Regulatory effects and mechanisms of branched chain amino acids and metabolic intermediates on insulin resistance / 生理学报

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and β-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. β-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.

Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation / 医学前沿

Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

Validity and reliability of simple surrogate indexes to evaluate beta-cell function and insulin sensitivity

BACKGROUND: Simple surrogate indexes (SSI) to assess beta-cell function, insulin sensitivity (IS) and insulin resistance (IR) are an easy and economic tool used in clinical practice to identify glucose metabolism disturbances. AIM: To evaluate the validity and reliability of SSI that estimate beta-cell function, IS and IR using as a reference the parameters obtained from the frequently sampled intravenous glucose tolerance test (FSIVGTT). MATERIAL AND METHODS: We included 62 subjects aged 20-45 years, with a normal body mass index and without diabetes or prediabetes. SSI were compared with the acute insulin response to glucose (AIRg), insulin sensitivity index (Si) and disposition index (DI) obtained from the FSIVGTT using the minimal model approach. Half of the participants (n = 31) were randomly selected for a second visit two weeks later to evaluate the reliability of all the variables. RESULTS: HOMA1-%B and HOMA2-%B had a significant correlation with AIRg (Spearman Rho (rs) = 0.33 and 0.37 respectively, p 0.50) with Si were fasting insulin, HOMA1-IR, HOMA2-IR, HOMA1-%S, HOMA2-%S, QUICKI, and the McAuley index. The parameters that showed good reliability with an intraclass correlation coefficient (ICC) > 0.75 were AIRg, HOMA1-%S, HOMA2-%S, and QUICKI. Conclusions: Our results suggest that most of the SSI are useful and reliable.

ANTECEDENTES: Los índices simples subrogados (ISS) que evalúan la función de célula beta, sensibilidad a la insulina (SI) y resistencia a la insulina (RI) son herramientas sencillas y económicas que se usan en la práctica clínica para identificar alteraciones del metabolismo de la glucosa. OBJETIVO: Evaluar la validez y confiabilidad de ISS para estimar la función de célula beta, SI y RI usando como referencia los parámetros de la prueba de tolerancia a la glucosa intravenosa con muestreo frecuente (FSIVGTT). MATERIAL Y MÉTODOS: Se incluyeron 62 sujetos de 20-45 años, con índice de masa corporal normal y sin diabetes mellitus o prediabetes. Los ISS se compararon con la respuesta aguda de la insulina a la glucosa (AIRg), índice de sensibilidad a la insulina (Si) e índice de disposición (DI) obtenidos de la FSIVGTT en base al modelo mínimo. La mitad de los participantes (n = 31) se seleccionaron aleatoriamente para acudir dos semanas después y evaluar la confiabilidad de todas las variables. RESULTADOS: HOMA1-%B y HOMA2-%B presentaron una correlación significativa con AIRg (Rho de Spearman (rs) = 0,33 and 0,37, respectivamente, p 0,50) con Si fueron insulina en ayuno, HOMA1-IR, HOMA2-IR, HOMA1-%S, HOMA2-%S, QUICKI y el índice de McAuley. Los parámetros que tuvieron buena confiabilidad (coeficiente de correlación intraclase > 0,75) fueron AIRg, HOMA1-%S, HOMA2-%S y QUICKI. Conclusiones: La mayoría de los ISS son instrumentos útiles y confiables.

Perfil dos pacientes com hiperferritinemia em acompanhamento ambulatorial em um serviço no sul do Brasil / Profile of patients with hyperferritinemia in ambulatorial follow-up in southern Brazil

O achado de hiperferritinemia é comum na prática clínica. Além de representar os estoques de ferro no organismo, a ferritina se mostra como proteína de fase inflamatória, podendo elevar-se em comorbidades inflamatórias agudas ou crônicas e se associar com a chamada síndrome plurimetabólica. Objetivo: Avaliar as características clínicas de pacientes com hiperferritinemia em acompanhamento ambulatorial no período de janeiro de 2013 a novembro de 2016. Métodos: Estudo observacional transversal, desenvolvido em um serviço de Hematologia na cidade de Tubarão, Santa Catarina. Coletaram-se dados de 136 pacientes com o diagnóstico de hiperferritinemia através de prontuários digitais. Foram realizadas análises descritivas e associações com os testes qui-quadrado e t Student, quando apropriado. Resultados: Houve um predomínio do sexo masculino (83,50%) com idade média de 56,62 anos, a média de ferritina de 693,45mcg/L e de ferro sérico 121,52mcg/dL, sendo as causas secundárias de hiperferritinemia as predominantes. Ao se estratificar os valores de ferritina constatou-se que os pacientes com ferritina >1000mcg/L tiveram um risco 50% maior de possuir alterações ao ultrassom, 70% maior prevalência de HDL<40 e 40% maior prevalência de hipertrigliceridemia. Os pacientes com ferritina >400mcg/L tiveram duas vezes maior chance de apresentar resistência à insulina. Conclusão: As principais causas de hiperferritinemia foram secundárias a doenças crônicas metabólicas

Hyperferritinemia is common in the clinical practice. In aside from representing the stocks of iron in the organism, ferritin is also a inflammatory phase protein, witch can be elevated in chronic or acute inflammatory comorbidities and be associated with plurimetabolic syndrome. This study aims the evaluation of the clinical characteristics of ambulatory patients with hyperferritinemia between January-2013 and November-2016. Methods: It is a cross-sectional, descriptive study, developed in the hematology center of the medical specialities clinic in Tubarão ­ Santa Catarina. Data from 136 patients have been collected and then transferred to an Excel spreadsheet, imported to Epiiinfo 7 and the expressed into absolute and relative numbers, graphics and figures. Results: It was found a predominance of males (83,50%) with a mean age of 56,62 years, a mean ferritin level of 693,45mcg/L and seric iron of 121,52mcg/dL being the secondary causes of hyperferritinemia the most predominant. When stratified the ferritin levels, it was verified that patients with a ferritin >1000mcg/L had 50% more risk of having ultrasound alterations, 70% more prevalence of HDL<40 and 40% more prevalence of having hypertriglyceridemia. Patients with a ferrintin >400mcg/L had twice as many chances of having insulin resistance. Conclusion: The main causes of hyperferritinemia were secondary to chronic metabolic diseases

