Associação entre a doença pancreática gordurosa não alcoólica e o índice triglicérides/glicose / Association between nonalcoholic fatty pancreatic disease and triglyceride/glucose index

ABSTRACT Background: Nonalcoholic fatty pancreatic disease (NAFPD) is an increase of fat in the pancreas, and has an important association with insulin resistance (IR) and type 2 diabetes mellitus. Research has confirmed that the triglyceridemia/glycemia (TyG) index determines IR as much as does the hyperinsulinemic-euglycemic clamp assessment as the homeostasis model testing of IR (HOMA-IR). Objective: To eva­luate the association between degree of NAFPD and TyG index. Methods: In 72 patients undergoing ultrasound of abdomen with a diagnosis of NAFPD, insulin, glucose, and triglycerides levels were evaluated. The HOMA-IR and TyG indexes were used as a reference for IR. The degrees of NAFPD and the TyG index were presented through the receiver operating characteristics (ROC) curves in order to evaluate the association between different degrees of NAFPD, and the correlation of NAFPD with HOMA-IR was also evaluated. Results: There was a statistically significant correlation between the degree of NAFPD and the TyG index. The AUROC curve for the TyG index for predicting the degree of NADPD was 0.855 (0.840-0.865). The intensity-adjusted probabilities of the degree of NAFPD were more strongly associated with TyG values when compared with HOMA-IR. Conclusion: In this study the TyG index correlated positively with the degree of NAFPD, performing better than HOMA-IR.

RESUMO Contexto: A doença pancreática gordurosa não alcoólica (DPGNA) é um aumento de gordura pancreática, e tem uma importante associação com a resistência à insulina (RI) e com diabetes mellitus tipo 2. Pesquisas confirmaram que o índice triglicérides/glicemia (TyG) determina a RI tanto quanto a avaliação da clamp hiperinsulinêmico-euglicêmico como o teste do modelo de homeostasia da RI (HOMA-IR). Objetivo: Avaliar a associação entre o grau de DPGNA e o índice TyG. Métodos: Em 72 pacientes submetidos a ultrassonografia do abdome com diagnóstico de DPGNA, foram avaliados os níveis de insulina, glicose e triglicérides. Os índices HOMA-IR e TyG foram usados como referência para RI. Os graus de DGPNA e o índice TyG foram apresentados através da curva ROC com o objetivo de avaliar a associação entre diferentes graus de DPGNA, e a correlação do DGPNA com o HOMA-IR também foi avaliada. Resultados: Houve uma correlação estatisticamente significativa entre o grau de DPGNA e o índice TyG. A curva AUROC para o índice TyG para prever o grau do NADPD foi 0,855 (0,840-0,865). As probabilidades ajustadas de intensidade do grau de NAFPD foram mais fortemente associadas aos valores de TyG quando comparadas com o HOMA-IR. Conclusão: Neste estudo, o índice TyG correlacionou-se positivamente com o grau de DPGNA, tendo um desempenho melhor que o índice HOMA-IR.

El Estimador de Sensibilidad Insulínica de Punto Único (SPISE) supera a marcadores antropométricos de uso rutinario en la pesquisa de riesgo cardiometabólico asociado a obesidad: un estudio en adolescentes de la Región Metropolitana / The single Point Insulin Sensitivity Estimator (SPISE) outperforms routine anthropometric markers in the screening of obesity-related cardiometabolic risk: a study in adolescents from the Metropolitan Region

El Estimador de Sensibilidad a la Insulina de Punto Único (SPISE) es un biomarcador de sensibilidad a la insulina comparable al Índice de Matsuda. Se estima utilizando el IMC y los niveles de triglicéridos y HDL. El objetivo de este estudio fue comparar el rendimiento diagnóstico de SPISE con el de otros marcadores antropométricos de uso rutinario, como el IMC y la relación cintura | talla, en la pesquisa de insulinoresistencia (IR) y Síndrome Metabólico (MetS) en una muestra de 901 adolescentes de 11 a 16 años. En todos ellos se midió peso, talla, cintura, presión arterial, perfil lipídico, insulina y glicemia. La IR se diagnosticó con el HOMA-IR y el MetS con el criterio de Cook. Un zIMC ≥2.0 DE, un índice cintura/ talla ≥0.54 y un SPISE ≤ 5.4 fueron los puntos de corte utilizados para evaluar el rendimiento de estos marcadores en el diagnóstico de IR y MetS. No hubo diferencias por sexo en la prevalencia de obesidad, IR y MetS. Tanto en hombre como en mujeres, SPISE mostro una mejor capacidad para predecir el MetS (AUC: 0.95 y 0.89, respectivamente) e IR (AUC: 0.83 y 0.79, respectivamente) comparado con el rendimiento diagnóstico de la relación cintura | talla y el IMC-z. De igual manera, el SPISE mostro una mayor sensibilidad para identificar a los portadores de MetS e IR (96% y 75% en varones y 81% y 67% en mujeres, respectivamente). SPISE mostró una mejor capacidad para identificar el riesgo cardiometabólico asociado a la malnutrición por exceso al compararlo con otros indicadores de uso frecuente en clínica. Un índice de SPISE ≤5.4 fue un mejor predictor de MetS e IR que un IMC ≥2.0 DE y una relación cintura | talla ≥0.54.

The Single Point Insulin Sensitivity Estimator (SPISE) is a biomarker of insulin sensitivity comparable to the Matsuda Index. It is estimated using data on BMI, TG, and HDL. We aim to compare the diagnostic performance of SPISE with other routinely used anthropometric markers, such as BMI and waist-to-height ratio, in diagnosing insulin resistance (IR) and Metabolic Syndrome (MetS) in adolescents from 11 to 16 years. Weight, height, waist, blood pressure, lipid profile, insulin, and glycemia were measured. IR was diagnosed with the HOMA-IR and the MetS with the Cook criteria. A BMIz ≥2.0 SD, a waist-to-height ratio ≥0.54, and a SPISE ≤ 5.4 were the cut-off points used for diagnosing IR and MetS. There were no sex differences in the prevalence of obesity, IR, and MetS. In both males and females, SPISE showed a better ability to predict MetS (AUC: 0.95 and 0.89, respectively) and IR (AUC: 0.83 and 0.79, respectively) compared to the waist-to-height ratio and BMI-z. Similarly, SPISE showed greater sensitivity to identify adolescents with MetS and IR (96% and 75% in men and 81% and 67% in women, respectively) than the waist-to-height ratio and BMI-z. SPISE performed better in identifying obesity-related cardiometabolic risk than other frequently used clinical indicators. A SPISE index ≤5.4 was a better predictor of MetS and RI than a BMI ≥2.0 SD and a waist-to-height ratio ≥0.54.

