Triglyceride-glucose index levels in patients with Klinefelter syndrome and its relationship with endothelial dysfunction and insulin resistance: a cross-sectional observational study

ABSTRACT Objectives: This study aimed to investigate the triglyceride-glucose (TyG) index, which is a simple surrogate marker of insulin resistance that is associated with various cardiometabolic diseases, in patients with Klinefelter syndrome (KS). Subjects and methods: A total of 30 patients with KS (mean age: 21.53 ± 1.66 years) and 32 healthy controls (mean age: 22.07 ± 1.01 years) were included in the study.The clinical and laboratory parameters,TyG index, asymmetric dimethylarginine (ADMA) level, homeostatic model assessment of insulin resistance (HOMA-IR) score, and high-sensitivity C-reactive protein level were measured in patients with KS and healthy subjects. Results: Patients with KS had higher HOMA-IR score (p = 0.043), ADMA levels (p < 0.001), and TyG index (p = 0.031) and lower high-density lipoprotein cholesterol levels (p < 0.001) than healthy subjects. TyG index was positively correlated with plasma ADMA (r = 0.48, p < 0.001) and HOMA-IR (r = 0.36, p = 0.011). Multivariate analyses showed that total testosterone level (β = −0.44, p = 0.001) and TyG index (β = 0.29, p = 0.045) were independent determinants of plasma ADMA levels. Conclusion: Patients with KS had higher TyG indices than healthy subjects. Moreover, TyG index was independently associated with endothelial dysfunction in patients. TyG index may be a practical and useful measure to show the increased endothelial dysfunction in patients with KS.

Body adiposity markers and insulin resistance in patients with type 1 diabetes

ABSTRACT Objectives: Body composition changes are associated with adverse effects such as increased insulin resistance (IR) in individuals with diabetes mellitus. This study aims to evaluate the association between different body adiposity markers and IR in adults with type 1 diabetes (T1D). Subjects and methods: The cross-sectional study included outpatient adults with T1D from a university public hospital in southern Brazil. The body adiposity markers studied were waist circumference (WC), waist-height ratio (WHtR), body mass index (BMI), conicity index (CI), lipid accumulation product (LAP) and body adiposity index (BAI). IR was calculated using an Estimated Glucose Disposal Rate (EGDR) equation (analyzed in tertiles), considering an inverse relation between EGDR and IR. Poisson regression models were used to estimate the odds ratio (OR) and 95% CIs of association of adiposity markers with IR. Results: A total of 128 patients were enrolled (51% women), with a median EGDR of 7.2 (4.4-8.7) mg.kg−1.min−1. EGDR was negatively correlated with WC (r = −0.36, p < 0.01), WHtR (r = −0.39, p < 0.01), CI (r = −0.44, p < 0.01), LAP (r = −0.41, p < 0.01) and BMI (r = −0.24, p < 0.01). After regression analyses, WC (OR = 2.07; CIs: 1.12-3.337; p = 0.003), WHtR (OR = 2.77; CIs: 1.59-4.79; p < 0.001), CI (OR = 2.59; CIs: 1.43-4.66; p = 0.002), LAP (OR = 2.27; CIs: 1.25-4.11; p = 0.007) and BMI (OR = 1.78; CIs: 1.09-2.91; p = 0.019) remained associated with IR. Conclusions: The authors suggest using the studied adiposity markers as a routine since they were shown to be suitable parameters in association with IR.

Impact of hepatitis C virus eradication with direct-acting antivirals on glycidic metabolism

ABSTRACT Objective: To compare the glucose metabolism of patients with chronic hepatitis C virus infection treated with direct-acting antivirals (DAAs) in pretreatment and sustained viral response (SVR) periods. Materials and methods: This was an intervention pre-post study of 273 patients with chronic hepatitis C virus infection treated with DAAs from March 2018 to December 2019. Glycidic metabolism was evaluated through homeostasis model assessment (HOMA) - insulin resistance (IR) and HOMA-β indices and assessments of insulinemia and HbA1c levels. These parameters were analyzed with a T test by paired comparison of the means of the variables and Wilcoxon's test paired for the median; in the variables with an abnormal distribution, the Z score was generated for the mean in both the pretreatment and SVR periods. Statistical significance was considered at p ≤ 0.05. Results: Among 273 participants, 125 (45.8%) had prediabetes, and 50 (18.3%) had diabetes. In SVR, there was a significant increase in platelets, albumin, alkaline phosphatase, cholesterol and triglycerides and a significant decrease in aspartate aminotransferase, alanine aminotransferase, gamma GT and bilirubin. The HOMA-IR and HOMA-β indices increased in SVR from 1.95 to 2.29 (p = 0.087) and 71.20 to 82.60 (p = 0.001), respectively. Insulinemia increased from 7.60 μU/mL to 8.90 μU/mL (p = 0.011). HbA1c decreased from 5.6 to 5.4 (p < 0.001). Among patients with prediabetes and those with diabetes, the reduction in HbA1c values was significant (p = 0.006 and p = 0.026, respectively). Conclusion: SVR significantly impacts and leads to improvement in glucose metabolism in patients with chronic liver disease induced by hepatitis C virus.

Infección grave de piel y partes blandas por Fusarium oxysporum asociado a la administración subcutánea de insulina / Severe skin and soft tissue infection due to Fusarium oxysporum associated with subcutaneous insulin administration

Resumen La diabetes mellitus (DM) es una enfermedad crónica muy prevalente. Dentro de los tratamientos para la DM se encuentra la insulina que es el agente antidiabético más potente, sin embargo, una proporción significativa de pacientes no logra alcanzar el objetivo de hemoglobina glicosilada (HbA1c). Los errores en la aplicación de insulina son un factor importante y corregible en muchos casos. Se presenta el caso de una paciente con DM, antecedentes de neuropatía diabética, enfermedad renal crónica estadio V en hemodiálisis, hipertensión arterial, estenosis aórtica con recambio por válvula protésica, y anticoagulada, con escasa adherencia a recomendaciones higiénico dietéticas. Debido a la mala técnica de aplicación de insulina y falta de higiene, desarrolló varias infecciones polimicrobianas de piel y partes blandas, con evolución tórpida de las úlceras y mala respuesta al tratamiento indicado. Durante su internación, de una úlcera se aisló Fusarium oxysporum. Es importante jerarquizar la relevancia de la educación diabetológica en pacientes insulinizados y el rol de los educadores en diabetes en el cuidado de los mismos. Por otro lado, destacar la importancia de la toma de cultivos mediante punción de partes blandas ante la aparición de signos locales de infección.

