins affecting pancreas RAS, hepatic gluconeogenesis, insulin signaling and lipid oxidation and accumulation. All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated BM gain, increased EE, enhanced the glucose intolerance and insulin resistance; improved the alpha and beta cell mass; prevented the reduction of plasma adiponectin and restored leptin sensibility. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression in the pancreas. In the liver, the enalapril administration improved hepatic steatosis, triglycerides and prevented the increase hepatic protein levels of PEPCK, G6Pase and GLUT2...

Factores de riesgo para el desarrollo del síndrome de resistencia a la insulina en el trasplante renal / Risk factors for development of insulin-resistance syndrome in the renal transplant

Introducción: el síndrome de resistencia a la insulina es una complicación frecuente en el trasplante renal, derivado de múltiples factores. Objetivo: conocer cuáles alteraciones vinculadas al trasplante renal y su tratamiento constituyen factores de riesgo para la aparición del síndrome de resistencia a la insulina. Métodos: se realizó un estudio de casos y controles en 81 pacientes con trasplante renal, supervivencia del injerto mayor de 1 año y que no fueran diabéticos antes del implante. Se conformaron 2 grupos, uno de enfermos con el síndrome, n=39, según los criterios del ATPIII y otro control, n=42. Para detectar factores de riesgo se compararon: variables pretrasplante (edad del receptor, tiempo en diálisis, cifras de glucemia, colesterol y triglicéridos, índice de masa corporal, infección por el virus de la hepatitis C, antecedentes familiares de diabetes) y variables postrasplante (tratamiento inmunosupresor, dosis de esteroides al tercer mes del trasplante, niveles de ciclosporina A y presencia o no de rechazo). Las variables pretrasplante fueron categorizadas de forma conveniente para análisis univariado y multivariado en el que resultaron estadísticamente significativas, en el estudio univariado: el mayor tiempo en diálisis, la mayor edad del receptor, las cifras elevadas de glucemia pretrasplante, la positividad al virus C, el índice de masa corporal superior a 25 y los antecedentes familiares de diabetes, este último factor fue el único con representatividad estadística en el análisis multivariado. Al analizar las variables vinculadas al tratamiento inmunosupresor solo hallamos que los pacientes con el síndrome tenían valores medios de ciclosporinemia mayores, estadísticamente, que aquellos que no desarrollaron la complicación...

Introduction: the insulin-resistance syndrome (IRS) is a frequent complication in the renal transplantation due to multiple factors. Objective: to know which alterations linked to renal transplantation and its treatment are risk factors for appearance of insulin-resistance syndrome. Methods: a case-control study was conducted in 81 patients underwent renal transplantation, with a graft survival higher than 1 year and not to be diabetics before implant. Two groups were established, one including patients with this syndrome (n=39) according to the ATP-III criteria and another as control (n=42). To detect the risk factors pre-transplantation the following variables were compared: age or receptor, time in dialysis, glycemia figures, cholesterol and triglycerides, body mass index (BMI), infection for hepatitis C and a family history of diabetes and post-transplantation variables included immunosuppressive treatment, dose of steroids at third month post-transplantation, cyclosporine A levels and presence or not of rejection. The pre-transplantation variables were categorized in a suitable way for univariate and multivariate analysis where they were statistically significant, in the univariate study: the largest time in dialysis, the great age of recipient, the high figures of pre-transplantation glycemia, the positive to Virus C, body mass index higher than 25 and family history of diabetes, this latter factor was the only with statistic representativeness in multivariate analysis. Analyzing the variables linked to immunosuppressive treatment, only we note that patients with this syndrome had statistically mean values of cyclosporine higher than those without this complication...

Immunological and biochemical parameters of patients with metabolic syndrome and the participation of oxidative and nitroactive stress