[Cardiovascular risk and insulin resistance in childhood leukemia survivors]. / Riesgo cardiovascular y resistencia insulínica en supervivientes de leucemia infantil.

Introduction: Material and methods: a retrospective study of childhood acute leukemia survivors. Survivors with a diagnosis of leukemia before 16 years of age in a tertiary hospital, during the period of 1998-2018, were selected, who had completed their treatment at least two years earlier. We examined: blood adipokine levels and carbohydrate metabolism, body composition by bioimpedance, and carotid status by ultrasound. Somatometric measures were also taken. Results: the registry showed 82 children diagnosed with acute leukemia, aged between 6 and 16 years. Only 22 met the criteria to be included in the study. Results reveled that 32 % of the sample met the criteria for overweight-obesity, and 36 % had high insulin resistance indexes (IR). Leptin levels were higher in women (15.45 vs. 3.25; p = 0.044) and in obese and overweight subjects, as was the leptin/adiponectin ratio, which rises in the presence of IR (2.52 vs. 0.45; p = 0.037). We observed an increase in carotid intima-media thickness in relation to BMI (0.008; CI, -0.002 to 0.013; p = 0.007) without any association with an increase in fat mass in these patients (0.204; CI, -0.043 to 0.451; p = 0.101). Conclusions: childhood leukemia survivors have a high cardiovascular risk, characterized by an increase in IR, not associated with an increase in fat mass. This risk could justify the implementation of preventive actions in these long-lived patients.

Introducción: Material y métodos: estudio retrospectivo de supervivientes de leucemia aguda en edad infantil. Se seleccionaron aquellos supervivientes con diagnóstico de leucemia antes de los 16 años de edad, en un hospital de tercer nivel y durante el período 1998-2018, que hubieran finalizado su tratamiento como mínimo dos años antes. Se analizaron: niveles de adipokinas y metabolismo hidrocarbonado en sangre, composición corporal mediante bioimpedancia y evaluación ecográfica carotídea. Se tomaron además datos somatométricos. Resultados: de 82 niños con diagnóstico de leucemia aguda, con edades comprendidas entre 6 y 16 años, incluidos en el registro, solamente 22 cumplieron los criterios para ser incluídos en el estudio. Entre los resultados destaca que el 32 % de la muestra cumplían los criterios de sobrepeso-obesidad y el 36 % presentaban índices de resistencia insulínica (RI) elevados. Los niveles de leptina fueron más elevados en las mujeres (15,45 vs. 3,25; p = 0,044) y en los individuos con obesidad o sobrepeso, así como la ratio leptina/adiponectina, que se eleva en presencia de RI (2,52 vs. 0,45; p = 0,037). Se observó un incremento del grosor mediointimal carotídeo en relación con el IMC (0,008; IC: -0,002 a 0,013; p = 0,007) sin asociarse a un aumento de masa grasa en estos pacientes (0,204; IC: -0,043 a 0,451; p = 0,101). Conclusiones: los pacientes supervivientes de leucemia en la edad infantil tienen un riesgo cardiovascular elevado, caracterizado por un aumento de la RI no asociado a aumento de la masa grasa. Este riesgo podría justificar la implementación de medidas preventivas en estos pacientes, cada vez más longevos.

Riesgo cardiovascular y resistencia insulínica en supervivientes de leucemia infantil / Cardiovascular risk and insulin resistance in childhood leukemia survivors

Material y métodos: estudio retrospectivo de supervivientes de leucemia aguda en edad infantil. Se seleccionaron aquellos supervivientes con diagnóstico de leucemia antes de los 16 años de edad, en un hospital de tercer nivel y durante el período 1998-2018, que hubieran finalizado su tratamiento como mínimo dos años antes. Se analizaron: niveles de adipokinas y metabolismo hidrocarbonado en sangre, composición corporal mediante bioimpedancia y evaluación ecográfica carotídea. Se tomaron además datos somatométricos. Resultados: de 82 niños con diagnóstico de leucemia aguda, con edades comprendidas entre 6 y 16 años, incluidos en el registro, solamente 22 cumplieron los criterios para ser incluídos en el estudio. Entre los resultados destaca que el 32 % de la muestra cumplían los criterios de sobrepeso-obesidad y el 36 % presentaban índices de resistencia insulínica (RI) elevados. Los niveles de leptina fueron más elevados en las mujeres (15,45 vs. 3,25; p = 0,044) y en los individuos con obesidad o sobrepeso, así como la ratio leptina/adiponectina, que se eleva en presencia de RI (2,52 vs. 0,45; p = 0,037). Se observó un incremento del grosor mediointimal carotídeo en relación con el IMC (0,008; IC: -0,002 a 0,013; p = 0,007) sin asociarse a un aumento de masa grasa en estos pacientes (0,204; IC: -0,043 a 0,451; p = 0,101). Conclusiones: los pacientes supervivientes de leucemia en la edad infantil tienen un riesgo cardiovascular elevado, caracterizado por un aumento de la RI no asociado a aumento de la masa grasa. Este riesgo podría justificar la implementación de medidas preventivas en estos pacientes, cada vez más longevos. (AU)

Material and methods: a retrospective study of childhood acute leukemia survivors. Survivors with a diagnosis of leukemia before 16 years of age in a tertiary hospital, during the period of 1998-2018, were selected, who had completed their treatment at least two years earlier. We examined: blood adipokine levels and carbohydrate metabolism, body composition by bioimpedance, and carotid status by ultrasound. Somatometric measures were also taken. Results: the registry showed 82 children diagnosed with acute leukemia, aged between 6 and 16 years. Only 22 met the criteria to be included in the study. Results reveled that 32 % of the sample met the criteria for overweight-obesity, and 36 % had high insulin resistance indexes (IR). Leptin levels were higher in women (15.45 vs. 3.25; p = 0.044) and in obese and overweight subjects, as was the leptin/adiponectin ratio, which rises in the presence of IR (2.52 vs. 0.45; p = 0.037). We observed an increase in carotid intima-media thickness in relation to BMI (0.008; CI, -0.002 to 0.013; p = 0.007) without any association with an increase in fat mass in these patients (0.204; CI, -0.043 to 0.451; p = 0.101). Conclusions: childhood leukemia survivors have a high cardiovascular risk, characterized by an increase in IR, not associated with an increase in fat mass. This risk could justify the implementation of preventive actions in these long-lived patients. (AU)

Perfil lipoproteico avanzado en individuos con metabolismo glucémico normal y alterado / Advanced lipoprotein profile in individuals with normal and impaired glucose metabolism