Abstract Diabetes mellitus (DM) is a very prevalent chronic disease. Among the treatments for DM, insulin is the most potent antidiabetic agent. However a significant proportion of patients fail to achieve Errors in the application of insulin are an important and correctable factor in many cases. We present the case of a patient with DM who, due to poor insulin application technique and hygiene, develops a skin and soft tissue infection with subsequent appearance of Fusarium oxysporum. It is important to emphasize the relevance of diabetes education in insulin ized patients and the role of diabetes educators in their care. On the other hand, it is important to emphasize the importance of taking cultures by soft tissue puncture in case of local signs of infection.

Gestão de riscos como melhoria para a aquisição e distribuição de insulinas pelo SUS / Risk management as an improvement for the acquisition and distribution of insulins by SUS

Objetivo: identificar a melhoria por meio da gestão de risco aplicada aos processos de aquisição e distribuição de insulinas humanas NPH. Método: O estudo foi realizado por etapas: em 1º momento foram realizadas reuniões (Brainstorming) e em 2º momento foi elaborado um formulário eletrônico em forma de questionário sendo mostrado os "eventos" de riscos com os pesos inerentes à probabilidade e ao impacto que geraram o risco inerente aos processos de aquisição e distribuição de insulinas humanas NPH e Regular pelo Ministério da Saúde. Resultados: Considerando os processos houve maior incidência de riscos médios. Não foi apontado risco muito baixo, não foi identificado risco extremo e foram apresentados apenas 02 (dois) riscos altos. Conclusão: A gestão de risco do referido estudo é uma ferramenta de melhoria para os processos de aquisição e distribuição de insulinas humanas NPH e Regular pelo Ministério da Saúde.(AU)

Objective: to identify improvement through risk management applied to the acquisition and distribution processes of NPH human insulins. Method: The study was carried out in stages: in the 1st moment, meetings were held (Brainstorming) and in the 2nd moment, an electronic form was elaborated in the form of a questionnaire, showing the risk "events" with the weights inherent to the probability and impact they generated the risk inherent in the acquisition and distribution processes of NPH and Regular human insulins by the Ministry of Health. Results: Considering the processes, there was a higher incidence of medium risks. No very low risk was indicated, no extreme risk was identified and only 02 (two) high risks were presented. Conclusion: The risk management of the aforementioned study is an improvement tool for the processes of acquisition and distribution of NPH and Regular human insulins by the Ministry of Health.(AU)

Descarte correto de resíduo doméstico de pessoas em uso de insulina: tecnologia para educação ao paciente / Correct disposal of domestic waste from people using insulin: technology for patient education / Correcta eliminación de residuos domésticos de personas que utilizan insulina: tecnología para la educación del paciente

Objetivo: Analisar as formas de descarte correto do resíduo doméstico advindo da insulinoterapia e elaborar uma tecnologia para educação aos pacientes (cartilha). Métodos: Estudo descritivo e exploratório, do tipo revisão integrativa. O levantamento das publicações foi realizado entre os meses de julho a dezembro de 2021, a partir das bases de dados Literatura Latino-Americana em ciências da saúde (Lilacs), Scientific Electronic Library Online (Scielo) e Biblioteca Virtual em Saúde (BVS), utilizando como descritores: Diabetes Mellitus; Insulina; Gerenciamento de Resíduos. Resultados: Identificou-se que a orientação a pessoa com Diabetes Mellitus quanto ao descarte correto de agulhas, seringas, lancetas, fitas reagentes, entre outros é deficiente e que a falta de legislação brasileira específica para resíduos de saúde produzidos em residências é o principal problema para o gerenciamento inadequado dos resíduos de serviços de saúde. A partir dos achados foi possível desenvolver uma tecnologia para educação a pessoas em uso de insulina. Conclusão: Há necessidade de investir em ações de orientação e prevenção, para reforçar aos usuários os cuidados no descarte dos resíduos de serviços de saúde. A capacitação dos profissionais da saúde possibilita o repasse de orientações adequadas e consistentes aos usuários, visando a proteção de quem produz os resíduos, dos coletores e do meio ambiente. (AU)

Objective: To analyze the forms of correct disposal of domestic waste from insulin therapy and develop a technology for patient education (booklet). Methods: Descriptive and exploratory study, integrative review type. The survey of publications was conducted between July and December 2021, from the Latin American Literature in Health Sciences (Lilacs), Scientific Electronic Library Online (Scielo) and Virtual Health Library (VHL) databases, using the following descriptors: Diabetes Mellitus; Insulin; Waste Management. Results: It was identified that the guidance to people with Diabetes Mellitus regarding the correct disposal of needles, syringes, lancets, reagent strips, among others is deficient and that the lack of specific Brazilian legislation for health care waste produced in households is the main problem for the inadequate management of health care waste. From the findings it was possible to develop a technology for education of people using insulin. Conclusion: There is a need to invest in guidance and prevention actions, to reinforce to users the care in the disposal of health services waste. The training of health professionals enables the transfer of appropriate and consistent guidance to users, aiming to protect those who produce waste, the collectors and the environment. (AU)