Adiposidad abdominal y resistencia a la insulina al finalizar el primer trimestre de la gestación / Abdominal Adiposity and Insulin Resistance at the End of the First Trimester of Gestation

Introducción: La adiposidad central como factor desencadenante de resistencia a la insulina precoz constituye una amenaza potencial de riesgo metabólico y cardiovascular en el embarazo. Objetivo: Determinar la capacidad discriminante de las grasas abdominales sobre la resistencia a la insulina, diagnosticada por el índice triglicéridos/glucosa-IMC al finalizar el primer trimestre del embarazo. Métodos: Se realizó un estudio observacional analítico de 526 gestantes con embarazo simple y edad gestacional entre 12 y 13 semanas, entre los años 2016 y 2020. Se estudió el test de triglicéridos/glucosa-IMC y las grasas abdominales por ultrasonido. Se utilizaron las curvas ROC (Receiver operating characteristic Curve) para discriminar la resistencia a la insulina al finalizar el primer trimestre de la gestación, cuando aumentan las grasas abdominales. Resultados: La grasa subcutánea fue la que presentó mayor área bajo la curva en la discriminación de la resistencia a la insulina, con un nivel de sensibilidad y especificidad aceptable. Conclusiones: La grasa subcutánea, aunque con bajo valor discriminativo, puede considerarse como augurio de resistencia a la insulina y de diabetes gestacional. Se requiere profundizar en el estudio de las grasas abdominales dado el conocimiento de su impacto en los desórdenes metabólicos en el curso avanzado de la gestación(AU)

Introduction: Central adiposity as a triggering factor for early insulin resistance is a potential threat of metabolic and cardiovascular risk in pregnancy. Objective: To determine the discriminating capacity of abdominal fat over insulin resistance, diagnosed by the triglyceride/glucose-BMI index at the end of the first trimester of pregnancy. Methods: An analytical and observational study was carried out with 526 pregnant women of singleton pregnancy and gestational age between twelve and thirteen weeks, between 2016 and 2020. The triglyceride/glucose-BMI test was studied, together with abdominal fats by ultrasound. ROC (receiver operating characteristic) curves were used to discriminate insulin resistance at the end of the first trimester of gestation, when abdominal fats increase. Results: Subcutaneous fat presented the highest area under the curve in the discrimination of insulin resistance, with an acceptable level of sensitivity and specificity. Conclusions: Subcutaneous fat, although with low discriminative value, can be considered as a harbinger of insulin resistance and gestational diabetes. Further study of abdominal fat is required, given the knowledge of its impact on metabolic disorders in late gestation(AU)

Dimorfismo sexual de la leptina, resistencia a la insulina y composición corporal en prepúberes normopeso / Leptin sexual dimorphism, insulin resistance, and body composition in normal weight prepubescent

INTRODUCCIÓN: La etapa prepuberal es un periodo crítico del desarrollo de la grasa corporal, en el cual la leptina y la resistencia a la insulina han sido asociados, sin embargo, hay pocos estudios en prepúberes normo- peso. OBJETIVO: Evaluar la relación de leptina con composición corporal y resistencia a la insulina en un grupo de prepúberes normopeso. PACIENTES Y MÉTODO: Estudio transversal analítico en 128 pre púberes saludables, normopeso, entre 6 y 10 años. Se midieron, talla, peso, índice de masa corporal (IMC), porcentaje de grasa corporal (PGC), perímetro abdominal (PA) y perímetro de cadera (PC). Se determinó leptina (ng/ml) e Insulina (μU/L) en plasma por inmunoensayo y glicemia (mmol/L) por método enzimático. Se calculó HOMA-IR. Se hizo análisis de comparación y de correlación por sexo. RESULTADOS: Se confirmó en niñas un mayor nivel de leptina (6,8 ± 5 vs 3,3 ± 3,7; p = 0,000), insulina (7,1 ± 4,5 vs 5,2 ± 2,5; p = 0,016), PGC (22,4 ± 4,3 vs 18,6 ± 3,9; p = 0,000) y PC (67 ± 5,7 vs 65,0 ± 4,5; p = 0,019), y un menor índice cintura/cadera (0,84 ± 0,04 vs 0,88 ± 0,04; p = 0,000) comparado con varones. Las correlaciones de leptina con variables antropométricas fueron signifi cantes en ambos sexos, con mayor asociación en sexo femenino. La asociación del HOMA-IR con la leptina fue similar en ambos sexos. CONCLUSIONES: En prepúberes normopeso de 6 a 10 años, hay diferencias por sexo en adiposidad y en niveles de leptina, no asociadas con diferencias en el IMC ni en la resistencia a la insulina. La mayor asociación de leptina con adiposidad en las niñas podría estar relacionada con una elevada tasa de adipogénesis inducida por esta hormona.

INTRODUCTION: The prepubertal stage is a critical period of body fat development, in which leptin and insulin re sistance has been associated, however, there are few studies in normal-weight prepubescents. OBJECTIVE: To assess the relationship between leptin and body composition and insulin resistance in a group of normal-weight prepubescents. PATIENTS AND METHOD: Analytical cross-sectional study with 128 healthy prepubescents of normal weight, aged between 6 and 10 years. Height, weight, body mass index (BMI), body fat percentage (BFP), waist circumference (WC), and hip circumference (HC) were measured. Plasma leptin (ng/mL) and insulin (mU/L) were evaluated by immunoassay and glycemia (mmol/L) by enzymatic method. HOMA-IR was calculated. A comparison study and correlation analysis by sex were performed. RESULTS: Females presented higher values than males of leptin (6.8 ± 5 vs 3.3 ± 3.7; p = 0.000), insulin (7.1 ± 4.5 vs 5.2 ± 2.5; p = 0.016), BFP (22.4 ± 4.3 vs 18.6 ± 3.9; p = 0.000), and HC (67 ± 5.7 vs 65.0 ± 4.5; p = 0.019), and a lower waist/hip ratio (0.84 ± 0.04 vs 0.88 ± 0.04; p = 0.000). Leptin correlations with anthropometric variables were significant in both sexes, with greater association in females. The association of HOMA-IR with leptin was similar in both sexes. CONCLUSIONS: in normal-weight prepubescents aged between 6-10 years, there are sex differences in adiposity and leptin levels not associated with differences in BMI or insulin resistance. The greater association of leptin with adiposity in girls could be related to a high rate of adipogenesis induced by this hormone.