Introducción y objetivos: Varios tipos de lipoproteínas, aparte de las lipoproteínas de baja densidad (LDL), tienen relación causal con la enfermedad cardiovascular. Se analizó el perfil lipoproteico avanzado de individuos con metabolismo glucémico normal y alterado provenientes de una región mediterránea.Métodos: Estudio transversal en 929 participantes (463 normoglucémicos, 250 prediabéticos y 216 con diabetes tipo 2) sin insuficiencia renal, enfermedad cardiovascular ni tratamiento hipolipemiante. Se analizaron los perfiles lipoproteicos convencional y avanzado (resonancia magnética [RM] espectroscópica).Resultados: En comparación con los varones, las mujeres normoglucémicas mostraron menores concentraciones de triglicéridos y cLDL, menos partículas (P) de LDL y todas sus subclases y menos contenido en colesterol y triglicéridos, mayor concentración de P de lipoproteínas de alta densidad (HDL) y de todas sus variables relacionadas (p ≤ 0,05 para todas las comparaciones). En comparación con los normoglucémicos, los diabéticos mostraron una mayor concentración de P-VLDL grandes y pequeñas (p <0,05), además de una menor concentración de P-HDL totales y medianas (p <0,05). Se halló relación directa del perímetro de la cintura y el fatty liver index con un perfil proaterogénico.Conclusiones: Las mujeres mostraron un mejor perfil lipoproteico avanzado que los varones. Se halló relación directa de los índices de adiposidad relacionados con resistencia insulínica con un perfil lipídico proaterogénico. La RM mostró alteraciones en partículas lipoproteicas distintas de las LDL en los diabéticos, a menudo asociadas con mayor riesgo cardiovascular. Nuestros hallazgos confirman la utilidad del análisis lipoproteico avanzado mediante RM espectroscópica para descubrir nuevas dianas terapéuticas con que prevenir eventos cardiovasculares en los individuos en riesgo (AU)

Introduction and objectives: Several types of lipoproteins beyond low-density lipoproteins (LDL) are causally related to cardiovascular disease. We aimed to analyze an advanced lipoprotein profile in individuals with normal and impaired glucose metabolism from different cohorts of a Mediterranean region.Methods: Cross-sectional study in 929 participants (463 normoglycemia, 250 prediabetes, and 216 type 2 diabetes mellitus) with normal renal function, free from cardiovascular disease, and without lipid-lowering treatment. Conventional and advanced (nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analyzed.Results: Compared with men, normoglycemic women showed lower serum triglyceride and LDL cholesterol concentrations, lower total LDL particles (P) as well as their subclasses and their cholesterol and triglyceride content, higher high-density lipoproteins (HDL)-P and all HDL-related variables (P≤ .05 for all comparisons). Compared with normoglycemic participants, diabetic participants showed higher large and small very LDL-P concentrations (P <.05) and lower total HDL-P and medium HDL-P concentrations (P <.05). Waist circumference and Fatty Liver Index were positively associated with a proatherogenic profile.Conclusions: Women had a better advanced lipoprotein profile than did men. Adiposity indexes related to insulin-resistance were positively associated with a proatherogenic lipid profile. NMR revealed altered lipoprotein particles other than LDL in participants with diabetes, frequently associated with an increased cardiovascular risk. Our findings support the usefulness of extended lipoprotein analysis by NMR spectroscopy to uncover new therapeutic targets to prevent cardiovascular events in at-risk participants (AU)

Advanced lipoprotein profile in individuals with normal and impaired glucose metabolism.

INTRODUCTION AND OBJECTIVES: Several types of lipoproteins beyond low-density lipoproteins (LDL) are causally related to cardiovascular disease. We aimed to analyze an advanced lipoprotein profile in individuals with normal and impaired glucose metabolism from different cohorts of a Mediterranean region. METHODS: Cross-sectional study in 929 participants (463 normoglycemia, 250 prediabetes, and 216 type 2 diabetes mellitus) with normal renal function, free from cardiovascular disease, and without lipid-lowering treatment. Conventional and advanced (nuclear magnetic resonance [NMR] spectroscopy) lipoprotein profiles were analyzed. RESULTS: Compared with men, normoglycemic women showed lower serum triglyceride and LDL cholesterol concentrations, lower total LDL particles (P) as well as their subclasses and their cholesterol and triglyceride content, higher high-density lipoproteins (HDL)-P and all HDL-related variables (P≤ .05 for all comparisons). Compared with normoglycemic participants, diabetic participants showed higher large and small very LDL-P concentrations (P <.05) and lower total HDL-P and medium HDL-P concentrations (P <.05). Waist circumference and Fatty Liver Index were positively associated with a proatherogenic profile. CONCLUSIONS: Women had a better advanced lipoprotein profile than did men. Adiposity indexes related to insulin-resistance were positively associated with a proatherogenic lipid profile. NMR revealed altered lipoprotein particles other than LDL in participants with diabetes, frequently associated with an increased cardiovascular risk. Our findings support the usefulness of extended lipoprotein analysis by NMR spectroscopy to uncover new therapeutic targets to prevent cardiovascular events in at-risk participants.

Tres versiones del "Ogtt Squeezer", un programa para evaluar de un vistazo la información metabólica de la curva de tolerancia a la glucosa / Three versions of the "Ogtt Squeezer", a program to evaluate ataglance the metabolic information of the oral glucose tolerance test

El diagnóstico clínico de resistencia insulínica (RI) es difícil, ya que el Clamp no es aplicable a la clínica. El así llamado "síndrome metabólico", un predictor clínico de la RI, no identifica alrededor de la mitad de los sujetos afectados. Previamente, definimos adecuadamente (Análisis ROC) los niveles de corte diagnóstico de los siguientes predictores bioquímicos: HOMA1, HOMA2, QUICKI e ISI-Composite, a través de analizar datos de 90 sujetos (53 no resistentes y 37 resistentes) que tenían una medición directa de su resistencia insulínica (Test de supresión pancreática, TSP, Test de Reaven) y también, una curva de tolerancia a la glucosa oral (CTG). Los puntos de corte obtenidos exhibieron un mucho mejor desempeño diagnóstico comparados con los puntos de corte convencionales. También encontramos un predictor nuevo, simple, económico y eficiente, el I0*G60. Definimos la "normalidad metabólica" de la CTG usando las medianas de los valores de varios parámetros en 312 sujetos con un G120 dentro de los 2 primeros terciles del grupo de normo-tolerantes a la glucosa (NGT, n=468; G120: 51-110 mg/dL, los con mejor función beta insular). A las medianas de la función beta insular y de la sensibilidad insulínica se les asignó un valor de un 100%. Se calculó el % relativo de función beta insular (%RFBI) y el % relativo de sensibilidad insulínica (%RSI) del resto de la cohorte (n=573) contra estos valores de referencia. El "OGTT Squeezer" se escribió en Excel. Las glicemias y las insulinemias de la CTG fueron las entradas del programa. Las salidas fueron: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictores) y el índice insulinogénico, el índice de disposición, %RFBI y %RSI (parámetros). El programa también caracterizó la tolerancia glucídica de acuerdo a los criterios de la ADA 2003. El formato final del programa, HTML 5, facilita su uso. Desarrollamos tres versiones del programa: completa, abreviada y mínima.