Objetivo: Analizar las formas de eliminación correcta de los desechos domésticos resultantes de la terapia con insulina y desarrollar una tecnología para la educación del paciente (cuaderno). Métodos: Estudio descriptivo y exploratorio, del tipo revisión integradora. El relevamiento de publicaciones se realizó entre julio y diciembre de 2021, a partir de las bases de datos Literatura Latinoamericana en Ciencias de la Salud (Lilacs), Biblioteca Científica Electrónica en Línea (Scielo) y Biblioteca Virtual en Salud (BVS), utilizando como descriptores: Diabetes Mellitus; Insulina; Gestión de residuos. Resultados: Se identificó que la orientación a las personas con Diabetes Mellitus sobre el correcto desecho de agujas, jeringas, lancetas, tiras reactivas, entre otros, es deficiente y que la falta de legislación brasileña específica para los desechos sanitarios producidos en los domicilios es el principal problema por la gestión inadecuada de los residuos sanitarios. Con base en los hallazgos, fue posible desarrollar una tecnología para educar a las personas que usan insulina. Conclusión: Existe la necesidad de invertir en acciones de orientación y prevención, para reforzar la atención de los usuarios en la eliminación de los residuos de los servicios de salud. La formación de los profesionales de la salud permite transmitir orientaciones adecuadas y coherentes a los usuarios, con el objetivo de proteger a los productores de residuos, a los recolectores y al medio ambiente. (AU)

The threshold value for identifying insulin resistance (HOMA-IR) in an admixed adolescent population: A hyperglycemic clamp validated study

ABSTRACT Objectives: To validate the homeostasis model assessment (HOMA) of insulin resistance (IR) as a surrogate to the hyperglycemic clamp to measure IR in both pubertal and postpubertal adolescents, and determine the HOMA-IR cutoff values for detecting IR in both pubertal stages. Subjects and methods: The study sample comprised 80 adolescents of both sexes (aged 10-18 years; 37 pubertal), in which IR was assessed with the HOMA-IR and the hyperglycemic clamp. Results: In the multivariable linear regression analysis, adjusted for sex, age, and waist circumference, the HOMA-IR was independently and negatively associated with the clamp-derived insulin sensitivity index in both pubertal (unstandardized coefficient - B = −0.087, 95% confidence interval [CI] = −0.135 to −0.040) and postpubertal (B = −0.101, 95% CI, −0.145 to −0.058) adolescents. Bland-Altman plots showed agreement between the predicted insulin sensitivity index and measured clamp-derived insulin sensitivity index in both pubertal stages (mean = −0.00 for pubertal and postpubertal); all P > 0.05. The HOMA-IR showed a good discriminatory power for detecting IR with an area under the receiver operator characteristic curve of 0.870 (95% CI, 0.718-0.957) in pubertal and 0.861 (95% CI, 0.721-0.947) in postpubertal adolescents; all P < 0.001. The optimal cutoff values of the HOMA-IR for detecting IR were > 3.22 (sensitivity, 85.7; 95% CI, 57.2-98.2; specificity, 82.6; 95% CI, 61.2-95.0) for pubertal and > 2.91 (sensitivity, 63.6; 95% CI, 30.8-89.1, specificity, 93.7; 95%CI, 79.2-99.2) for postpubertal adolescents. Conclusion: The threshold value of the HOMA-IR for identifying insulin resistance was > 3.22 for pubertal and > 2.91 for postpubertal adolescents.

Triglyceride-glucose index is associated with poor sleep quality in apparently healthy subjects: A cross-sectional study

ABSTRACT Objectives: We aimed to evaluate the association between the triglyceride glucose index (TyG index) and sleep quality and to establish a cut-off value for the TyG index based on the prevalence of subjects with insulin resistance (IR). Materials and methods: This cross-sectional study involved Brazilian health professionals (20-59 years). A total of 138 subjects answered the Pittsburgh Sleep Quality questionnaire to evaluate sleep quality. They were categorized into two groups: good sleep quality (global score ≤ 5 points) and poor sleep quality (global score ≥ 6 points). Also, we classified the subjects as having a high (>8.08 or >4.38) or low TyG index (≤8.08 or ≤4.38). Results: The majority of the subjects (70%) with high TyG index values (>8.08 or >4.38) reported poor sleep quality (p ≤ 0.001). Those with poor sleep quality had a 1.44-fold higher prevalence of IR (TyG index >8.08 or >4.38) compared to those with good sleep quality, regardless of sex, total cholesterol, LDL/HDL ratio, insulin, complement C3, CRP, and adiponectin (p ≤ 0.001). Conclusion: Our data showed a positive and significant association between the TyG index and poor sleep quality. Thus, these findings support the association between poor sleep quality and IR.

Effects of antidiabetics and exercise therapy on suppressors of cytokine signaling-1, suppressors of cytokine signaling-3, and insulin receptor substrate-1 molecules in diabetes and obesity

SUMMARY OBJECTIVE: Pathological destruction of insulin signaling molecules such as insulin receptor substrate, especially due to the increase in suppressors of cytokine signaling molecules, has been demonstrated in experimental diabetes. The contribution of suppressors of cytokine signaling proteins to the development of insulin resistance and the effects of antidiabetic drugs and exercise on suppressors of cytokine signaling proteins are not clearly known. METHODS: A total of 48 Wistar albino adult male rats were divided into six groups: control group, obese group with diabetes, obese diabetic rats treated with metformin, obese diabetic rats treated with pioglitazone, obese diabetic rats treated with exenatide, and obese diabetic rats with applied exercise program. Immunohistochemical staining was performed in both the liver and adipose tissue. RESULTS: There was a statistically significant decrease in suppressors of cytokine signaling-1, a decrease in suppressors of cytokine signaling-3, an increase in insulin receptor substrate-1, and a decrease in immunohistochemical staining in the obese group treated with metformin and exenatide compared to the obese group without treatment in the liver tissue (p<0.05). A statistically significant decrease in immunohistochemical staining of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 was found in the obese group receiving exercise therapy compared to the obese group without treatment in visceral adipose tissue (p<0.05). Likewise, no significant immunohistochemistry staining was seen in diabetic obese groups. CONCLUSION: Metformin or exenatide treatment could prevent the degradation of insulin receptor substrate-1 protein by reducing the effect of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins, especially in the liver tissue. In addition, exercise can play a role as a complementary therapy by reducing suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins in visceral adipose tissue.