Metabolic syndrome (MS) is a multifactorial disease involving inflammatory activity and endothelial dysfunction. The aim of the present study was to evaluate the relationship between the changes in lipoperoxidation, in immunological and biochemical parameters and nitric oxide metabolite (NOx) levels in MS patients. Fifty patients with MS (4 males/46 females) and 50 controls (3 males/47 females) were studied. Compared to control (Mann-Whitney test), MS patients presented higher serum levels (P < 0.05) of fibrinogen: 314 (185-489) vs 262 (188-314) mg/dL, C-reactive protein (CRP): 7.80 (1.10-46.50) vs 0.70 (0.16-5.20) mg/dL, interleukin-6: 3.96 (3.04-28.18) vs 3.33 (2.55-9.63) pg/mL, uric acid: 5.45 (3.15-9.65) vs 3.81 (2.70-5.90) mg/dL, and hydroperoxides: 20,689 (19,076-67,182) vs 18,636 (15,926-19,731) cpm. In contrast, they presented lower (P < 0.05) adiponectin: 7.11 (3.19-18.22) vs 12.31 (9.11-27.27) µg/mL, and NOx levels: 5.69 (2.36-8.18) vs 6.72 (5.14-12.43) µM. NOx was inversely associated (Spearman’s rank correlation) with body mass index (r = -0.2858, P = 0.0191), insulin resistance determined by the homeostasis model assessment (r = -0.2530, P = 0.0315), CRP (r = -0.2843, P = 0.0171) and fibrinogen (r = -0.2464, P = 0.0413), and positively correlated with hydroperoxides (r = 0.2506, P = 0.0408). In conclusion, NOx levels are associated with obesity, insulin resistance, oxidative stress, and inflammatory markers. The high uric acid levels together with reactive oxygen species generation may be responsible for the reduced NO levels, which in turn lead to endothelial dysfunction. The elevated plasma chemiluminescence reflecting both increased plasma oxidation and reduced antioxidant capacity may play a role in the MS mechanism.

Análise da relação de qualidade da dieta com nível de atividade física e destes com perfil lipídico e estado inflamatório em indivíduos de risco cardiometabólico / Analysis of the relationship between diet quality and physical activity level and these with lipid profile and inflammatory status in individuals at high cardiometabolic risk

Introdução: Baixo nível de atividade física (AF) associado ao alto consumo energético contribuíram para transição nutricional no Brasil. Estilo de vida saudável reverte em benefícios cardiometabólicos. Considerando que estado inflamatório subclínico media os danos ao sistema cardiovascular, é possível que hábitos de vida saudáveis melhorem os fatores de risco, via atenuação da inflamação. Instrumentos padronizados para medir qualidade da dieta e AF estão disponíveis, mas não estudos locais avaliando a relação destes fatores entre si com base nestes instrumentos, ou examinando suas associações com estado inflamatório e perfil lipídico. Objetivos: Este estudo avaliou a associação entre a versão brasileira do Healthy Eating Index (B-HEI) e nível de AF e destes com marcadores inflamatórios, índice de resistência à insulina e variáveis lipídicas em indivíduos com alto risco cardiometabólico. Métodos: Nesta análise transversal foram incluídos 204 participantes (64,7 por cento mulheres; média de idade de 54,1 anos) de Estudo de Prevenção de Diabetes do CSEscola da FSP-USP, com pré-diabetes ou de síndrome metabólica sem diabetes. Foram realizados questionários e coletas de sangue. Foram utilizados três recordatórios alimentares de 24h para obtenção do B-HEI. O nível de AF foi medido pela versão longa do IPAQ, sendo determinada a AF no lazer, na locomoção, AF total e tempo de TV. Coeficiente de Spearman foi empregado para testar correlações. Para avaliar a relação entre o B-HEI e AF e dos tercis destas variáveis com marcadores inflamatórios e HOMA-IR foi usada ANOVA. Para avaliar associações independentes do B-HEI, tendo como variáveis dependentes parâmetros lipídicos, inflamatórios ou HOMA-IR, usou-se regressão linear múltipla e, para associações independentes da AF como as mesmas variáveis, usou-se regressão logística, sendo obtidos odds ratios (OR) e p de tendência. Resultados: Nos tercis do B-HEI, o nível de AF não diferiu; à medida que melhorava a qualidade da dieta houve tendência à redução do tempo de TV (21,4±11,6; 20,5±11,5; 16,8±10,4 h/sem; p=0,09). Na regressão linear, a circunferência abdominal associou-se inversamente aos escores de B-HEI, mantendo-se marginalmente significante após ajuste para idade e sexo. No mesmo modelo, proteína C reativa associou-se negativamente ao índice (p=0.02). Concentrações de adiponectina apresentaram significância marginal na análise sem ajustes (p=0.06).