Clinically, diagnosing insulin resistance (IR) is difficult since the Clamp is not applicable to clinical work. The so-called "Metabolic Syndrome", a clinical surrogate of IR, fails to identify around 50% of affected subjects. Previously, we properly defined (ROC Analysis) the diagnostic cut-offs of the following biochemical predictors: HOMA1, HOMA2, QUICKI, and ISI-Composite by analyzing data from 90 subjects (53 non-insulin-resistant and 37 insulin-resistant subjects) who had a direct measurement of insulin resistance (Pancreatic Suppression Test, PST, Reaven's Test), and also, an Oral Glucose Tolerance Test (OGTT). The resulting cut-offs exhibited much better performances compared with the conventional cut-offs. We also found a new, simple, inexpensive and efficient predictor, the I0*G60. We chose to define the "metabolic normalcy" of the OGTT by using the median values of several parameters in 312 NGT subjects with a G120 in the first 2 tertiles of the NGT group (n=468; G120: 51-110 mg/dL, those with the best beta-cell function). The median values of both Beta-Cell Function and Insulin Sensitivity of these subjects were assigned a 100% value. Both % Relative Beta-Cell Function (%RBCF) and % Relative Insulin Sensitivity (%RIS) of everyone else in the cohort (n=573) was calculated against these reference values. The "OGTT Squeezer" was written in Excel. The OGTT's glucose and insulin values served as the inputs of the program. The outputs were: I0*G60, ISI-OL, QUICKI, and HOMA1 (predictors), and Insulinogenic Index, Disposition Index, %RBCF, and %RIS (parameters). Moreover, the program characterized the OGTT according to the ADA 2003 criteria. The HTML 5 format of the program facilitates its use. We developed 3 versions of the program: complete, abbreviated, and minimal versions.

Relationship between serum concentrations of uric acid, insulin resistance and metabolic alterations in adolescents / Relação entre concentrações séricas de ácido úrico, resistência insulínica e alterações metabólicas em adolescentes

ABSTRACT Objective: To verify the possible relationship between serum uric acid concentrations and insulin resistance in adolescents. Methods: This is a cross-sectional study with 74 participants from a public school in São Luís, Maranhão, aged between 10 and 19 years. The study was approved by the Ethics and Research Committee of the University Hospital of the Universidade Federal do Maranhão (UFMA) under report 2,673,791. Anthropometric measurements, blood pressure and blood collection were performed. The participants were divided into two groups: group 1 (with hyperuricemia) and group 2 (without hyperuricemia). Data analysis was performed by means of the Stata program. Results: Anthropometric measurements, such as body mass index and waist circumference, had statistical significance (p < 0.05) among groups with hyperuricemia and without hyperuricemia, as well as the percentage of body fat (p = 0.0423) and systolic and diastolic blood pressure (p = 0.0235). Biochemical parameters for total cholesterol (p = 0.0172), triglycerides (p = 0.0268), glucose (p = 0.0284) and TyG index (p = 0.0416) had statistical significance in the hyperuricemia group when compared to the group without hyperuricemia. Conclusion: According to the obtained results, the participants with insulin resistance calculated by the TyG index presented high serum acid levels, demonstrating a statistically significant correlation.

RESUMEN Objetivo: Verificar la posible relación entre concentraciones séricas de ácido úrico y resistencia a la insulina en adolescentes. Métodos: Estudio transversal con 74 participantes de una escuela pública en São Luís, Maranhão, con edades entre 10 y 19 años. El estudio es aprobado por el Comité de Ética e Investigación del Hospital Universitario de la Universidad Federal de Maranhão (UFMA) bajo dictamen 2.673.791. Se realizaron mediciones antropométricas, de presión arterial y extracción de sangre. Los participantes se dividieron en dos grupos: grupo 1 (con hiperuricemia) y grupo 2 (sin hiperuricemia). El análisis de datos se realizó utilizando el programa Stata. Resultados: Las medidas antropométricas, como el índice de masa corporal (IMC) y la circunferencia de la cintura, tuvieron significancia estadística (p < 0,05) entre los dos grupos, así como el porcentaje de grasa corporal (p = 0,0423) y la presión arterial sistólica y diastólica (p = 0,0235). Los parámetros bioquímicos referentes a colesterol total (p = 0,0172), triglicéridos (p = 0,0268), glucosa (p = 0,0284) e índice TyG (p = 0,0416) fueron estadísticamente significativos en el grupo con hiperuricemia, en comparación con el grupo sin hiperuricemia. Conclusión: De acuerdo a los resultados obtenidos, los participantes con resistencia a la insulina, en base al cálculo mediante el índice TyG, presentaron niveles séricos elevados de ácido úrico, mostrando una correlación estadísticamente significativa.

RESUMO Objetivo: Verificar a possível relação entre concentrações séricas de ácido úrico e resistência insulínica em adolescentes. Métodos: Estudo de caráter transversal com 74 participantes oriundos de uma escola pública de São Luís, Maranhão, com idades entre 10 e 19 anos. O estudo foi aprovado pelo Comitê de Ética e Pesquisa do Hospital Universitário da Universidade Federal do Maranhão (UFMA) sob o parecer 2.673.791. Medidas antropométricas, pressão arterial e coleta de sangue foram feitas. A divisão dos participantes foi realizada em dois grupos: grupo 1 (com hiperuricemia) e grupo 2 (sem hiperuricemia). A análise de dados foi realizada por meio do programa Stata. Resultados: As medidas antropométricas, como índice de massa corporal (IMC) e circunferência da cintura, tiveram significância estatística (p < 0,05) entre os dois grupos, assim como a porcentagem de gordura corporal (p = 0,0423) e a pressão arterial sistólica e diastólica (p = 0,0235). Os parâmetros bioquímicos referentes a colesterol total (p = 0,0172), triglicerídeos (p = 0,0268), glicose (p = 0,0284) e índice TyG (p = 0,0416) tiveram significância estatística no grupo com hiperuricemia, quando comparados com o grupo sem hiperuricemia. Conclusão: De acordo com os resultados obtidos, os participantes com resistência insulínica, a partir do cálculo pelo índice TyG, apresentaram níveis séricos elevados de ácido úrico, demonstrando correlação estatística significativa.

