Evaluación del efecto de la liposucción con o sin abdominoplastia sobre la resistencia a la insulina en pacientes normoglucémicas con sobrepeso: un estudio prospectivo de cohorte / The effect of liposuction versus liposuction with abdominoplasty on insulin resistance in normoglycemic non-obese females: A prospective cohort study

Introducción: Varios estudios han evaluado el efecto de la liposucción o de la abdominoplastia sobre la salud metabólica, incluyendo la resistencia a la insulina, con resultados mixtos. A varias pacientes con sobrepeso, sin obesidad marcada, se les recomienda el procedimiento de liposucción combinado con abdominoplastia, sin que exista publicada evidencia alguna sobre la efectividad de combinar ambos procedimientos en la salud metabólica. Métodos: El presente estudio prospectivo de cohorte evaluó el cambio en la resistencia a la insulina y otros parámetros metabólicos en dos grupos de mujeres hispanoamericanas normoglucémicas con sobrepeso. Las pacientes del primer grupo fueron sometidas a liposucción únicamente (LIPO), mientras que el segundo grupo fue sometido a liposucción con abdominoplastia (LIPO+ABDO). Resultados: Un total de 31 pacientes fueron evaluadas, incluyendo a 13 con LIPO y 18 con LIPO+ABDO; ambos grupos mostraron HOMA-IR prequirúrgicos similares (p>0,72). En las del grupo LIPO evaluadas 60días después del procedimiento, se observaron HOMA-IR similares a sus niveles prequirúrgicos (2.,98±0,4 vs. 2,70±0,3, p>0,20); las del grupo LIPO+ABDO, sin embargo, mostraron HOMA-IR significativamente reducidos en comparación de sus índices prequirúrgicos (2,37±0,2 vs. 1,73±0,1, p<0,001). También en este grupo, esta reducción se correlacionó positivamente con el valor prequirúrgico de HOMA-IR (p<0,001) y, de manera interesante, se observó una correlación negativa entre la edad de la paciente y el grado de disminución en el HOMA-IR tras la cirugía (Spearman r=−0,56, p<0,05). No se observaron cambios en los otros parámetros bioquímicos evaluados. Conclusiones: Los datos de este estudio sugieren que cuando es combinada con abdominoplastia, la liposucción mejora la resistencia a la insulina en pacientes hispanoamericanas. Se requieren de estudios adicionales para probar dicha posibilidad.(AU)

Introduction: Several studies have evaluated the effect of liposuction or abdominoplasty on metabolic health, including insulin resistance, with mixed results. Many overweight patients, with no marked obesity, are recommended to undergo liposuction combined with abdominoplasty, but no study has evaluated the effectiveness of combining the two procedures on metabolic health. Methods: The present prospective cohort study compares the metabolic parameters of two groups of normoglycemic Hispanic women without obesity. The first group underwent liposuction only (LIPO), while the second group had combined liposuction and abdominoplasty (LIPO+ABDO). Results: A total of 31 patients were evaluated, including 13 in the LIPO group and 18 in the LIPO+ABDO group. The two groups had similar HOMA-IR before surgery (P>.72). When tested 60days after surgery, women in the LIPO group had similar HOMA-IR compared to their preoperative levels (2.98±0.4 vs. 2.70±0.3; P>.20). However, the LIPO+ABDO group showed significantly reduced HOMA-IR values compared to their preoperative levels (2.37±0.2 vs. 1.73±0.1; P<.001). In this group, this decrease also positively correlated with their preoperative HOMA-IR (Spearman r=0.72; P<.001) and, interestingly, we observed a negative correlation between the age of the subjects and the drop in HOMA-IR after surgery (Spearman r=−0.56; P<.05). No changes were observed in the other biochemical parameters that were assessed. Conclusions: These data suggest that, when combined with abdominoplasty, liposuction does improve insulin resistance in healthy Hispanic females. More studies are warranted to address this possibility.(AU)

Dispositivos médicos en pacientes diabéticos y dermatitis de contacto / Medical Devices in Patients With Diabetes and Contact Dermatitis