Relationship between HCV infection and Insulin resistance in non-obese non-diabetic patients

Hepatitis C is a major cause of liver-related morbidity and mortality and represents a major public health problem in Egypt and worldwide. There is growing evidence as regard to the association between hepatitis C virus [HCV] infection and type 2 diabetes mellitus. However, the mutual link and related virological implication have not been fully clarified. Insulin resistance [IR] plays a primary role in the development of type 2 DM. This is supported by the results of prospective longitudinal studies showing that IR is the best predictor of the development of type 2 DM, preceding its onset by 10-20 years. To assess the correlation between HCV morbidity and Insulin resistance [IR] detected by HOMA test in none diabetic none obese HCV patients. The study participants were subcategorized into two groups,Group [I]: included 867 healthy subjects [negative HCV RNA] as a control group. Group [II]: included 277 patients with chronic HCV as a study group. The 2 groups were subjected to thorough history taking, full clinical examination, Anthropometric study,ultrasonographic examination and laboratory investigations including liver functions, viral markers, and qualitative PCR for HCV RNA ,lipid profile, glucose profile and HOMA test. This study revealed higher insulin resistance in the HCV study group than the control group

Detection of visceral adiposity by ultrasonography and its relation to insulin resistance in HCV patients

Hepatitis C is a major cause of liver-related morbidity and mortality and represents a major public health problem in Egypt and worldwide, Ultrasonography is a simple non-invasive method for detection of visceral fat, which is directly, correlated with insulin resistance [IR] as well as development of type 2 diabetes mellitus. To assess the validity of detection of visceral adipose tissue area with Ultrasonography and its correlation with IR in HCV patients. The study participants were subcategorized into two groups, Group [I]: included 867 healthy subjects with negative [HCV] RNA as a control group. Group [II]: included 277 patients with chronic HCV as a study group. The 2 groups were subjected to thorough history taking, full clinical examination, Anthropometric study,ultrasonographic examination and laboratory investigations including liver functions, viral markers, and qualitative PCR for HCV RNA ,lipid profile and glucose profile. This study revealed that Ultrasonography is a simple, non-invasive, safe method in detection of visceral adiposity, which is correlated significantly with IR in chronic HCV patients

Prevención del síndrome metabólico en adolescentes

La resistencia a la insulina, según investigaciones internacionales, es cada vez más frecuente. Se le ha asociado con la etiología de la diabetes mellitus tipo 2, dislipidemia y otros factores de riesgo coronario. El objetivo primordial de este estudio es demostrar la importancia de la prevención del síndrome metabólico en adolescentes. Para ello se escogió intencionalmente una muestra de 70 estudiantes de un liceo de la ciudad de Valencia, ubicado en una zona de condición socioeconómica media o baja, que tuvieran antecedentes familiares de obesidad, diabetes, dislipidemia y enfermedad coronaria. En este grupo se encontró un 34 por ciento con colesterol elevado, un 26 por ciento con insulina elevada, 41 por ciento de lipoproteínas de baja densidad elevadas y un 17,14 por ciento con índice de masa corporal elevado (sobrepeso y obesidad). Con este grupo (12 casos) se puso en práctica un tratamiento a base de ejercicios de una hora interdiaria, dieta hipograsa y baja en carbohidratos durante 6 meses. Al finalizar el tiempo de tratamiento se encontró que todos los niveles medidos (peso real, índice de masa corporal, insulina, colesterol total, lipoproteínas de baja y alta densidad) mejoraron significativamente (P< 0,05). Este estudio demuestra la importancia que tiene poner en práctica tratamientos adecuados que ayuden a los adolescentes a enfrentar exitosamente la resistencia a la insulina y así prevenir el síndrome metabólico

The insulin resistance, according to international studies, is everyday more frequent. It has been associated with the etiology of diabetes mellitus type 2, dyslipidemia and other coronary factors. One of the principal objectives of this study is to determine the importance of the prevention of the metabolic syndrome in adolescents. A group of 70 adolescents were selected intentionally from a secondary school in Valencia city, located in a place of medium or low socioeconomic condition, in families with obesity, diabetes mellitus, dyslipidemia and coronary disease antecedents. It was found 34 percent with high total cholesterol levels, 26 percent with high insulin levels, 41 percent with high low density lipoproteins levels and 17.14 percent with high mass corporal index (overweight and obesity). This group of 12 cases received a low fat and low carbohydrates diet and practice exercise during one hour every two days for 6 months. After this time has elapsed they were evaluated again, finding that all levels (real weight, mass corporal index, insulin, total cholesterol, high and low density lipoproteins) were significative better (P<0.05). This study shows the importance of the application of suitable treatments that helps teenagers to confront successfully the insulin resistance and prevent the metabolic syndrome