Repercussões metabólicas e uso dos medicamentos sensibilizadores da insulina em mulheres com síndrome dos ovários policísticos / Metabolic repercussions and use of insulin-sensitizing drugs in women with polycystic ovary syndrome

A síndrome dos ovários policísticos (SOP) é um distúrbio endócrino-metabólico muito frequente no período reprodutivo. Quando associado ao distúrbio metabólico, as mulheres com SOP podem ter ainda risco acrescido para doença cardiovascular. O objetivo deste manuscrito é descrever as repercussões metabólicas, incluindo quais as principais, como investigar e as consequências desse distúrbio sobre a saúde da mulher. É uma revisão narrativa mostrando a implicação da resistência insulínica, das dislipidemias e da síndrome metabólica sobre o sistema reprodutor e sobre o risco cardiovascular da mulher com SOP, bem como do uso de sensibilizadores de insulina no seu tratamento. Conclui-se que a correção dos distúrbios metabólicos na SOP é benéfica tanto para o sistema reprodutor quanto para o cardiovascular. A primeira linha de tratamento é a mudança de estilo de vida e a perda de peso. Na resposta inadequada, o tratamento medicamentoso está recomendado. Nas mulheres com obesidade mórbida que não tiveram bons resultados com o tratamento clínico, a cirurgia bariátrica é uma opção.(AU)

Breastfeeding in children born small for gestational age and future nutritional and metabolic outcomes: a systematic review / Aleitamento materno em crianças nascidas pequenas para idade gestacional e os desfechos nutricionais e metabólicos futuros: revisão sistemática

Abstract Objective: To systematically review evidence related to nutritional and cardiometabolic outcomes in children born at term and small for gestational age and the association with breastfeeding. Source of data: Two independent reviewers searched the MEDLINE, LILACS, SciELO, and Embase databases without time or language restrictions. The PRISMA tool was used, and studies that evaluated infants born at term and small for gestational age, breastfed, and with an evaluation of cardiometabolic outcomes were included. Studies with preterm infants, those that did not have information on breastfeeding, and those with lack of evaluation of the outcome variables were excluded. Also excluded were review articles, editorials, and series of cases. Summary of data: Only seven articles were found that met the abovementioned criteria. There was a great variability in the type of evaluation, as well as in the age of these children. It was demonstrated that breastfeeding promoted growth without body composition alteration and without increased insulin resistance in children with exclusive breastfeeding, when compared to children receiving a higher calorie formula, except for one article that observed an increase in fat mass in exclusively breastfed children. Conclusion: Breastfeeding seems to be a safe feeding practice for infants born at term and small for gestational age, showing no association with deleterious short-term outcomes. Breastfeeding stimulation in these populations seems to be a way of preventing the health problems associated with the high risk of chronic noncommunicable diseases and obesity.

Resumo Objetivo: Revisar sistematicamente as evidências relacionadas aos desfechos nutricionais e cardiometabólicos em crianças nascidas a termo e pequenas para idade gestacional e a relação com o aleitamento materno. Fonte de dados: Dois revisores independentes fizeram buscas nas bases de dados MEDLINE,LILACS, SciELO, EMBASE sem restrições de tempo ou idioma. Foi usada a ferramenta PRISMA sendo incluídos estudos que avaliaram crianças nascidas a termo e pequenas para idade gestacional, amamentadas e com avaliação dos desfechos cardiometabólicos. Foram excluídos estudos com prematuros, aqueles que não trouxessem informação do aleitamento materno, ausência de avaliação das variáveis de desfecho. Também não foram incluídos artigos de revisão, editorial e série de casos. Síntese dos dados: Foram encontrados apenas sete artigos que preencheram os critérios citados acima. Houve uma grande variabilidade na forma de avaliação, assim como na idade dessas crianças. Foi evidenciado que o aleitamento materno promoveu crescimento sem alteração de composição corporal e sem resistência insulínica aumentada nas crianças com aleitamento materno exclusivo, quando comparadas com crianças que receberam fórmula láctea de maior teor calórico, exceto por um artigo que observou aumento de massa gorda nos amamentados exclusivamente. Conclusão: Aleitamento materno parece ser uma forma segura de alimentação para crianças nascidas a termo e pequenas para idade gestacional sem associação com desfechos deletérios em curto prazo. O estímulo ao aleitamento materno nessas populações parece ser um caminho de prevenção aos agravos à saúde associados ao alto risco de doenças crônicas não transmissíveis e à obesidade.

Breastfeeding in children born small for gestational age and future nutritional and metabolic outcomes: a systematic review.

OBJECTIVE: To systematically review evidence related to nutritional and cardiometabolic outcomes in children born at term and small for gestational age and the association with breastfeeding. SOURCE OF DATA: Two independent reviewers searched the MEDLINE, LILACS, SciELO, and Embase databases without time or language restrictions. The PRISMA tool was used, and studies that evaluated infants born at term and small for gestational age, breastfed, and with an evaluation of cardiometabolic outcomes were included. Studies with preterm infants, those that did not have information on breastfeeding, and those with lack of evaluation of the outcome variables were excluded. Also excluded were review articles, editorials, and series of cases. SUMMARY OF DATA: Only seven articles were found that met the abovementioned criteria. There was a great variability in the type of evaluation, as well as in the age of these children. It was demonstrated that breastfeeding promoted growth without body composition alteration and without increased insulin resistance in children with exclusive breastfeeding, when compared to children receiving a higher calorie formula, except for one article that observed an increase in fat mass in exclusively breastfed children. CONCLUSION: Breastfeeding seems to be a safe feeding practice for infants born at term and small for gestational age, showing no association with deleterious short-term outcomes. Breastfeeding stimulation in these populations seems to be a way of preventing the health problems associated with the high risk of chronic noncommunicable diseases and obesity.