El desarrollo y comercialización de los sensores de glucosa y las bombas de insulina han supuesto una revolución en el control de los pacientes diabéticos. En los últimos años se han detectado múltiples casos de dermatitis de contacto relacionados con estos dispositivos médicos, con el creciente interés sobre los alérgenos responsables de la sensibilización. Isobornil acrilato fue sin duda el alérgeno principal del dispositivo FreeStyle, motivando al fabricante a modificar la composición eliminando este alérgeno. Curiosamente, este alérgeno está presente en casi todos los sensores comercializados. La colofonia y derivados del ácido abiético desempeñan un papel relevante en cuanto al adhesivo. Recientemente aparecen nuevos componentes identificados como alérgenos, no comercializadas, como el dipropilene glicol diacrilato, la N,N-dimetilacrilamida, o el metacrilato de trietilenglicol, que están siendo foco de estudio. El impacto positivo que tiene el uso de estos dispositivos puede verse mermado por la sensibilización a uno de sus ingredientes, obligando en ocasiones a abandonar el dispositivo, y por ende, restando calidad de vida. El dermatólogo debe posicionarse respecto al estudio dirigido de estos pacientes, dando soporte a los servicios de endocrinología, con la finalidad de orientar tanto el cuidado de la piel como las alternativas posibles, especialmente con la colaboración de los fabricantes.(AU)

The development and commercialization of glucose sensors and insulin pumps has revolutionized the management of diabetes. These devices have been linked to multiple cases of contact dermatitis in recent years, however, giving rise to a growing interest in identifying the sensitizing allergens. Isobornyl acrylate was clearly identified as one of the main allergens responsible for contact dermatitis among users of the FreeStyle glucose sensor and was subsequently removed from the product ingredients. Remarkably, however, it is still used in most other sensors on the market. The common adhesive ingredients colophony and abietic acid derivatives have also been shown to be sensitizing agents. New components under study, such as dipropylene glycol diacrylate, N,N-dimethylacrylamide, and triethylene glycol methacrylate have recently been identified as allergens, though they are not commercially available for clinical testing. The benefits offered by glucose sensors and insulin pumps may be offset by sensitization to product ingredients, in some cases forcing discontinuation and diminishing quality of life. Dermatologists should play a role in this clinical and research scenario, offering case-by-case guidance to endocrinologists on skin care and possible alternatives for patients with glucose sensors and insulin pumps who develop contact dermatitis. They should also collaborate with the manufacturers developing these devices.(AU)

[Translated article] Medical Devices in Patients With Diabetes and Contact Dermatitis / Dispositivos médicos en pacientes diabéticos y dermatitis de contacto

El desarrollo y comercialización de los sensores de glucosa y las bombas de insulina han supuesto una revolución en el control de los pacientes diabéticos. En los últimos años se han detectado múltiples casos de dermatitis de contacto relacionados con estos dispositivos médicos, con el creciente interés sobre los alérgenos responsables de la sensibilización. Isobornil acrilato fue sin duda el alérgeno principal del dispositivo FreeStyle, motivando al fabricante a modificar la composición eliminando este alérgeno. Curiosamente, este alérgeno está presente en casi todos los sensores comercializados. La colofonia y derivados del ácido abiético desempeñan un papel relevante en cuanto al adhesivo. Recientemente aparecen nuevos componentes identificados como alérgenos, no comercializadas, como el dipropilene glicol diacrilato, la N,N-dimetilacrilamida, o el metacrilato de trietilenglicol, que están siendo foco de estudio. El impacto positivo que tiene el uso de estos dispositivos puede verse mermado por la sensibilización a uno de sus ingredientes, obligando en ocasiones a abandonar el dispositivo, y por ende, restando calidad de vida. El dermatólogo debe posicionarse respecto al estudio dirigido de estos pacientes, dando soporte a los servicios de endocrinología, con la finalidad de orientar tanto el cuidado de la piel como las alternativas posibles, especialmente con la colaboración de los fabricantes.(AU)

The development and commercialization of glucose sensors and insulin pumps has revolutionized the management of diabetes. These devices have been linked to multiple cases of contact dermatitis in recent years, however, giving rise to a growing interest in identifying the sensitizing allergens. Isobornyl acrylate was clearly identified as one of the main allergens responsible for contact dermatitis among users of the FreeStyle glucose sensor and was subsequently removed from the product ingredients. Remarkably, however, it is still used in most other sensors on the market. The common adhesive ingredients colophony and abietic acid derivatives have also been shown to be sensitizing agents. New components under study, such as dipropylene glycol diacrylate, N,N-dimethylacrylamide, and triethylene glycol methacrylate have recently been identified as allergens, though they are not commercially available for clinical testing. The benefits offered by glucose sensors and insulin pumps may be offset by sensitization to product ingredients, in some cases forcing discontinuation and diminishing quality of life. Dermatologists should play a role in this clinical and research scenario, offering case-by-case guidance to endocrinologists on skin care and possible alternatives for patients with glucose sensors and insulin pumps who develop contact dermatitis. They should also collaborate with the manufacturers developing these devices.(AU)

Antidiabéticos orales y trastornos depresivos: ¿riesgo o protección? / Oral antidiabetics and depressive disorders: Risk or protection?