Associação entre nível sérico de vitamina D e resistência à insulina em adolescentes com excesso de peso / Association between serum vitamin D level and insulin resistance in overweight adolescents

A manutenção da homeostase glicêmica e da secreção de insulina tem sido considerada um dos efeitos metabólicos da vitamina D (VD). Tradicionalmente, a obesidade é a principal causa de resistência insulínica (RI) e um importante fator de risco para a deficiência de VD. Portanto, adolescentes com obesidade e deficiência de VD podem estar diante de uma condição de dupla carga de risco para apresentar RI. Objetivou-se avaliar a associação entre os níveis séricos de 25-hidroxivitamina D [25(OH)D] e parâmetros de RI em adolescentes com excesso de peso. Trata-se de um estudo observacional em 42 adolescentes, com excesso de peso, acompanhados em serviço de atenção secundária. O excesso de peso foi definido pelos critérios da Organização Mundial da Saúde e os níveis séricos de 25(OH)D foram categorizados em normal (≥ 30 ng/mL) e baixa (< 30 ng/mL) de acordo com a Sociedade Brasileira de Nutrologia. Na avaliação da RI foram utilizados o modelo homeostático de avaliação da RI (HOMA-IR), a relação glicose/ insulina e a insulinemia de jejum. O grupo estudado caracterizou-se por ser predominantemente de adolescentes jovens (88,1% entre 10 e 14 anos), estar na puberdade (83,5%) e ter obesidade central (80%) e hipovitaminose D (85,7%). Os adolescentes com VD baixa apresentaram maior ocorrência de RI pelo índice de HOMAR IR (teste Fisher unicaudal, p < 0,05), sugerindo uma relação entre o status de vitamina D e à sensibilidade à insulina, houve associação positiva entre VD baixa e HOMA-IR elevada.

The maintenance of glycemic homeostasis and insulin secretion is considered one of the metabolic effects of vitamin D (VD). Traditionally, obesity is the main cause of insulin resistance (IR) and an important risk factor for VD deficiency. Therefore, adolescents with obesity and VD deficiency may be faced with a doubled risk of developing IR. The objective of this study was to evaluate the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and IR parameters in overweight adolescents. This is an observational study of 42 overweight adolescents followed in a secondary care service. Overweight was defined by the criteria of the World Health Organization and serum levels of 25(OH)D were categorized as normal (≥ 30 ng/mL) and low (< 30 ng/mL) according to the Brazilian Society of Nutrology. In the assessment of IR, the homeostatic model of IR assessment (HOMA-IR), the glucose/insulin ratio and fasting insulinemia were used. The studied group was characterized as being predominantly young adolescents (88.1% between 10 and 14 years old), in puberty (83.5%), and having central obesity (80%), and hypovitaminosis D (85.7%). Adolescents with low VD showed a higher occurrence of IR according to the HOMAR IR index (one-tailed Fisher test, p <0.05), suggesting a relationship between vitamin D status and insulin sensitivity; hence, there was a positive association between low VD and high HOMA-IR.

Effect of silibinin and trans-chalcone in an Alzheimer's disease-like model generated by insulin amyloids

Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.

Construção e validação de tecnologia educacional sobre insulinoterapia: estudo metodológico / Construction and validation of educational technology on insulin therapy: methodological study / Construcción y validación de tecnología educativa sobre insulinoterapia: estudio metodológico

RESUMO Objetivo: construir e validar tecnologia educacional sobre insulinoterapia para práticas educativas de profissionais de saúde. Método: estudo metodológico realizado em três etapas: construção, entre os meses de maio a setembro de 2019; e validação de conteúdo e validação de aparência, agosto de 2020 a agosto de 2021, em Universidade Pública do Amapá, Brasil. A validação de conteúdo e a validação de aparências foram realizadas em etapas únicas com 16 profissionais da área da saúde e com cinco profissionais de outras áreas respectivamente. Resultados: a tecnologia educacional foi nomeada álbum seriado sobre Insulinoterapia, estando disponível no formato impresso. Apresentou Índice de Validade de Conteúdo de 0,91 e Índice de Validade de Aparência de 1,00. Conclusão: a tecnologia foi validada e pode ser utilizada por profissionais de saúde da atenção primária em práticas educativas em saúde, com vistas à promoção de ensino-aprendizagem sobre o uso de insulina, beneficiando o processo de cuidado e comunicação na atenção à saúde.

ABSTRACT Objective: to build and validate educational technology on insulin therapy for educational practices of health professionals. Method: methodological study conducted in three stages: construction, between May and September 2019; and content validation and appearance validation, August 2020 to August 2021, in a Public University of Amapá, Brazil. Content validation and appearance validation were performed in single steps with 16 health professionals and with five professionals from other areas respectively. Results: The educational technology was named Serial Album on Insulin Therapy and was available in printed format. It presented a Content Validity Index of 0.91 and an Appearance Validity Index of 1.00. Conclusion: the technology was validated and can be used by primary care health professionals in health educational practices, with a view to promoting teaching-learning about the use of insulin, benefiting the process of care and communication in health care.

RESUMEN Objetivo: construir y validar una tecnología educativa sobre la insulinoterapia para las prácticas educativas de los profesionales de la salud. Método estudio metodológico realizado en tres etapas: construcción, entre mayo y septiembre de 2019; y validación de contenido y validación de apariencia, agosto de 2020 a agosto de 2021, en una Universidad Pública de Amapá, Brasil. La validación del contenido y la validación de la apariencia se realizaron en un solo paso con 16 profesionales de la salud y cinco profesionales de otras áreas, respectivamente. Resultados: la tecnología educativa se ha convertido en un rotafolio sobre insulinoterapia, disponible en formato impreso. Presentó un Índice de Validez de Contenido de 0,91 y un Índice de Validez de Apariencia de 1,00. Conclusión: la tecnología fue validada y puede ser utilizada por los profesionales de salud de la atención primaria en prácticas educativas en salud, con vistas a promover la enseñanza-aprendizaje sobre el uso de la insulina, beneficiando el proceso de atención y comunicación en salud.