Lipotoxicidad en músculo esquelético, un camino para investigar / Skeletal muscle lipotoxicity, a way to investigate

Para quienes leen un editorial de la Revista de la Sociedad Argentina de Diabetes saben que la diabetes mellitus tipo 2 (DM2) es una enfermedad compleja, generada a partir de múltiples procesos fisiopatológicos que aún atraen debate. Lo que se encuentra fuera de discusión, a esta altura del conocimiento, es la teoría acerca de que la "grasa ectópica", acumulada en células distintas de los adipocitos, conduce a resistencia a la insulina órgano-específica conocida como lipotoxicidad

Lipotoxicidad en músculo esquelético y su relación con la resistencia insulínica. Estudios en un modelo experimental de Síndrome metabólico / Skeletal muscle lipotoxicity and its relationship with insulin resistance. Studies in an experimental model of metabolic syndrome

Introducción: el acúmulo de lípidos en el músculo esquelético se encuentra estrechamente vinculado con el desarrollo de la resistencia insulínica. Esta última cumple un rol patogénico central en el desarrollo de numerosos desórdenes metabólicos incluidos en el síndrome metabólico. Objetivos: analizar algunas vías metabólicas implicadas en el acúmulo de lípidos en el músculo esquelético y su asociación con la resistencia insulínica en un modelo experimental que mimetiza el fenotipo del síndrome metabólico humano. Materiales y métodos: ratas macho Wistar recibieron una dieta control (DC) o una dieta rica en sacarosa (DRS) durante seis meses. Al final del período experimental se analizó en músculo esquelético gastrocnemio: contenido de triglicéridos (TG), acil-CoA de cadena larga y diacilglicerol, actividad enzimática carnitina palmitoil transferasa muscular (M-CPT1, M-CPT2 y M-CPT total) y masa proteica del PPARα, AMPK y AMPKp. Se determinaron los niveles séricos de TG, AGNE, glucosa, insulina, TNFα y adiponectina. La sensibilidad insulínica se midió por la técnica clamp euglucémica-hiperinsulinémica. Resultados: en los animales alimentados con DRS la dislipemia, hiperglucemia moderada, insensibilidad insulínica e incremento del contenido de especies lipídicas en el músculo esquelético se acompañaron de una disminución en la actividad enzimática M-CPT1 y M-CPT total, y un descenso de la masa proteica del PPARα. Además se observó una reducción de la masa proteica de la AMPKp, la cual se correlacionó con bajos niveles de adiponectina y elevados niveles de TNFα séricos. Conclusiones: los resultados aportan nuevos datos sobre algunos mecanismos involucrados en el desarrollo de la lipotoxicidad en el músculo esquelético en ratas dislipémicas insulinorresistentes

Introduction: the skeletal muscle lipid accumulation is closely linked to the development of insulin resistance. The latter plays a central pathogenic role in the development of numerous metabolic disorders included in the metabolic syndrome. Objectives: to analyze some metabolic pathways involved in the skeletal muscle lipid accumulation and its association with insulin resistance in an experimental model that mimics the phenotype of the human metabolic syndrome. Materials and methods: male Wistar rats received a control diet (CD) or a sucrose rich diet (SRD) for six months. At the end of the experimental period, in gastrocnemius skeletal muscle were analyzed: triglyceride (TG), long chain acyl-CoA and diacylglycerol (DAG) contents, muscle carnitine palmitoyl transferase enzymes activities (M-CPT1, M-CPT2 and total M-CPT) and protein mass levels of PPARα, AMPK and AMPKp. Serum levels of TG, AGNE, glucose and insulin, TNFα and adiponectin were determined. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp technique. Results: in SRD fed animals, dyslipidemia, moderate hyperglycemia, insulin insensitivity and the increased content of lipid species in the skeletal muscle were accompanied by a decrease in the enzymes activities of both M-CPT1 and total M-CPT and protein mass levels of PPARα. In addition, a reduction in the protein mass levels of AMPKp was observed, which was correlated with low serum levels of adiponectin and high levels of TNFα. Conclusions: the results provide new data on some mechanisms involved in the development of lipotoxicity in skeletal muscle in insulin resistant dyslipidemic rats

Lactancia materna, obesidad y síndrome metabólico en la edad escolar / Breastfeeding, obesity and metabolic syndrome at school age

INTRODUCCIÓN: La lactancia materna (LM) puede ser un factor protector de la obesidad y sus complicaciones metabólicas. OBJETIVO: Determinar la asociación entre el antecedente de amamantamiento y la presencia de obesidad, síndrome metabólico (SM) y resistencia insulínica (RI). PACIENTES Y MÉTODOS: Estudio transversal en 20 escuelas públicas de Santiago, Chile. Se evaluó antropometría, presión arterial, perfil lipídico, glicemia, insulinemia e índice HOMA. Los padres respondieron una encuesta sobre el antecedente de LM. Se definió SM según criterios de Cook y RI como HOMA > percentil 90. RESULTADOS: Se recibieron 3.278 encuestas válidas. La edad promedio fue de 11,4 ± 1 años, siendo 52,3% mujeres. La mayoría (98,2%) recibió LM, con una prevalencia de 15,9% de obesidad versus 18,6% en los que no la recibieron (p = 0,039). Hubo una tendencia no significativa a que SM y sus componentes, excepto RI, fueran más prevalentes en el grupo no amamantado. Los escolares que recibieron LM por 3-6 meses presentaron una menor prevalencia de obesidad y de algunos componentes de SM que los que recibieron menor tiempo o no la recibieron; el efecto fue inverso cuando la LM se prolongó por más de 9 meses. CONCLUSIONES: La prevalencia de obesidad fue mayor en los escolares que no fueron amamantados. Durante el primer semestre, la LM de mayor duración se asoció a menor prevalencia de obesidad y complicaciones metabólicas.

INTRODUCTION: Breastfeeding (BF) can be a protective factor against obesity and its associated metabolic complications. OBJECTIVE: To determine the association between breastfeeding history and present obesity, metabolic syndrome (MS) and insulin resistance (IR). PATIENTS AND METHODS: Cross-sectio nal study in 20 public schools in Santiago, Chile. Anthropometry and blood pressure were assessed. Blood lipids, glucose, insulin and HOMA index were measured in a fast blood sample. Parents answe red a survey on BF. MS was defined according to Cook's criteria and IR as HOMA > 90th percentile. Parents answered a survey about the antecedent of breastfeeding. Chi2 and Fischer tests were used (SSPS). RESULTS: 3,278 surveys were valid. Average age: 11.4 ± 1 years, 52.3% were female. Most of them (98.2%) were breasted, with a 15.9% prevalence of obesity versus 18.6% in the group that was not breastfed (p = 0.039). There was a non-significant trend of higher prevalence in MS and its components (except IR) in the non-breastfed group. The group breastfed from three to six months had a lower prevalence of obesity and MS components than the 0 to 3 months group ; the effect was the opposite when BF lsted longer than nine months. CONCLUSIONS: The prevalence of obesity was higher in children that did not received breastfeeding. A longer breastfeeding time during the first semester of life was associated with lower prevalence of obesity and metabolic complications.