Resistência insulínica imunológica: apresentação de caso / Immunologic insulin resistance: case report

Resistência insulínica imunológica é uma entidade reconhecida na prática clínica há muitos anos. Sua patogênese está relacionada ao aparecimento de anticorpos anti-insulina, e o tratamento baseia-se em imunossupressão. Apresentamos aqui o caso de uma paciente de 33 anos, com diagnóstico de diabetes desde a infãncia, que referia uso de hipoglicemiantes orais durante a adolescência. Durante o acompanhamento em nosso serviço, a dose de insulina foi progressivamente reduzida até ser substituída por hipoglicemiantes orais. Permaneceu 11 meses com esquema de glibenclamida, mefformina e acarbose até ser internada em coma hiperosmolar não-cetótico. Após internação prolongada, recebeu alta usando insulina NPH, sendo necessário o aumento da dose nos meses subseqüentes. Quando atingiu a dose de 2,7U/Kg/dia, foi investigada e excluída a possibilidade de diabetes secundário, sendo diagnosticada resistência insulínica imunológica. Foram tentados diversos esquemas imunossupressores sem sucesso. A paciente está atualmente em uso de bomba de infusão subcutânea de insulina Lispro, micofenolato mofetil e prednisona com melhora do controle glicêmico.

Diabetic ketoacidosis in adults: clinical and laboratory features

In this retrospective study, we report the clinical and biochemical features of diabetic ketoacidosis (DKA) in adult patients who were managed at the Instituto Nacional de la Nutricion during a 6.5 year period. There were 98 episodes in 46 patients: 22 females (48 per cent) and 24 males (52 per cent). Six patients (13 per cent) had four or more episodes of DKA were the initial manifestation of diabetes. We compared our results with those from other reported series, finding no differences among them. The mean anion gap in our series was 30.4. Main complications identified were hypokalemia in five cases, hypoglycemia in four cases hypernatremia in four cases, and acute pulmonary edema, ventricular fibrillation, neurological deficit and coma in one case each. There were three death (6.5 per cent) in the whole group. To our knowledge, this is the largest series on adult patients with DKA reported in our country in the last decade. The obtained results may help evaluate prospectively the impact of different diagnostic and therapeutic strategies in the management of DKA

Marcadores inmunológicos y de secreción insulínica en pacientes diabéticos no insulino dependientes con fracaso secundario a drogas hipoglicemiantes orales / Immunologic and insulin secretion markers in diabetic non insulin dependent patients with secondary failure to oral hypoglycemic agents

The pathogenesis of secondary failure to hypoglycemic agents is heterogenous. Some patients are true insulin dependent diabetics with a slow autoimmune disease suggested by their positive islet cell antibodies. Others, have an increased insulin resistance. To assess the frequency of positive islet cell antibodies in diabetic patients with secondary failure to oral hypoglycemic agents. 31 diabetics, 16 with recent (less than six months) secondary failure and 15 with metabolically stable non insulin dependent diabetes were studied. All patients were older than 25 years old and had a body mass index of less than 30 kg/m2. C peptide levels before and at 5,15 and 30 min after IV glucagon, islet cell antibodies using the Poly Human IgG peroxidase method an insulin sensitivity and secretion (estimated by the Homeostasis Model Assessment) were measured. Patients with secondary failure had lower C peptide levels compared to subjects with stable diabetes (basal: 1.5ñ0.2 and 2.8ñ0.2 ng/ml; 5 min: 2.4ñ0.3 and 5.5ñ0.5 ng/ml; 15 min:1.9ñ0.3 and 4.0ñ0.6 ng/ml; 30 min:1.6ñ0.3 and 3.4ñ0.5 ng/ml). Beta cell activity was 20.6ñ4.3 percent in patients with secondary failure and 92.2ñ9 percent in stable diabetics (p<0.01). Insulin sensitivity was similar in both groups (48.6ñ6 and 42.8ñ3.5 percent respectively). Three patients with secondary failure and none with stable diabetes had positive islet cell antibodies. When comparing patients with secondary failure and positive antibodies and subjects with secondary failure and negative antibodies, the former had non significantly lower age, BMI and C peptide levels. Some diabetic patients with secondary failure have positive islet cell antibodies. They should be measured in these patients to start insulin treatment precociously