Índice glucosa-triglicéridos como marcador de resistencia a la insulina en pacientes con diagnóstico de hipertensión arterial esencial / Glycemia-triglyceride index as marker of insulin resistance in essential hypertensive patients

Introducción: El índice glucemia-triglicéridos se utiliza para el diagnóstico presuntivo de la resistencia insulínica, que en los pacientes hipertensos se relaciona con la severidad de la hipertensión arterial. Objetivo: Determinar la utilidad del índice glucemia-triglicéridos como marcador de resistencia a la insulina en pacientes adultos con diagnóstico de hipertensión arterial esencial. Métodos: Se realizó un estudio descriptivo transversal en 232 pacientes con diagnóstico de hipertensión arterial esencial. Se calculó el índice glucemia-triglicéridos y se comparó con el índice HOMA. Para este análisis se utilizó la curva ROC, la correlación de Pearson y el Índice de Kappa, se consideró significativo un valor de p menor a 0,05. Resultados: Se obtuvo un punto de corte de 8,1 que mostró una sensibilidad de 98,6 con una especificidad de 41,4. La curva ROC mostró un área bajo la curva con valor de 0,694 ≈ 0,7. Se observó correlación positiva (p=0,008) Índice de Kappa=88,4 por ciento. Conclusiones: El índice glucemia-triglicéridos resulto ser útil en pacientes con hipertensión arterial como marcador de resistencia a la insulina con un punto de corte de 8,1(AU)

Introduction: The glycemia-triglyceride index is used for the presumptive diagnosis of insulin resistance, which in hypertensive patients is related to the severity of high blood pressure. Objective: To determine the utility of the glycemia-triglyceride index as a marker of insulin resistance in adult patients diagnosed with essential arterial hypertension. Methods: A descriptive cross-sectional study was carried out in 232 patients diagnosed with essential arterial hypertension. The glycemia-triglyceride index was calculated and compared with HOMA index. For this analysis, ROC curve, Pearson correlation and Kappa index were used, p value less than 0.05 was considered significant. Results: We obtained an 8.1 cut-off point, showing 98.6 sensitivity and 41.4 specificity. The area below the ROC curve showed 0.694 ≈ 0.7 value. Positive correlation was observed (p = 0.008). Kappa index = 88.4 percent. Conclusions: The glycemia-triglyceride index turned out to be useful in patients with essential hypertension as a marker of insulin resistance with a cut-off point of 8.1(AU)

Relationships among oncostatin M, insulin resistance, and chronic inflammation: a pilot study

ABSTRACT Objective Activated macrophages (M1-type macrophages) in adipose tissue secrete many proinflammatory cytokines that induce insulin resistance (IR). Oncostatin M (OSM), a member of the interleukin-6 (IL-6) family of Gp130 cytokines, plays an important role in a variety of biological functions, including the regulation of inflammatory responses. Proinflammatory cytokines released in patients with IR trigger a chronic, low-grade inflammatory reaction in blood vessel walls. This inflammator response leads to endothelial damage, which is the main mechanism for atherosclerosis and many cardiovascular diseases. Animal studies have reported a relationship between OSM and IR. To the best of our knowledge, however, few clinical studies have examined this topic. Therefore, we studied the relationship between serum levels of OSM and IR. Subjects and methods This prospective cross-sectional case-control study enrolled 50 people with IR (according to the HOMA-IR and QUICKI indices) and 34 healthy controls. The fasting blood concentrations of insulin, glucose, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, total cholesterol, C-reactive protein (CRP), and OSM were determined. Results There were no significant differences between the two groups in age, sex, and HbA1c levels. Univariate analyses showed that waist circumference (WC) and levels of fasting glucose, insulin, CRP, HDL-C, OSM, HOMA-IR, and QUICKI differed between the two study groups. In multivariate analyses, both IR indices (QUICKI and HOMA) and OSM differed between the two groups. Conclusion OSM was correlated with the IR indices (QUICKI and HOMA). For simplicity, it might replace the other IR indices in the future. Further detailed studies are needed to confirm this.

NLRP3 inflammasome in metabolic syndrome

Metabolic syndrome (MS) is a serious health problem worldwide; it is characterized by a group of metabolic disorders, including central obesity, insulin resistance/type 2 diabetes, hyperlipidemia with accelerated atherosclerosis, hypertension, non-alcoholic fatty liver disease, and elevated uric acid with increased risk of gout. The incidence of MS has increased considerably in recent decades and has attracted considerable attention. A number of clinical and translational laboratory studies have implicated the activation of nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in the development of MS, therefore establishing a strong link between chronic inflammation and metabolic diseases. This paper aims to review new developments on NLRP3 inflammasome in MS for better understanding of chronic inflammation in metabolic diseases. We will also provide new insights into using NLRP3 inflammasome as an innovative therapeutic target.

Muscular resistance, hypertrophy and strength training equally reduce adiposity, inflammation and insulin resistance in mice with diet-induced obesity / Exercícios físicos de resistência, hipertrofia e força muscular reduzem igualmente adiposidade, inflamação e resistência à insulina em camundongos obesos por dieta hiperlipídica

ABSTRACT Objective To evaluate the effect of three types of muscular resistance training on adiposity, inflammation levels and insulin activity in Swiss mice with fat-rich diet-induced obesity. Methods Lean and obese male Swiss mice were selected and allocated to one of eight groups comprising eight mice each, as follows: standard diet + no training; standard diet + muscular resistance training; standard diet + hypertrophy training; standard diet + strength training; high-fat diet + no training; high-fat diet + muscular resistance training; high-fat diet + hypertrophy training; high-fat diet + strength training. The training protocol consisted of stair climbing for a 10-week period. Blood samples were collected for lactate analysis, glucose level measurement and insulin tolerance test. After euthanasia, adipose tissues were removed and weighed for adiposity index determination. Fragments of epididymal adipose tissue were then embedded for histological analysis or homogenized for tumor necrosis factor alpha level determination using the ELISA method. Results Ausency of differences in total training volume and blood lactate levels overall emphasize the similarity between the different resistance training protocols. Body weight loss, reduced adipocyte area and lower adiposity index were observed in trained obese mice, regardless of training modality. Different training protocols also improved insulin sensitivity and reduced inflammation levels. Conclusion Resistance training protocols were equally effective in reducing body fat, inflammation levels and insulin resistance in obese mice.