Psychosocial factors related to the behavioral intention of people with type 2 diabetes using insulin / Fatores psicossociais correlacionados com a intenção comportamental das pessoas com diabetes mellitus tipo 2 (DM2) para uso de insulina / Factores psicosociales correlacionados con la intención conductal de personas con diabetes mellitus tipo 2 (DM2) para uso de insulina

ABSTRACT Objectives: to analyze the psychosocial factors correlated with the behavioral intention of people with Type 2 Diabetes Mellitus (T2DM) towards insulin use. Methods: a cross-sectional study; a validated instrument based on the Theory of Planned Behavior was used to identify the direct measures (attitude, subjective norm and perceived control), indirect measures (behavioral, normative and control beliefs) and behavioral intention for the use of insulin. Descriptive analysis and Spearman's correlation were performed for data analysis. Results: a total of 211 individuals participated in the study, with a positive median of behavioral intention. Attitude, normative and behavioral beliefs were the psychosocial factors that presented a significant correlation (r=0.16, r=-0,15 and r=0.25, respectively; p<0.05) with the intention. Conclusions: there is a positive behavioral intention in the use of insulin by people with T2DM. Attitude, normative beliefs and behavioral beliefs have a low magnitude correlation with the intention of people with T2DM to use insulin.

RESUMO Objetivos: analisar os fatores psicossociais correlacionados com a intenção comportamental das pessoas com diabetes mellitus tipo 2 (DM2) para uso de insulina. Métodos: estudo transversal. Instrumento validado com base na Teoria do Comportamento Planejado foi utilizado para identificar as medidas diretas (atitude, norma subjetiva e controle percebido), medidas indiretas (crenças comportamentais, normativas e de controle) e intenção comportamental para uso da insulina. Análise descritiva e correlação de Spearman foram realizadas para a análise dos dados. Resultados: um total de 211 indivíduos participaram do estudo, com uma mediana positiva de intenção comportamental. Atitude, crenças normativas e comportamentais foram os preditores que apresentaram uma correlação significante (r=0,16, r=-0,15 e r=0,25, respectivamente; p<0,05) com a intenção. Conclusões: há uma intenção comportamental positiva no uso da insulina por pessoas com DM2. Atitude, crenças Normativas e crenças comportamentais têm uma correlação de baixa magnitude com a intenção das pessoas com DM2 de usar insulina.

RESUMEN Objetivos: analizar los factores psicosociales correlacionados con la intención conductal de personas con diabetes mellitus tipo 2 (DM2) para uso de insulina. Métodos: estudio transversal. Instrumento validado basado en la Teoría de Conducta Planeada fue utilizada para identificar las medidas directas (actitud, norma subjetiva y control percibido), medidas indirectas (creencias conductuales, normativas y de control) e intención conductal para uso de insulina. Análisis descriptivo y correlación de Spearman fueron realizados para el análisis de datos. Resultados: un total de 211 individuos participaron del estudio, con una mediana positiva de intención conductal. Actitud, creencias normativas y conductuales fueron los predictores que presentaron una correlación significante (r=0,16, r=-0,15 y r=0,25, respectivamente; p<0,05) con la intención. Conclusiones: hay una intención conductal positiva en el uso de insulina por personas con DM2. Actitud, creencias Normativas y creencias conductuales tienen una correlación de baja magnitud con la intención de personas con DM2 de usar insulina.

Blood insulin level biosensor for athletes / Biossensor para nível de insulina sanguíneo em atletas / Biosensor para el nivel de insulina en sangre de deportistas

ABSTRACT Introduction: The pancreas releases insulin to assist the human body in utilizing blood glucose. It regulates metabolism by promoting the absorption of glucose into the blood. Objective: This work aimed to create an electrochemical biosensor based on magnetic graphene nanomaterial to measure insulin levels in athletes' blood. Method: A magnetic graphene nanocomposite created by graphene oxide (GO) and Fe-Ni bimetallic oxides on a glassy carbon electrode was synthesized using the electrochemical deposition method (GCE). Results: The immediate electrical deposition of Fe-Ni bimetallic oxide nanoparticles with the spherical shape on the GO nanosheet without aggregations was validated by structural characterizations of Fe-Ni/GO/GCE using XRD and SEM. The electrochemical results for insulin determination showed good sensitivity and anti-interference capability. The applicability and accuracy of the proposed electrochemical sensor to detect insulin were explored by blood serum samples from sportsmen. Conclusion: The results assigned acceptable RSD values (3.31% to 4.30%) and confirmed the feasibility of the proposed sensor for detecting athletes' blood insulin. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A insulina é liberada pelo pâncreas para auxiliar o corpo humano na utilização da glicose sanguínea. Ela regula o metabolismo, promovendo a absorção da glicose pelo sangue. Objetivo: O objetivo deste trabalho foi criar um biossensor eletroquímico baseado em nanomaterial de grafeno magnético para medir os níveis de insulina no sangue dos atletas. Método: Em um eletrodo de carbono vítreo, um nanocomposto magnético de grafeno criado por óxido de grafeno (GO) e óxidos bimetálicos de Fe-Ni foi sintetizado usando o método de deposição eletroquímica (GCE). Resultados: A deposição elétrica imediata de nanopartículas de óxido bimetal Fe-Ni com a forma esférica na nano folha GO sem agregações foi validada por caracterizações estruturais de Fe-Ni/GO/GCE utilizando XRD e SEM. Os resultados eletroquímicos para determinação da insulina demonstraram boa sensibilidade e capacidade anti-interferência. A aplicabilidade e precisão do sensor eletroquímico proposto para detectar insulina foram exploradas por amostras de soro sanguíneo dos esportistas. Conclusão: Os resultados designados para os valores aceitáveis de RSD (3,31% a 4,30%) confirmaram a viabilidade do sensor proposto para detecção de insulina sanguínea de atletas. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El páncreas libera insulina para ayudar al cuerpo humano a utilizar la glucosa en sangre. Regula el metabolismo, favoreciendo la absorción de la glucosa por la sangre. Objetivo: El objetivo de este trabajo fue crear un biosensor electroquímico basado en un nanomaterial de grafeno magnético para medir los niveles de insulina en la sangre de los deportistas. Método: Sobre un electrodo de carbono vítreo, se sintetizó un nanocompuesto de grafeno magnético creado por óxido de grafeno (GO) y óxidos bimetálicos de Fe-Ni mediante el método de deposición electroquímica (GCE). Resultados: La deposición eléctrica inmediata de las nanopartículas de óxido bimetálico Fe-Ni con forma esférica sobre la nano plancha de GO sin agregaciones fue validada por las caracterizaciones estructurales de Fe-Ni/GO/GCE mediante XRD y SEM. Los resultados electroquímicos para la determinación de la insulina mostraron una buena sensibilidad y capacidad anti-interferencia. La aplicabilidad y la precisión del sensor electroquímico propuesto para detectar la insulina se exploraron con muestras de suero sanguíneo de deportistas. Conclusión: Los resultados asignados a valores aceptables de RSD (3,31% a 4,30%) confirmaron la viabilidad del sensor propuesto para detectar la insulina en sangre de los atletas. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