Thyroid-stimulating Hormone and Insulin Resistance: Their Association with Polycystic Ovary Syndrome without Overt Hypothyroidism / Hormônio tireoestimulante e resistência insulínica: sua associação com a síndrome do ovário policístico sem hipotireoidismo clínico

Abstract Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR)≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR. Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 - 10 mIU/L. Conclusion In women with PCOS without overt hypothyroidism, TSH ≥2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.

Resumo Objetivo Este estudo analisou a efetividade do hormônio tireoestimulante (TSH) como preditor da resistência insulínica (IR), bem como a associação do TSH com os parâmetros clínicos e metabólicos de mulheres com síndrome do ovário policístico (PCOS) sem hipotireoidismo clínico. Desenho do Estudo Estudo de corte transversal com inclusão de mulheres com PCOS e sem hipotireoidismo clínico (n =168). Métodos Utilizou-se análise através de curva ROC (Receiver operating characteristic) para determinar o valor de corte para o nível sérico de TSH que poderia maximizar a sensibilidade e especificidade para o diagnóstico de IR considerada com avaliação da homeostase de resistência insulínica (HOMA-IR) ≥ 2.71. Parâmetros clínicos e metabólicos foram comparados de acordo com o ponto de corte de TSH determinado e com a presença de IR. Resultados Níveis séricos de TSH ≥2.77 mIU/L estiveram associados com o diagnóstico de IR, com sensibilidade de 47.9% e especificidade de 65.3%. Não foram evidenciadas diferenças nos parâmetros clínicos, hormonais e metabólicos quando TSH < 2.77 ou TSH de 2.77 - 10 mIU/L. Conclusão Em mulheres com PCOS sem hipotireoidismo, TSH ≥2.77 mIU/L está associado a IR, porém com baixa sensibilidade, mostrando que a dosagem de TSH não é um bom preditor de IR nesta população. Também não se evidenciou alteração clínica ou metabólica que justificasse alteração na investigação desta população. Assim, a resistência insulínica deve ser investigada em todas as mulheres com PCOS, independente dos níveis séricos de TSH.

Insulin binding characteristics in canine muscle tissue: effects of the estrous cycle phases / Características de ligação da insulina no tecido muscular canino: efeitos da fase do ciclo estral

Hormonal fluctuations during the different estrous cycle are a well-recognized cause of insulin resistance in bitches, and little is known about insulin receptor binding or post-binding defects associated with insulin resistance in dogs. To evaluate insulin binding characteristics in muscle tissue of bitches during the estrous cycle, 17 owned bitches were used in the study (six in anestrus, five in estrus, and six in diestrus). An intravenous glucose tolerance test (IVGTT) was performed in all patients by means of injection of 1mL/kg of a glucose 50% solution (500mg/kg), with blood sample collection for glucose determination at 0, 3, 5, 7, 15, 30, 45 and 60 minutes after glucose infusion. Muscle samples, taken after spaying surgery, were immediately frozen in liquid nitrogen and then stored at -80 ºC until the membranes were prepared by sequential centrifugation after being homogenized. For binding studies, membranes were incubated in the presence of 20,000cpm of human 125I-insulin and in increasing concentrations of unlabeled human regular insulin for cold saturation. The IVGTT showed no differences among bitches during the estrous cycle regarding baseline glycemia or glycemic response after glucose infusion. Two insulin binding sites - high-affinity and low-affinity ones - were detected by Scatchard analysis, and significant statistical differences were observed in the dissociation constant (Kd1) and maximum binding capacity (Bmax1) of the high-affinity binding sites. The Kd1 for the anestrus group (6.54±2.77nM/mg of protein) was smaller (P<0.001) than for the estrus (28.54±6.94nM/mg of protein) and diestrus (15.56±3.88nM/mg of protein) groups. Bmax1 in the estrus (0.83±0.42nM/mg of protein) and diestrus (1.24±0.24nM/mg of protein) groups were also higher (P<0.001) than the values observed in anestrus (0.35±0.06nM/mg of protein). These results indicate modulation of insulin binding characteristics during different phases of the estrous cycle in dogs, showing that muscle insulin binding affinity for its receptor is reduced during estrus and diestrus. However, this poor hormone-receptor affinity is compensated for by a greater total binding capacity, once there is no difference in patients' glycemic response after an intravenous glucose load.(AU)

As flutuações hormonais durante as diferentes fases do ciclo estral são uma causa importante de resistência insulínica em fêmeas caninas, e poucas informações são conhecidas sobre defeitos na ligação da insulina ao seu receptor, ou defeitos pós-receptor associados com resistência à insulina em cães. Para avaliar as características da ligação insulina-receptor no tecido muscular de cadelas durante o ciclo estral, dezessete pacientes foram utilizadas no estudo (seis em anestro, cinco em estro e seis em diestro). Um teste de tolerância à glicose intravenosa (IVGTT) foi realizado em todas as pacientes por meio da infusão de 1mL/kg de uma solução de glicose 50% (500mg/kg), com coletas de sangue para determinação de glicemia nos tempos 0, 3, 5, 7, 15, 30, 45 e 60 minutos da injeção de glicose. Amostras de tecido muscular foram coletadas durante ovariohisterectomia, imediatamente congeladas em nitrogênio líquido, e posteriormente armazenadas a -80°C até a preparação das membranas por meio de homogeneização e centrifugação sequencial. Para os experimentos de ligação hormônio-receptor, as membranas foram incubadas na presença de 20.000cpm de 125I-insulina humana, e concentrações crescentes de insulina regular humana não marcada para saturação fria. O IVGTT não mostrou diferenças entre as pacientes em diferentes fases do ciclo estral com relação a glicemia basal, ou na resposta glicêmica após infusão de glicose nos tempos estudados. Dois sítios de ligação da insulina, um de alta-afinidade, e outro de baixa afinidade, foram detectados pela análise de Scatchard, e diferenças significativas foram detectadas na constante de dissociação (Kd1) e capacidade de ligação máxima (Bmax1) dos sítios de ligação de alta-afinidade. O Kd1 para o grupo anestro (6,54±2,77nM/mg de proteína) foi menor (P<0,001) que os Kd1 dos grupos estro (28,54±6,94 nM/mg de proteína) e diestro (15,56±3,88nM/mg de proteína). Os Bmax1 dos grupos estro (0,83±0,42nM/mg de proteína) e diestro (1,24±0,24nM/mg de proteína) também foram maiores que os valores encontrados no grupo anestro (0,35±0,06nM/mg de proteína). Estes resultados demonstram uma modulação das características de ligação da insulina nas diferentes fases do ciclo estral em cães, evidenciando uma menor afinidade de ligação da insulina ao seu receptor no tecido muscular durante o estro e diestro. Contudo, esta menor afinidade de ligação hormônio-receptor é compensada por uma maior capacidade de ligação, o que fica também evidenciado pela ausência de diferenças na resposta glicêmica das pacientes após um desafio com glicose por via endovenosa.(AU)

Association between triglyceride/HDL cholesterol ratio and carotid atherosclerosis in postmenopausal middle-aged women. / Asociación entre la razón triglicéridos/colesterol HDL y ateromatosis carotídea en mujeres posmenopáusicas de mediana edad.