RESUMO Objetivo Avaliar os efeitos de três tipos de treinamentos de resistência na adiposidade, na inflamação e na ação da insulina em camundongos Swiss obesos por dieta hiperlipídica. Métodos Camundongos Swiss machos magros e obesos foram selecionados e posteriormente separados em oito grupos com oito animais em cada: dieta padrão + não treinado; dieta padrão + treinamento de resistência muscular; dieta padrão + treinamento de hipertrofia; dieta padrão + treinamento de força; dieta hiperlipídica + não treinado; dieta hiperlipídica + treinamento de resistência muscular; dieta hiperlipídica + treinamento de hipertrofia; e dieta hiperlipídica + treinamento de força. O protocolo de treinamento consistiu em escaladas, por um período de 10 semanas. Amostras de sangue foram coletadas para análises de lactato, glicemia e teste de tolerância à insulina. Após eutanásia, os tecidos adiposos foram retirados e pesados para determinar o índice de adiposidade. Em seguida, parte do tecido adiposo epididimal foi emblocado para análises histológicas, e outra parte foi homogeneizada para análises de fator de necrose tumoral alfa por ELISA. Resultados O volume total de treinamento e a concentração sanguínea de lactato não diferiram entre os três treinos resistidos, sugerindo similaridade entre eles. Nos animais obesos, as três modalidades de treinamento reduziram o peso corporal, a área adipocitária e o índice de adiposidade. Os três tipos de treinamentos ainda melhoraram a tolerância à insulina e reduziram a inflamação. Conclusão Os protocolos de treinamento resistido foram igualmente efetivos em reduzir a adiposidade, a inflamação e a resistência à ação da insulina em camundongos obesos.

Reduction of oxidative stress improves insulin signaling in cardiac tissue of obese mice / Redução do estresse oxidativo melhora a sinalização da insulina em tecido cardíaco de camundongos obesos

ABSTRACT Objective To evaluate the effects of oxidative stress on insulin signaling in cardiac tissue of obese mice. Methods Thirty Swiss mice were equally divided (n=10) into three groups: Control Group, Obese Group, and Obese Group Treated with N-acetylcysteine. After obesity and insulin resistance were established, the obese mice were treated with N-acetylcysteine at a dose of 50mg/kg daily for 15 days via oral gavage. Results Higher blood glucose levels and nitrite and carbonyl contents, and lower protein levels of glutathione peroxidase and phosphorylated protein kinase B were observed in the obese group when compared with their respective control. On the other hand, treatment with N-acetylcysteine was effective in reducing blood glucose levels and nitrite and carbonyl contents, and significantly increased protein levels of glutathione peroxidase and phosphorylated protein kinase B compared to the Obese Group. Conclusion Obesity and/or a high-lipid diet may result in oxidative stress and insulin resistance in the heart tissue of obese mice, and the use of N-acetylcysteine as a methodological and therapeutic strategy suggested there is a relation between them.

RESUMO Objetivo Avaliar os efeitos do estresse oxidativo sobre a sinalização da insulina em tecido cardíaco de camundongos obesos. Métodos Utilizaram-se 30 camundongos Swiss subdivididos igualmente (n=10) em três grupos: Grupo Controle, Grupo Obeso e Grupo Obeso Tratado com N-acetilcisteína. Após estabelecidas a obesidade e a resistência à insulina, os camundongos obesos foram tratados diariamente, durante 15 dias, via gavagem oral, com N-acetilcisteína na dose de 50mg/kg. Resultados Observaram-se maiores níveis de glicose sanguínea, conteúdos de nitrito e carbonil, e menores níveis proteicos de glutationa peroxidase e proteína quinase B fosforilada no Grupo Obeso quando comparado a seu respectivo controle. Por outro lado, o tratamento com N-acetilcisteína se mostrou eficiente em diminuir os níveis glicêmicos, os conteúdos de nitrito e carbonil, e aumentar significativamente os níveis proteicos de glutationa peroxidase e proteína quinase B fosforilada, quando comparados ao Grupo Obeso. Conclusão Obesidade e/ou dieta hiperlipídica levam a estresse oxidativo e à resistência à insulina no tecido cardíaco de camundongos obesos, e o uso da N-acetilcisteína como estratégia metodológica e terapêutica sugeriu haver relação entre ambos.

Insulin resistance is associated with Sfrp5 in obstructive sleep apnea / Resistência à insulina está associada à Sfrp5 na apneia obstrutiva do sono

Abstract Introduction: Obstructive sleep apnea, a common disease, is usually complicated by insulin resistance and type 2 diabetes mellitus. Adipokine is considered to play an important role in the development of insulin resistance and type 2 diabetes mellitus in obstructive sleep apnea. Objective: To assess whether secreted frizzled-related protein 5, a new adipokine, is involved in untreated obstructive sleep apnea patients. Methods: Seventy-six subjects with obstructive sleep apnea and thirty-three control subjects without obstructive sleep apnea were recruited and matched in terms of body mass index and age. The fasting secreted frizzled-related protein 5 plasma concentration was tested using ELISA. In addition, the correlation between secreted frizzled-related protein 5 and the homeostasis model assessment of insulin resistance was obtained. Multiple linear regression analysis models with stepwise selection were performed to determine the independent associations between various factors and secreted frizzled-related protein 5. Results: Plasma secreted frizzled-related protein 5 levels were significantly lower in the obstructive sleep apnea group than in the control group (obstructive sleep apnea group: 28.44 ± 13.25 ng/L; control group: 34.16 ± 13.51 ng/L; p = 0.023). In addition, secreted frizzled-related protein 5 was negatively correlated with homeostasis model assessment of insulin resistance but positively correlated with the mean and lowest oxygen saturation with or without adjusting for age, gender, body mass index, neck circumference, waist circumference and waist-to-hip ratio. The multiple linear regression analysis showed there was an independent negative association between secreted frizzled-related protein 5 and homeostasis model assessment of insulin resistance. Conclusion: Secreted frizzled-related protein 5 was involved in obstructive sleep apnea and the decrease in secreted frizzled-related protein 5 was directly proportional to the severity of obstructive sleep apnea. There was an independent negative correlation between homeostasis model assessment of insulin resistance and secreted frizzled-related protein 5 in the obstructive sleep apnea group. Secreted frizzled-related protein 5 might be a therapeutic target for insulin resistance in obstructive sleep apnea.