Introducción la diabetes mellitus y los trastornos del estado de ánimo son 2 entidades que se entrelazan entre sí con mecanismos fisiopatológicos en común. Los hipoglucemiantes orales son un pilar fundamental para obtener el control glucémico en los individuos diabéticos y, recientemente, la alta prevalencia de estas 2 patologías en un mismo paciente han hecho que los estudios clínicos se enfoquen en analizar el efecto de los hipoglucemiantes orales en los pacientes con diabetes mellitus tipo 2 y trastorno depresivo. Objetivo realizar una revisión de la literatura disponible sobre la medicación hipoglucemiante en el contexto de los pacientes con diabetes mellitus y trastorno depresivo. Conclusiones si bien los antidiabéticos orales han mostrado tener un efecto antidepresivo en ciertos modelos experimentales, en la práctica clínica la evidencia es escasa, pero llama particularmente la atención el menor riesgo de depresión con ciertos antidiabéticos dejando abierta las posibilidades de futuros estudios con la naturaleza adecuada que permita aclarar el efecto de los hipoglucemiantes orales en la población con diabetes mellitus y trastorno depresivo. (AU)

Introduction Diabetes mellitus and mood disorders are two entities that are intertwined with common pathophysiological mechanisms. Oral hypoglycemic agents are a fundamental pillar in obtaining adequate glucose control in diabetic individuals and, recently, the high prevalence of these two pathologies in the same patient have led clinical studies to focus on analyzing the effect of oral hypoglycemic agents in diabetics. patients with type 2 diabetes mellitus and depressive disorder. Objective To carry out a review of the available literature on hypoglycemic medication in the context of patients with diabetes mellitus and depressive disorder. Conclusions Although oral antidiabetics have been shown to have an antidepressant effect in certain experimental models, in clinical practice the evidence is scarce, but the lower risk of depression with certain antidiabetics is particularly noteworthy, leaving open the possibilities of future studies with the adequate nature that allows clarifying the effect of oral hypoglycemic agents in the population with diabetes mellitus and depressive disorder. (AU)

Clinical, glycometric features and treatment in a family with monogenic diabetes due to a new mutation in the insulin gene.

Monogenic diabetes caused by changes in the gene that encodes insulin (INS) is a very rare form of monogenic diabetes (<1%). The aim of this work is to describe the clinical and glycaemic control characteristics over time from four members of a family diagnosed with monogenic diabetes with the novel mutation: c.206del,p.(Gly69Aalfs*62) located in exon 3 of the gene INS. 75% are females, with debut in adolescence and negative autoimmunity. In all cases, C-peptide is detectable decades after diagnosis (>0.6ng/ml). Currently, patients are being treated either with insulin in a bolus-basal regimen, oral antidiabetics or hybrid closed loop system. Monogenic diabetes due to mutation in the INS is an entity with heterogeneous presentation, whose diagnosis requires high suspicion and presents an important clinical impact. Given the lack of standards in this regard, therapy must be individualized, although insulin therapy could help preserve beta cell functionality in these subjects.

An effective insulin infusion protocol for severe traumatic brain injury patients: A retrospective observational study.

PURPOSE: Severe traumatic brain injury (sTBI) patients often experience stress hyperglycaemia, which can lead to negative outcomes. This study aims to introduce an effective insulin infusion protocol specifically designed for sTBI patients. METHODS: Data was collected from all sTBI patients during two periods: 1 October 2019 to 30 April 2020, and 1 June 2020 to 31 December 2020. In May 2020, a new insulin infusion protocol was implemented. Blood glucose management, infection, coagulation, and prognosis were compared in these two periods. RESULT: 195 patients were included, with 106 using the new protocol. The proportion of hyperglycaemia decreased from 40.04% to 26.91% (P<0.05), and the proportion of on-target blood glucose levels increased from 35.69% to 38.98% (P<0.05). Average blood glucose levels decreased from 9.98±2.79mmol/L to 8.96±2.82mmol/L (P<0.05). There was no substantial increase in hypoglycaemia, which remained controlled below 1%. The new protocol positively influenced glucose concentration and dispersion trends. There were no significant differences in catheter-related infections, antibiotic use, mechanical ventilation (MV) duration, length of stay in ICU, Glasgow Outcome Scale (GOS), or mortality. However, the conventional protocol group had a higher coagulation tendency (R-value of thromboelastography 4.80±1.35min vs. 5.52±1.87min, P<0.05), with no difference in deep vein thrombosis (DVT) incidence. CONCLUSION: Our findings suggest that a customized insulin infusion process for sTBI patients can effectively manage blood glucose. While there is no significant improvement in infection control or prognosis, it may have a positive impact on coagulation without affecting the occurrence of DVT.