The effectiveness of insulin therapy in the functional and morphological recovery of leydig cells in rats submitted to Diabetes mellitus

The effects of systemic insulin administration at different concentrations on the testicular tissue of diabetic adult rats, induced by streptozotocin, are evaluated by the morphological analysis of spermatogenic process. Twenty-four adult male rats were divided into 1) Control Group: they received citrate buffer, by intraperitoneal injection; 2) Diabetic Group: induced by intraperitoneal injection of streptozotocin (60 mg. kg-1 of body weight); 3) Insulin 50%: induced diabetes treated with half of standard dosage of insulin; 4) Insulin 100%: induced diabetes treated with standard dose of insulin. After eight weeks, animals were weighted and anesthetized; testicles were removed and processed in resin. Body and testicular weight of diabetic rats decreased when compared to that of control. Parameters increased with insulin therapy. Testosterone levels were low in diabetic animals but rates recovered after insulin therapy. Nuclear diameter and volume of Leydig cells decreased in diabetic rats although they significantly increased after insulin therapy. Results showed that the administration of insulin in diabetic rats promoted a protective effect of testicular parenchyma, enhancing efficient recovery on testosterone levels and increase in daily sperm production.

The triglyceride-glucose index as an indicator of insulin resistance and cardiometabolic risk in Brazilian adolescents

ABSTRACT Objective: To set cutoff points for the triglyceride and glucose index (TyG) as a marker of insulin resistance (IR) for the pediatric population. Subjects and methods: This was a cross-sectional study with schoolchildren population-based data using data of 377 schoolchildren age 10 to 17 years of both sexes. We studied metabolic variables associated with IR indicators, such as fasting insulin and blood glucose, to calculate the homeostatic model assessment (HOMA-IR), and we studied triglycerides (TG) to determine the TyG index. We obtained TyG cutoff values for IR using the receiver operation characteristic (ROC), with definitions of sensitivity (Sen), specificity (Spe), and area under the ROC curve (AUC), with the HOMA-IR as reference. Results: The cutoff points of the TyG index for IR in adolescents are 7.94 for both sexes, 7.91 for boys, and 7.94 for girls, indicating moderate discriminatory power. When we also considered anthropometric variables of excess weight [TyG-BMI (body mass index)] and visceral fat [TyG-WC (waist circumference)], these indexes reached AUC values higher than 0.72, enhancing their potential use for a good diagnosis. Conclusion: TyG has proven to be a useful instrument for identifying IR in adolescent health screening, with high discrimination capacity when added to anthropometric variables, making it a feasible and inexpensive option.

Liver steatosis as a predictor of incident diabetes in adults: a prospective evaluation in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) / Esteatose hepática como preditor de diabetes incidente em adultos: avaliação prospectiva no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil) / Esteatosis hepática como predictor de diabetes incidente en adultos: evaluación prospectiva en el Estudio Longitudinal de Salud del Adulto (ELSA-Brasil)

Increasing epidemiological evidence suggests a bidirectional relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, and that NAFLD may precede and/or promote the development of diabetes. This study aimed to investigate whether liver steatosis is associated with the incidence of diabetes in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The ELSA-Brasil is an occupational cohort study of active or retired civil servants, aged 35-74 years, in six capital cities in Brazil. We excluded participants with diabetes at baseline, those who reported excessive alcohol consumption or with missing information on relevant covariates, and those with self-referred hepatitis or cirrhosis. In total, 8,166 individuals participated, and the mean duration of follow-up was 3.8 years. The Cox proportional regression model was used to estimate the adjusted hazard ratio (HR) for the associations. Abdominal ultrasonography was used to detect liver steatosis. In the follow-up period, the cumulative incidence of diabetes was 5.25% in the whole sample, 7.83% and 3.88% in the groups with and without hepatic steatosis, respectively (p < 0.001). Compared to those without steatosis, individuals with hepatic steatosis had an increased risk of developing diabetes (HR = 1.31; 95%CI: 1.09-1.56) after adjustment for potential confounders, including body mass index (BMI). Hepatic steatosis was an independent predictor of incident diabetes in the ELSA-Brasil cohort study. Physicians should encourage changes in lifestyle and screen for diabetes in patients with fatty liver.