Resumo Introdução: A apneia obstrutiva do sono, uma doença comum, é geralmente complicada com resistência à insulina e diabetes melito tipo 2. Acredita-se que a adipocina possa ter um papel importante no desenvolvimento de resistência à insulina e diabetes melito tipo 2 na apneia obstrutiva do sono. Objetivo: Avaliar se a proteína secretada relacionada ao receptor frizzled-5, uma nova adipocina, está envolvida em pacientes com apneia obstrutiva do sono não tratada. Método: Foram recrutados 76 indivíduos com apneia obstrutiva do sono e 33 indivíduos controle sem apneia obstrutiva do sono e pareados em relação a índice de massa corporal e idade. A concentração plasmática de proteína secretada relacionada ao receptor frizzled-5 foi testada em jejum com o teste Elisa. Além disso, obteve-se correlação entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Modelos de análise de regressão linear múltipla com seleção stepwise foram feitos para determinar as associações independentes entre vários fatores e a proteína secretada relacionada ao receptor frizzled-5. Resultados: Os níveis plasmáticos de proteína secretada relacionada ao receptor frizzled-5 foram significativamente menores no grupo com apneia obstrutiva do sono do que no grupo controle (grupo com apneia obstrutiva do sono: 28,44 ± 13,25 ng/L; grupo controle: 34,16 ± 13,51 ng/L; p = 0,023). Além disso, a proteína secretada relacionada ao receptor frizzled-5 foi correlacionada negativamente com o modelo de avaliação da homeostase de resistência à insulina, mas se correlacionou positivamente com a média e a saturação mínima de oxigênio com ou sem ajuste para idade, gênero, índice de massa corporal, circunferência do pescoço, circunferência da cintura e relação cintura-quadril. A análise de regressão linear múltipla mostrou que houve uma associação negativa independente entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Conclusões: A proteína secretada relacionada ao receptor frizzled-5 esteve envolvida na apneia obstrutiva do sono e sua diminuição foi diretamente proporcional à gravidade da apneia obstrutiva do sono. Houve uma correlação negativa independente entre o modelo de avaliação da homeostase de resistência à insulina e a proteína secretada relacionada ao receptor frizzled-5 no grupo da apneia obstrutiva do sono. A proteína secretada relacionada ao receptor frizzled-5 pode ser um alvo terapêutico para a resistência à insulina na apneia obstrutiva do sono.

Insulin signaling in the whole spectrum of GH deficiency

ABSTRACT GH is one of the insulin counterregulatory hormones which acts in the opposite way to insulin, increasing the glucose production by the liver and kidneys and decreasing glucose uptake from peripheral tissues, thus being a hyperglycemic hormone. When in excess, as in acromegaly, it induces glucose intolerance and diabetes. As expected, patients with GH deficiency (GHD) have hypoglycemia, especially in early childhood, but as GH is also a lipolytic hormone, these patients are becoming obese with higher percentages of body fat. Although obesity in general is directly related to insulin resistance, in patients with GH secretion disorders this relationship may be altered. In acromegaly there is a decrease in fat mass with worsening insulin sensitivity and mice with isolated GHD are characterized by greater insulin sensitivity despite excess fat mass. In humans with GHD, body composition shows increased body fat and decreased free fat mass, but the results regarding insulin sensitivity are still controversial in these patients. These discrepant results regarding insulin sensitivity in patients with GHD suggest the existence of other variables influencing these results. In the present review, we will try to follow the path of the different researches conducted on this subject, both in animal and human models, with the goal of understanding the current knowledge of insulin sensitivity across the spectrum of GHD. Arch Endocrinol Metab. 2019;63(6):582-91

The relationships between hemoglobin and insulin resistance, glucose effectiveness, and first- and second-phase insulin secretion in adult Chinese

ABSTRACT Objective We denote the four major factors related to the development of type 2 diabetes (T2D) as "diabetes factor" (DF); increased insulin resistance (IR); decreased glucose effectiveness (GE); and the first-and-second-phase of insulin secretion (FPIS, SPIS). The level of hemoglobin (Hb) was found to be related to IR and FPIS, but no-known studies focused on its role in relation to SPIS and GE. In this study, we aim to evaluate the relationships between Hb and all four DFs in the same individual. Subjects and methods We randomly enrolled 24,407 men and 24,889 women between 30 and 59 years old. IR, FPIS, SPIS and GE were measured according to equations published in our previous studies. To compare the slopes between Hb and the four DFs with different units, we converted their units to percent of change per unit of increased Hb. Results Age, HDL-cholesterol and GE were higher in women; BMI, blood pressure, LDL-cholesterol, TG, Hb, FPIS, SPIS and IR were higher in men. After they were converted into percentage, the closeness of their relationships to Hb, from the highest to the lowest, were GE, IR, FPIS and SPIS for women and IR, GE, FPIS and SPIS for men. GE was the only one negatively related to Hb. Conclusions Our data showed that IR, FPIS and SPIS were both positively and, GE negatively, related to the Hb in adult Chinese. For women, GE had the closest association with Hb; for men, it was IR. Both phases of insulin secretion had relatively weaker relationships than IR and GE.