High fat diet- induced obesity decreases ErbB receptors expression in liver and adipose tissue in C57BL/6 mice

Neuregulins (NRGs) are a family of signaling proteins that bind to receptor tyrosine kinases of the ErbB family (ErbB2 to ErbB4), which can homo- or heterodimerize depending on their structural features and cell type. Many studies have proposed that decreased NRG levels are a common characteristic of obesity. In liver and adipose tissue, the increase in NRG expression has protective effects against obesity. However, it is still unknown whether ErbBs expression is altered in this pathology. We hypothesized that high fat diet-induced obesity downregulates ErbB receptors expression in obese mice compared to normal weight mice. Males C57BL/6 mice (n=6-7 for each group) were fed for 12 weeks and divided into: (i) control diet (CD; 10%-kcal fat, 20%-kcal protein, 70%-kcal carbohydrates), and (ii) high fat diet (HFD; 60%-kcal fat, 20%-kcal protein, 20%-kcal carbohydrates). General parameters and ErbBs expression (qPCR, immunohistochemistry and Western blot) were evaluated. We observed a significant increase in final body weight (47%), adipose tissue to body weight ratio (244%) and HOMA-IR (69%), among other parameters, in obese mice. In HFD group significantly decreased ErbB2 (48%) and ErbB3 (66%) mRNA levels in liver (no change in ErbB4), and ErbB2 (43%), ErbB3 (76%) and ErbB4 (35%) in adipose tissue, compared to CD. Furthermore, ErbB2 and ErbB3 protein levels decreased significantly in HFD group compared to the CD in liver. Therefore, our results suggest that HFD-induced obesity significantly decreases ErbBs expression in liver and adipose tissue in this murine model, that may be associated with alterations in the NRG pathway in obese mice.

Las neuregulinas (NRGs) son una familia de proteínas de señalización que se unen a receptores tirosina quinasas de la familia ErbB (ErbB2 a ErbB4), que pueden homo- o heterodimerizar dependiendo de sus características estructurales y del tipo celular. Estudios han propuesto que la disminución de los niveles de NRG es una característica común de la obesidad. En el hígado y el tejido adiposo (TA), el aumento de la expresión de NRG tiene efectos protectores contra la obesidad. Sin embargo, aún se desconoce si la expresión de ErbBs está alterada en esta patología. Nuestra hipótesis es que la obesidad inducida por una dieta alta en grasas (DAG) disminuye la expresión de los ErbB en ratones obesos. Ratones machos C57BL/6 (n=6-7 para c/grupo) fueron alimentados durante 12 semanas y divididos en: (i) dieta control (DC; 10%-kcal grasa, 20%-kcal proteína, 70%-kcal carbohidratos), y (ii) DAG (60%-kcal grasa, 20%-kcal proteína, 20%-kcal carbohidratos). Se evaluaron los parámetros generales y la expresión de ErbBs (qPCR, inmunohistoquímica y Western blot). Observamos un aumento significativo del peso corporal final (47%), de la relación tejido adiposo/peso corporal (244%) y del HOMA-IR (69%), entre otros parámetros, en ratones obesos. En este grupo disminuyó significativamente los niveles de ARNm de ErbB2 (48%) y ErbB3 (66%) en el hígado (sin cambios en ErbB4), y de ErbB2 (43%), ErbB3 (76%) y ErbB4 (35%) en el TA. Además, los niveles de proteína ErbB2 y ErbB3 disminuyeron significativamente, en comparación con el grupo DC en el hígado. Nuestros resultados sugieren que la obesidad inducida por DAG disminuye significativamente la expresión de ErbBs en el hígado y el TA, que puede estar asociado con alteraciones en la vía NRG en ratones obesos.

The effect of liposuction versus liposuction with abdominoplasty on insulin resistance in normoglycemic non-obese Mexican females: A prospective cohort study.