Evidências epidemiológicas crescentes sugerem uma relação bidirecional entre a doença hepática gordurosa não alcoólica (DHGNA) e o diabetes tipo 2 e que a DHGNA pode preceder e/ou promover o desenvolvimento de diabetes. O objetivo deste estudo foi investigar se a esteatose hepática está associada à incidência de diabetes no Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). O ELSA-Brasil é um estudo de coorte ocupacional com servidores públicos ativos ou aposentados, com idades entre 35 e 74 anos, de seis capitais do Brasil. Foram excluídos os participantes com diabetes no início do estudo, aqueles que relataram consumo excessivo de álcool ou com falta de informações sobre covariáveis relevantes e indivíduos com hepatite ou cirrose autorreferida. No total, 8.166 indivíduos participaram e o tempo médio de seguimento foi de 3,8 anos. O modelo de regressão proporcional de Cox foi utilizado para estimar a razão de risco (HR) ajustada para as associações. A ultrassonografia abdominal foi utilizada para detectar esteatose hepática. No período de seguimento, a incidência cumulativa de diabetes foi de 5,25% em todo o grupo de participantes e de 7,83% e 3,88% nos grupos com e sem esteatose hepática, respectivamente (p < 0,001). Em comparação com aqueles sem esteatose, os indivíduos com esteatose hepática apresentaram um risco elevado de desenvolver diabetes (HR = 1,31; IC95%: 1,09-1,56) após o ajuste para potenciais fatores de confusão, incluindo o índice de massa corporal (IMC). A esteatose hepática foi um preditor independente de diabetes incidente no ELSA-Brasil. Os médicos devem incentivar mudanças no estilo de vida e a triagem para diabetes para pacientes com fígado gorduroso.

La creciente evidencia epidemiológica sugiere una relación bidireccional entre la enfermedad del hígado graso no alcohólica (EHGNA) y la diabetes tipo 2 y que la EHGNA puede preceder y/o desarrollar la diabetes. El objetivo de este estudio fue investigar si la esteatosis hepática está asociada con la incidencia de diabetes en el Estudio Longitudinal de Salud del Adulto (ELSA-Brasil). ELSA-Brasil es un estudio de cohorte ocupacional, realizado con funcionarios públicos activos o jubilados, con edades entre 35 y 74 años, de seis capitales en Brasil. Se excluyeron a los participantes con diabetes al inicio del estudio, aquellos que informaron consumir excesivamente alcohol o que carecían de información sobre las covariables relevantes, y los individuos con hepatitis o cirrosis autorreportada. En total participaron 8.166 sujetos, y el tiempo medio de seguimiento fue de 3,8 años. Se utilizó el modelo de regresión proporcional de Cox para estimar la razón de riesgo ajustada (HR) en las asociaciones. Se realizó ecografía abdominal para detectar esteatosis hepática. En el periodo de seguimiento, el grupo de participantes tuvo incidencia acumulada de diabetes del 5,25%, y en los grupos con y sin esteatosis hepática fueron del 7,83% y el 3,88%, respectivamente (p < 0,001). Los individuos con enfermedad de hígado graso tuvieron mayor riesgo de desarrollar diabetes (HR = 1,31; IC95%: 1,09-1,56) después de ajustar los posibles factores de confusión, incluido el índice de masa corporal (IMC), en comparación con aquellos sin esteatosis. La esteatosis hepática fue un predictor independiente de diabetes incidente en ELSA-Brasil. Los médicos deben alentar cambios en el estilo de vida y la detección de diabetes a los pacientes con hígado graso.

New drug for thyroid-associated ophthalmopathy——Teprotumumab-trbw / 国际眼科杂志(Guoji Yanke Zazhi)

Teprotumumab-trbw,a monoclonal antibody that acts on the insulin growth factor-Ⅰ receptor, was approved in 2020 for the treatment of thyroid-associated ophthalmopathy, but little is known about it in China. It is hoped to provide guidance for clinical use through the review of its molecular structure, pharmacokinetics, therapeutic mechanism, clinical research and safety. It inhibits immune inflammation by blocking thyroid-stimulating hormone receptor /insulin growth factor-Ⅰ receptor crosstalk signaling, so as to reduce the production of hyaluronic acid and inflammatory factors in response. It can also promote the apoptosis of retro-orbital fibroblasts/adipocytes and inhibit the expression of genes related to the synthesis of thyroid hormones, thereby significantly improving the clinical symptoms such as exophthalmos and diplopia. The common adverse reactions of Teprotumumab-trbw are muscle spasm, hyperglycemia, hearing loss and so on. Teprotumumab-trbw is effective and durable in the treatment of thyroid-associated ophthalmopathy, and patients with secondary treatment can also benefit from it, which provides a new way and hope for the treatment of thyroid-associated ophthalmopathy.