Soluble insulin receptor and metabolic syndrome

The metabolic syndrome describes a group of signs that increase the likelihood for developing type 2 diabetes mellitus, cardiovascular diseases and some types of cancer. The action of insulin depends on its binding to membrane receptors on its target cells. We wonder if blood insulin could travel bound to proteins and if, in the presence of hyperinsulinemia, a soluble insulin receptor might be generated. We used young adult Wistar rats (which have no predisposition to obesity or diabetes), whose drinking water was added 20 % of sugar and that were fed a standard diet ad libitum for two and six months. They were compared with control rats under the same conditions, but that had running water for consumption. At two months, the rats developed central obesity, moderate hypertension, high triglyceride levels, hyperinsulinemia, glucose intolerance and insulin resistance, i.e., metabolic syndrome. Electrophoresis of the rats’ plasma proteins was performed, followed by Western Blot (WB) for insulin and for the outer portion of the insulin receptor. The bands corresponding to insulin and to the receptor external part were at the same molecular weight level, 25-fold higher than that of free insulin. We demonstrated that insulin, both in control animals and in those with hyperinsulinemia, travels bound to the receptor outer portion (ectodomain), which we called soluble insulin receptor, and that is released al higher amounts in response to plasma insulin increase; in rats with metabolic syndrome and hyperinsulinemia, plasma levels are much higher than in controls. Soluble insulin receptor increase in blood might be an early sign of metabolic syndrome.

Insulin-like growth factor binding protein-1, non-alcoholic fatty liver disease, and its relationship with fructose consumption in children with obesity

Background Over consumption of added sugar is associated with obesity, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR). Objective The objective of the study was to study the insulin-like growth factor binding protein-1 (IGFBP-1) and NAFLD and their relationship with fructose consumption in children with obesity. Methods A cross-sectional study was carried out in children 6-11 years old with obesity. Anthropometric measurements, fructose consumption, glucose, lipid profile, insulin, and IGFBP-1 levels were evaluated; the homeostatic model assessment of IR (HOMA-IR) was used. NAFLD was evaluated by ultrasound. Results We studied 83 children with a mean age of 9.2 ± 1.3 years. About 93% of the girls presented IR and lower levels of IGFBP-1 (p = 0.0001). The group with the lower levels of IGFBP-1 had higher HOMA-IR (p = 0.000002); IGFBP-1 was associated with fructose consumption (r = −0.25; p = 0.03), body mass index (BMI) (r=−0.42; p = 0.02), and HOMA-IR (r=−0.61; p = 0.002). About 81% of the children were classified as having mild or moderate/severe NAFLD, and these groups had higher HOMA-IR (p = 0.036) and fructose consumption (p = 0.0014). Conclusions The girls had more metabolic alterations. The group with lower levels of IGFBP-1 (hepatic IR) was associated with higher BMI, HOMA-IR, and fructose consumption; the group with higher severity of NAFLD showed higher HOMA-IR and fructose consumption.

Estudo de parâmetros metabólicos em pacientes não diabéticos com doença hepática gordurosa não alcoólica - importância da dislipidemia / A study of metabolic parameters in non diabetic patients with non alcoholic fatty liver disease - importance of dyslipidemia

ABSTRACT BACKGROUND: Metabolic risk factors of non alcoholic fatty liver disease (NAFLD) in non diabetic teetotallers who constitute a definite group are not well defined. OBJECTIVE: To identify the metabolic risk factors of NAFLD if any in non diabetic subjects who do not consume alcohol. METHODS: In a cross sectional study the effect of metabolic parameters (BMI, individual lipid levels, hemoglobinA1c (HbA1c), HOMA IR and the metabolic syndrome components) of 150 consecutive non diabetic teetotallers (90 with normal glucose tolerance and 60 prediabetics) on their NFS (quantifiable severity parameter of NAFLD) was studied by linear regression analysis. Similar study was done in the normal glucose tolerance and prediabetes groups separately. These parameters were then compared with those of 75 matched diabetic teetotallers with NAFLD. To analyse further the difference between normal glucose tolerance, prediabetic and overt diabetic groups, binary logistic regression of the factors was carried out taking prediabetes and diabetes as outcome variable. RESULTS: All the metabolic parameters were significantly higher in diabetics compared to non diabetics and in prediabetics compared to those with normal glucose tolerance except high-density lipoprotein cholesterol. Triglyceride, high-density lipoprotein cholesterol and BMI significantly predicted NFS in the overall (adjusted R2 68.7%, P=0.000) and normal glucose tolerance groups (adjusted R2 73.2%, P=0.000) whereas BMI, triglyceride, low-density lipoprotein cholesterol and HbA1c did in prediabetics (adjusted R2 89%, P=0.000). The metabolic syndrome was significantly associated with NFS in the overall and prediabetic groups. High triglyceride (odds ratio1.08), low-density lipoprotein cholesterol (odds ratio1.03) and HbA1c (odds ratio 11.54) were positively associated with prediabetes compared to normal glucose tolerance group. CONCLUSION: In nondiabetic teetotallers dyslipidemias are the prime contributors to the development of NAFLD.

RESUMO CONTEXTO: Os fatores de risco metabólicos da doença hepática gordurosa não alcoólica (DHGNA) em abstêmios não diabéticos, que constituem um grupo distinto, não são bem definidos. OBJETIVO: Identificar os fatores de risco metabólicos da DHGNA em indivíduos não diabéticos e que não consumam álcool. MÉTODOS: Em um estudo transversal, o efeito dos parâmetros metabólicos (IMC, níveis de lipídios individuais, HbA1c, Homa IR e os componentes da síndrome metabólica) de 150 abstêmios não diabéticos consecutivos (90 com tolerância à glicose normal e 60 pré-diabéticos) em sua NFS (parâmetro de gravidade quantificável da DHGNA) foram estudados por análise de regressão linear. Um estudo similar em separado foi feito nos grupos normais da tolerância da glicose e do pré-diabetes. Esses parâmetros foram comparados com os de 75 abstêmios diabéticos pareados com DHGNA. Para analisar ainda mais a diferença entre a tolerância à glicose normal foi realizada a regressão logística binária dos fatores tomando pré-diabetes e diabetes como variável de desfecho, nos grupos diabéticos e pré-diabéticos. RESULTADOS: Todos os parâmetros metabólicos foram significativamente maiores nos diabéticos comparados aos não diabéticos e em pré-diabéticos comparados àqueles com tolerância normal à glicose, exceto HDL. Os índices TG, HDL e IMC previram significativamente o NFS no geral nos grupos de tolerância normal (R2 ajustado 68,7%, P=0,000) e de glicose normal (R2 ajustado 73,2%, P=0,000), enquanto o IMC, TG, LDL e HbA1c predisseram em pré-diabéticos (R2 ajustado 89%, P=0,000). A síndrome metabólica foi associada significativamente com o NFS nos grupos totais e pré-diabéticos. O TG elevado (odds ratio 1,08), o LDL (odds ratio 1,03) e a HbA1c (odds ratio 11,54) foram positivamente associados ao pré-diabetes em comparação com o grupo normal de tolerância à glicose. CONCLUSÃO: Em abstêmios não diabéticos as dislipidemias são os principais contribuintes para o desenvolvimento da DHGNA.