BACKGROUND AND OBJECTIVE: The triglyceride/HDL cholesterol ratio, as a surrogate marker of insulin resistance, may be associated to presence of subclinical carotid atherosclerosis in postmenopausal women. The aim of this study was to explore this association. PATIENTS AND METHODS: Women (last menstrual period≥2 years) in primary prevention up to 65 years of age were recruited. Association between the triglyceride/HDL cholesterol (HDL-C) ratio and presence of carotid plaque, assessed by ultrasonography, was analyzed. ROC analysis was performed, determining the precision of this ratio to detect carotid plaque. RESULTS: A total of 332 women (age 57±5 years) were recruited. Triglyceride/HDL-C ratio was 2.35±1.6. Prevalence of carotid plaque was 29%. Women with carotid plaque had higher triglyceride/HDL-C ratios (3.33±1.96 vs. 2.1±1.2, P<.001) than women with no carotid plaque. A positive relationship was seen between quintiles of this ratio and prevalence of carotid plaque (p<.001). Regardless of other risk factors, women with higher triglyceride/HDL-C ratios were more likely to have carotid plaque (odds ratio 1.47, 95% confidence interval 1.20-1.79, P<.001). The area under the curve of the triglyceride/HDL-C ratio to detect carotid plaque was .71 (95% confidence interval .65 to .76), and the optimal cut-off point was 2.04. CONCLUSIONS: In postmenopausal women in primary prevention, insulin resistance, estimated from the triglyceride/HDL-C ratio, was independently associated to a greater probability of carotid plaque. A value of such ratio greater than 2 may be used for assessing cardiovascular risk in this particular group of women.

Metabolic syndrome, insulin resistance and other cardiovascular risk factors in university students / Síndrome metabólica, resistência insulínica e outros fatores de risco cardiovascular em universitários

Abstract A cross-sectional population-based study using questionnaire and anthropometric data was conducted on 968 university students of São Luís, Brazil, from which 590 showed up for blood collection. In the statistical analysis the Student t-test, Mann-Whitney and chi-square tests were used. The prevalence of metabolic syndrome by the Joint Interim Statement (JIS) criteria was 20.5%, almost three times more prevalent in men (32.2%) than in women (13.5%) (P < 0.001). The prevalence of insulin resistance was 7.3% and the prevalence of low HDL-cholesterol was high (61.2%), both with no statistically significant differences by sex. Men showed a higher percentage of smoking, overweight, high blood pressure, high blood glucose and increased fasting hypertriglyceridemia. Women were more sedentary. University students of private institutions had higher prevalences of sedentary lifestyle, obesity, abdominal obesity, elevated triglycerides and metabolic syndrome than students from public institutions. High prevalences of metabolic syndrome, insulin resistance and other cardiovascular risk factors were found in this young population. This suggests that the burden of these diseases in the future will be increased.

Resumo Estudo transversal de base populacional, usando questionários e medidas antropométricas, feito em 968 universitários de São Luís, dos quais 590 realizaram também coleta de sangue. Na análise estatística foram utilizados os testes t de Student, Mann-Whitney e qui-quadrado. A prevalência de síndrome metabólica pelo critério Joint Interim Statement (JIS) foi de 20,5%, sendo quase três vezes mais prevalente nos homens (32,2%) do que nas mulheres (13,5%) (P < 0,001). A prevalência de resistência insulínica foi de 7,3% e a de HDL-colesterol diminuído foi elevada (61,2%), ambas sem diferença estatisticamente significante por sexo. Os homens apresentaram maior percentual de tabagismo, sobrepeso, hipertensão arterial, glicemia em jejum aumentada e hipertrigliceridemia. As mulheres eram mais sedentárias. Os universitários de instituições privadas tiveram maiores prevalências de sedentarismo, obesidade, obesidade abdominal, triglicerídeos aumentados e síndrome metabólica do que os alunos de instituições públicas. Prevalências elevadas de síndrome metabólica, resistência insulínica e outros fatores de risco cardiovascular foram encontradas nesta população jovem. Isto sugere que a carga destas doenças será elevada no futuro.

Mechanisms linking brain insulin resistance to Alzheimer's disease / Mecanismos que ligam a resistência insulínica cerebral à doença de Alzheimer: uma breve revisão

ABSTRACT. Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, accumulation of AGEs, ROS and RNS with increased production of neuro-inflammation and activation of pro-apoptosis cascade. Impairment in insulin receptor function and increased expression and activation of insulin-degrading enzyme (IDE) have also been described. These processes compromise neuronal and glial function, with a reduction in neurotransmitter homeostasis. Insulin/IGF resistance causes the accumulation of AßPP-Aß oligomeric fibrils or insoluble larger aggregated fibrils in the form of plaques that are neurotoxic. Additionally, there is production and accumulation of hyper-phosphorylated insoluble fibrillar tau which can exacerbate cytoskeletal collapse and synaptic disconnection.

RESUMO. Atualmente, muitos estudos têm indicado que o Diabetes Mellitus (DM) pode aumentar o risco de desenvolver doença de Alzheimer (DA). Esta revisão tem o objetivo de descrever brevemente os conceitos atuais sobre os mecanismos que associam DM, resistência/deficiência de insulina à DA. Resistência à insulina/fator de crescimento similar à insulina (IGF) pode contribuir para a neurodegeneração através de vários mecanismos os quais envolvem: déficit metabólico e energético, prejuízo na função do transportador de glicose-4, estresse oxidativo e do retículo endoplasmático, disfunção mitocondrial, acúmulo de AGEs, ROS e RNS com aumento na produção da neuro-inflamação e ativação da cascata pró-apoptóptica. Prejuízo na função do receptor de insulina, aumento na expressão e ativação da enzima de degradação da insulina (EDI) também têm sido descritos. Esses processos comprometem a função neuronal e glial, com redução da homeostase de neurotransmissor. Resistência à insulina/IGF causa acúmulo de fibrilas de oligômeros de PPßA-ßA e grandes agregados fibrilares insolúveis em forma de placas que são neurotóxicos. Adicionalmente, há produção e acúmulo de fibrilas insolúveis de tau hiperfosforilada que podem exacerbar o colapso do citoesqueleto e a desconexão sináptica.