Exploration of Mechanism of Xiaonang Tiaojing Decoction in Treating PCOS-IR Model Rats Based on AMH/AMHR ⅡSignaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Xiaonang Tiaojing decoction（XNTJD）in improving polycystic ovary syndrome with insulin resistance（PCOS-IR）model rats based on anti-Müllerian hormone（AMH）/AMH type Ⅱ receptor（AMHRⅡ）signaling pathway. MethodForty-eight adult female SD rats were randomly divided into the blank group， model group， XNTJD group（11.4 g·kg-1·d-1） and Diane-35 group（0.21 g·kg-1·d-1）， PCOS-IR model was established by high-fat and high-sugar diet combined with letrozole in rats of all groups except the blank group， rats in the administration groups were given the corresponding dose of drugs by gavage for 15 days with an interval of 1 d every 4 d， normal saline of the same volume was given to the blank group and the model group. Estrous cycle was recorded daily during treatment. At the end of treatment， body weight and Lee's index were recorded， AMH， luteinizing hormone（LH）， LH/follicle stimulating hormone（FSH）， testosterone（T）and estradiol（E2）levels were measured by enzyme-linked immunosorbent assay（ELISA）， fasting plasma glucose（FPG）was measured by glucometer， fasting insulin（FINS） level was measured by radioimmunoassay（RIA）， and the insulin resistance index（HOMA-IR） and insulin sensitivity index（QUICKI）were calculated， triglyceride（TG）and total cholesterol（TC）levels were measured by automatic biochemical analyzer， hematoxylin-eosin（HE）staining was used to observe the morphological changes of the ovary， the levels of AMHRⅡ， bone morphogenetic protein-15（BMP-15）and Smad5 in ovarian tissues were detected by immunohistochemistry（IHC），Western blot was used to analyze the protein expression levels of AMHRⅡ， BMP-15 and Smad5. ResultCompared with the blank group， a large number of leukocytes were observed in the vaginal exfoliated cells of rats in the model group， mainly in diestrus， the levels of body weight， Lee's index， glucose-lipid metabolism indexes（FPG， FINS， HOMA-IR， TG， TC）， AMH and sex hormones（LH， LH/FSH， T）were significantly increased（P<0.01）， and QUICKI and E2 levels were significantly decreased（P<0.01）， there were more cystic bulges on the ovarian surface， more wet weight， more atretic and cystic dilated follicles in the ovarian tissues， and the thickness of granulosa cell layer was reduced without oocytes， the expression level of AMHRⅡ protein in ovarian tissues was significantly increased（P<0.01）， and the expression levels of BMP-15 and Smad5 proteins were significantly decreased（P<0.01）. Compared with the model group， the exfoliated cells in the vagina of rats treated with XNTJD group showed keratinocytes from the 5th to 6th day of treatment， and a stable estrous cycle gradually appeared， body weight， Lee's index， glucose-lipid metabolism indexes（FPG， FINS， HOMA-IR， TG， TC）， AMH and sex hormones（LH， LH/FSH， T）levels were significantly decreased（P<0.05， P<0.01）， QUICKI and E2 levels were significantly increased（P<0.01）， ovarian surface was smoother and lighter in wet weight， oocytes and mature follicles were observed in ovarian tissues， the thickness of granulosa cell layer increased and the morphology was intact， the expression levels of BMP-15 and Smad5 proteins were significantly increased（P<0.01）and the expression level of AMHRⅡ protein was significantly decreased（P<0.01）in ovarian tissues. ConclusionXNTJD may mediate the up-regulation of BMP-15 and Smad5 in ovarian tissues of PCOS-IR rats by down-regulating AMH/AMHRⅡ， thereby improving ovarian function， sex hormones and glucose-lipid metabolism levels in PCOS-IR rats.

Effect of Tangbikang Granules on PI3K Pathway in Type 2 Diabetic Mellitus Rats with Non-alcoholic Fatty Liver Disease / 中国实验方剂学杂志

ObjectiveThis study aims to investigate the therapeutic effect of Tangbikang granules（TBK） on type 2 diabetes mellitus （T2DM） complicated with non-alcoholic fatty liver disease （NAFLD） and to elucidate the underlying mechanism. MethodT2DM and NAFLD were induced in ZDF rats， which were then respectively treated （ig） with low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK for 12 weeks. Fasting blood glucose （FBG） and body mass were recorded every 4 weeks during the treatment. One week before sampling， the feed intake of rats was detected， and after 12 h night fasting， oral glucose tolerance test （OGTT） was performed. The area under the curve （AUC） was used to evaluate glucose tolerance， and the homeostatic model assessment for insulin resistance （HOMA-IR） was calculated. Blood in abdominal aorta and liver were collected for determination of blood glucose and lipid metabolism indexes： Fasting serum insulin （FINS）， serum total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C）， high density lipoprotein cholesterol （HDL-C）， and nonesterified fatty acids （NEFA）. The liver was weighed to calculate the liver index， and the liver tissue morphology was observed and analyzed based on hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. The protein levels of insulin receptor substrate （IRS）， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt） and phosphorylated IRS and Akt were detected by Western blotting. All data were analyzed by SPSS 20.0. ResultThe feed intake of the model group was higher than that in the normal group （P<0.01）， and the feed intake the administration groups was lower than that in the model group （P<0.05， P<0.01）. At the 8th and 12th week， the body mass in the model group was lower than that in the normal group （P<0.01）. Compared with the model group， TBK reduced FBG in a concentration-dependent manner. The blood glucose level in OGTT and AUC in the model group were higher/larger than those in the normal group （P<0.01）. The blood glucose value in OGTT was decreased in TBK groups and the metformin group compared with that in the model group， and AUC in the administration groups was significantly different from that in the model group （P<0.01）. The serum level of FINS and HOMA-IR in the model group were higher than those in the normal group （P<0.01）， and they were lower in the TBK groups than in the model group （P<0.01）. Serum levels of TG， TC， HDL-C， NEFA （P<0.05， P<0.01）， and LDL-C were higher in the model group than in the normal group. Serum levels of TG， TC， LDL-C， and NEFA in the TBK groups were lower than those in the model group， and the levels of TG， LDL-C， and NEFA in TBK groups were concentration-dependent （lowest levels in high-dose TBK group）. Compared with the model group， high-dose TBK significantly increased the level of HDL-C （P<0.05）. Liver index of the model group was higher than that in the normal group （P<0.01）. The liver index of the administration groups showed a decreasing trend with no significant difference from that in the model group. As for the HE staining result of liver， the model group had unclear structure of liver lobule， enlarged cells of different sizes， and obvious steatosis of hepatocytes. TBK of all doses alleviated liver injury， particularly the high dose. For the PAS staining， compared with the normal group， the model group demonstrated significant fat vacuoles and significant reduction in purplish red glycogen granules in the cytoplasm. The staining results of high- and medium-dose groups of TBK were more similar to the normal group. Western blot was used to detect the protein expression of liver tissue. The expression of PI3K protein， p-IRS1/IRS1， and p-Akt/Akt in the model group were lower than those in the normal group （P<0.01）， and they were higher in the high-dose TBK group than in the model group （P<0.01）. ConclusionTBK exerts therapeutic effect on T2DM combined with NAFLD in ZDF rats by activating the typical PI3K signaling pathway.