Non-alcoholic fatty pancreatic disease and insulin resistance: overlooked complication of obstructive sleep apnea and hypopnea syndrome - signaling pathway diagram / Doença pancreática gordurosa não alcoólica e resistência insulínica: complicação negligenciada da síndrome de apneia e hipopneia obstrutiva do sono

Objective: To demonstrate the interaction between obstructive sleep apnea/hypopnea syndrome, insulin resistance, and non-alcoholic fatty pancreatic disease through the signaling pathway diagram. Methods: To investigate the involvement of metabolic signaling pathway, a search was performed using the Kyoto Encyclopedia of Genes and Genomes. The signaling pathway mapping was performed using the automatic annotation server of this encyclopedia. The Modeller 9.19 package was used to predict 3-dimensional structures based on the homology modeling protocol. The signaling pathway map was performed using PathVisio software, which is a free available signaling pathway drawing software. Based on the 3-dimensional structures, we have designed several peptide activators of the signaling pathway of non-alcoholic fatty pancreatic disease. Results: The contigs were taken from the Kyoto Encyclopedia of Genes and Genomes database and their mapped transcription represented the signaling pathway of the main biomolecules that triggered non-alcoholic fatty pancreatic disease. The interaction between obstructive sleep apnea/hypopnea syndrome, insulin resistance, and inflammatory factors contributes to the possible development of fatty infiltration of pancreas, leading to the loss of function of the pancreatic ß-cells, and even to the development of other metabolic diseases. Conclusion: The interaction between obstructive sleep apnea/hypopnea syndrome and insulin resistance demonstrated through the signaling pathway contributes to the possible development of non-alcoholic fatty pancreatic disease. (AU)

Objetivo: Demonstrar a interação entre a síndrome de apneia/ hipopneia obstrutiva do sono, a resistência à insulina e a doença pancreática gordurosa não alcoólica considerando o desenho de uma via de sinalização. Métodos: Para avaliar o envolvimento da via de sinalização metabólica, realizou-se uma pesquisa usando a Enciclopédia de Genes e Genomas de Kyoto. O mapeamento da via de sinalização foi realizado com o servidor de anotação automático desta enciclopédia. O software MODELLER 9.19 foi usado para prever estruturas tridimensionais, com base no protocolo de modelagem por homologia. O desenho da via de sinalização foi realizado por meio do programa PathVisio, um software de domínio público para desenho de via de sinalização. Com base nas estruturas tridimensionais, desenhamos os vários ativadores peptídicos da via de sinalização da esteatose pancreática. Resultados: Os contigs foram retirados do banco de dados da Enciclopédia de Genes e Genomas de Kyoto, e sua transcrição mapeada representou a via de sinalização das principais biomoléculas que desencadearam doença pancreática gordurosa não alcoólica. A interação entre síndrome de apneia/hipopneia obstrutiva do sono, resistência à insulina e fatores inflamatórios contribuiu para o possível desenvolvimento de infiltração gordurosa do pâncreas, levando à perda de função das células beta pancreáticas e até mesmo ao desenvolvimento de outras doenças metabólicas. Conclusão: A interação entre síndrome de apneia/hipopneia obstrutiva do sono e resistência à insulina demonstrada pela via de sinalização contribui para o possível desenvolvimento de doença pancreática gordurosa não alcoólica. (AU)

Waist-to-height ratio is as reliable as biochemical markers to discriminate pediatric insulin resistance / A razão cintura/estatura é tão confiável quanto marcadores bioquímicos para discriminar resistência à insulina

Abstract Objective: Given the importance of incorporating simple and low-cost tools into the pediatric clinical setting to provide screening for insulin resistance, the present study sought to investigate whether waist-to-height ratio is comparable to biochemical markers for the discrimination of insulin resistance in children and adolescents. Methods: This cross-sectional study involved students from nine public schools. In total, 296 children and adolescents of both sexes, aged 8 -14 years, composed the sample. Waist-to-height ratio, triglycerides/glucose index, and triglycerides-to-HDL-C ratio were determined according to standard protocols. Insulin resistance was defined as homeostatic model assessment for insulin resistance with cut-off point ≥ 3.16. Results: Age, body mass index, frequency of overweight, waist circumference, waist-to-height ratio, insulin, glucose, homeostatic model assessment for insulin resistance, triglycerides, triglycerides/glucose index, and triglycerides-to-HDL-C were higher among insulin resistant boys and girls. Moderate correlation of all indicators (waist-to-height ratio, triglycerides/glucose index, and triglycerides-to-HDL-C ratio) with homeostatic model assessment for insulin resistance was observed for both sexes. The areas under the receiver operational characteristic curves ware similar between waist-to-height ratio and biochemical markers. Conclusion: The indicators provided similar discriminatory power for insulin resistance. However, taking into account the cost-benefit ratio, we suggest that waist-to-height ratio may be a useful tool to provide screening for insulin resistance in pediatric populations.

Resumo Objetivo: Considerando a importância de incorporar ferramentas simples e de baixo custo no cenário clínico-pediátrico para a triagem de resistência à insulina, o presente estudo buscou investigar se a razão cintura/estatura é comparável a marcadores bioquímicos na discriminação de resistência à insulina em crianças e adolescentes. Métodos: Este estudo transversal envolveu estudantes de nove escolas públicas. No total, 296 crianças e adolescentes, de ambos os sexos, com idades entre 8 e 14 anos, compuseram a amostra. A razão cintura/estatura, o índice triglicerídeos/glicose e a razão triglicerídeos/HDL-C foram determinados de acordo com protocolos padrão. A resistência à insulina foi definida por meio do modelo de avaliação homeostática para resistência insulínica, com ponto de corte ≥ 3.16. Resultados: Idade, índice de massa corporal, frequência de excesso de peso, circunferência da cintura, razão cintura/estatura, insulina, glicemia, modelo de avaliação homeostática para resistência insulínica, triglicerídeos, índice triglicerídeos/glicose e razão triglicerídeos/HDL-C foram maiores entre meninos e meninas com resistência à insulina. Também foram observadas, em ambos os sexos, correlações moderadas de todos os indicadores (razão cintura/estatura, índice triglicerídeos/glicose e razão triglicerídeos/HDL-C) com o modelo de avaliação homeostática para resistência à insulina. As áreas sob as curvas ROC foram semelhantes entre a razão cintura/estatura e os marcadores bioquímicos. Conclusão: Os indicadores forneceram poder discriminatório similar para a resistência à insulina. No entanto, levando em conta o custo-benefício, sugerimos que a razão cintura/estatura pode ser uma ferramenta útil para a triagem de resistência à insulina em populações pediátricas.

Resistencia a la insulina en mujeres con síndrome de ovario poliquístico / Insulin resistance in women with polycystic ovary syndrome

RESUMEN Introducción: La resistencia a la insulina es frecuente en el síndrome de ovario poliquístico, con diferencias entre fenotipos y discrepancias sobre cómo medirla. Objetivo: Identificar trastornos de la sensibilidad y resistencia a la insulina en mujeres con síndrome de ovario poliquístico, y determinar si es mayor en el fenotipo clásico. Métodos: Incluyó 152 mujeres: 45 sin síndrome de ovario poliquístico (Grupo I); 46 con síndrome de ovario poliquístico clínico (Grupo II); 61 con síndrome de ovario poliquístico clásico (Grupo III). Se realizó prueba de tolerancia a la glucosa oral, se calcularon índices de sensibilidad o resistencia a la insulina en ayunas (HOMA-IR, I0/G0, FIRI, ISI, Belfiore, Bennet, Quicki, Raynaud) y en la prueba de tolerancia a la glucosa oral (Belfiore2, Ribel, Ins2glu2, ATI, IITotal, DATI/DATG, Matsuda, BetaHOMA). Se emplearon las pruebas de Kruskal-Wallis, Mann-Whitney y Chi cuadrado. Resultados: Las mujeres con síndrome de ovario poliquístico tenían más obesidad global y central (p / 0,05), más nivel de glucemia a los 30, 120 y 180 minutos de la prueba de tolerancia a la glucosa oral (p / 0,05) y de insulinemia a los 30, 60 y 120 (p / 0,0001), lo que fue mayor en el grupo III. Se diagnosticó intolerancia en ayunas en una mujer de cada grupo y tolerancia alterada en una del II y III. No hubo diferencias significativas entre grupos para los índices de sensibilidad o resistencia a la insulina en ayunas; ni del HOMA entre mujeres normopeso vs. sobrepeso-obesidad (p / 0,05). La mediana de los índices de la prueba de tolerancia a la glucosa oral fue menor para los de sensibilidad (Belfiore2, Ribel) y mayor para los de resistencia a la insulina (Ins2glu2, ATI, IITotal) en el Grupo III. El DATI/DATG, Matsuda y BetaHOMA no tuvieron diferencias significativas. Conclusiones: Las mujeres con síndrome de ovario poliquístico tienen mayor respuesta glucémica, resistencia a la insulina e hiperinsulinismo postsobrecarga de glucosa que las mujeres con función ovárica normal, más manifiesta en el fenotipo clásico. Los índices de ayuno son menos sensibles, independientemente del peso corporal. Tienen mayor utilidad: insulinemia a los 60 minutos de la prueba de tolerancia a la glucosa oral, Belfiore2, ATI e IITotal(AU)

ABSTRACT Introduction: Insulin resistance is common in polycystic ovary syndrome, with differences between phenotypes and discrepancies on how to measure it. Objective: To identify disorders of insulin sensitivity and resistance in women with polycystic ovarian syndrome and determine if the latter is greater in the classic phenotype. Methods: The study included 152 women. 45 of them had no polycystic ovary syndrome (Group I), 46 had clinical polycystic ovary syndrome (Group II) and 61 had classic polycystic ovary syndrome (Group III). Oral glucose tolerance test was performed, fasting insulin sensitivity or resistance indices (HOMA-IR, I0 / G0, FIRI, ISI, Belfiore, Bennet, Quicki, Raynaud) were calculated and the tolerance test to oral glucose (Belfiore2, Ribel, Ins2glu2, ATI, IITotal, DATI / DATG, Matsuda, BetaHOMA) was also assessed. Kruskal-Wallis, Mann-Whitney and Chi square tests were used. Results: Women with polycystic ovarian syndrome had more global and central obesity (p /0.05), more blood glucose level at 30, 120 and 180 minutes of the oral glucose tolerance test (p /0.05 ) and insulinemia at 30, 60 and 120 (p /0.0001), which was higher in group III. Fasting intolerance was diagnosed in one woman in each group and altered tolerance in one of group II and group III, respectively. There were no significant differences between groups for fasting insulin sensitivity or resistance indices, nor for HOMA among normal weight women vs. overweight-obesity (p / 0.05). The median indexes of the oral glucose tolerance test were lower for those of sensitivity (Belfiore2, Ribel) and higher for those of insulin resistance (Ins2glu2, ATI, IITotal) in Group III. The DATI / DATG, Matsuda and BetaHOMA had no significant differences. Conclusions: Women with polycystic ovarian syndrome have higher glycemic response, insulin resistance and post-overload glucose hyperinsulinism than women with normal ovarian function, which is more evident in the classical phenotype. Fasting rates are less sensitive, regardless of body weight. Tests such as insulinemia 60 minutes after the oral glucose tolerance, Belfiore 2, ATI and IITotal are most useful(AU)