INTRODUCTION: Several studies have evaluated the effect of liposuction or abdominoplasty on metabolic health, including insulin resistance, with mixed results. Many overweight patients, with no marked obesity, are recommended to undergo liposuction combined with abdominoplasty, but no study has evaluated the effectiveness of combining the two procedures on metabolic health. METHODS: The present prospective cohort study compares the metabolic parameters of 2 groups of normoglycemic Hispanic women without obesity. The first group underwent liposuction only (LIPO), while the second group had combined liposuction and abdominoplasty (LIPO + ABDO). RESULTS: A total of 31 patients were evaluated, including 13 in the LIPO group and 18 in the LIPO + ABDO group. The 2 groups had similar HOMA-IR before surgery (P > 0.72). When tested 60 days after surgery, women in the LIPO group had similar HOMA-IR compared to their preoperative levels (2.98 ± 0.4 vs 2.70 ± 0.3; P > .20). However, the LIPO+ABDO group showed significantly reduced HOMA-IR values compared to their preoperative levels (2.37 ± 0.2 vs 1.73 ± 0.1; P < .001). In this group, this decrease also positively correlated with their preoperative HOMA-IR (Spearman r = 0.72; P < .001) and, interestingly, we observed a negative correlation between the age of the subjects and the drop in HOMA-IR after surgery (Spearman r = -0.56; P < .05). No changes were observed in the other biochemical parameters that were assessed. CONCLUSIONS: These data suggest that, when combined with abdominoplasty, liposuction does improve insulin resistance in healthy Hispanic females. More studies are warranted to address this possibility.

[Translated article] Medical Devices in Patients With Diabetes and Contact Dermatitis.

The development and commercialization of glucose sensors and insulin pumps has revolutionized the management of diabetes. These devices have been linked to multiple cases of contact dermatitis in recent years, however, giving rise to a growing interest in identifying the sensitizing allergens. Isobornyl acrylate was clearly identified as one of the main allergens responsible for contact dermatitis among users of the FreeStyle glucose sensor and was subsequently removed from the product ingredients. Remarkably, however, it is still used in most other sensors on the market. The common adhesive ingredients colophony and abietic acid derivatives have also been shown to be sensitizing agents. New components under study, such as dipropylene glycol diacrylate, N,N-dimethylacrylamide, and triethylene glycol methacrylate have recently been identified as allergens, though they are not commercially available for clinical testing. The benefits offered by glucose sensors and insulin pumps may be offset by sensitization to product ingredients, in some cases forcing discontinuation and diminishing quality of life. Dermatologists should play a role in this clinical and research scenario, offering case-by-case guidance to endocrinologists on skin care and possible alternatives for patients with glucose sensors and insulin pumps who develop contact dermatitis. They should also collaborate with the manufacturers developing these devices.

Anti-hyperglycemic and anti-hyperlipidemic effects of a methanolic extract of Debregeasia salicifolia in Alloxan-induced diabetic albino mice

Abstract Diabetes mellitus (DM), an endocrine syndrome characterized by high blood glucose levels due to abrogated insulin activity. The existing treatments for DM have side effects and varying degrees of efficacy. Therefore, it is paramount that novel approaches be developed to enhance the management of DM. Therapeutic plants have been accredited as having comparatively high efficacy with fewer adverse effects. The current study aims to elucidate the phytochemical profile, anti-hyperlipidemic, and anti-diabetic effects of methanolic extract D. salicifolia (leaves) in Alloxan-induced diabetic mice. Alloxan was injected intraperitoneally (150 mg kg-1, b.w), to induced diabetes in mice. The mice were divided into three groups (n=10). Group 1 (normal control) received normal food and purified water, Group II (diabetic control) received regular feed and clean water and group III (diabetic treated) received a methanolic extract of the plant (300 mg kg-1) for 28 days with a typical diet and clean water throughout the experiment. Blood samples were collected to checked serum glucose and concentration of LDL, TC, TG. The extract demonstrated significant antihyperglycemic activity (P 0.05), whereas improvements in mice's body weight and lipid profiles were observed after treatment with the extract. This study establishes that the extract has high efficacy with comparatively less toxicity that can be used for DM management.

Resumo Diabetes mellitus (DM) é uma síndrome endócrina caracterizada por níveis elevados de glicose no sangue devido à atividade anulada da insulina. Os tratamentos existentes para o DM têm efeitos colaterais e vários graus de eficácia. Portanto, é fundamental que novas abordagens sejam desenvolvidas para aprimorar o manejo do DM. As plantas terapêuticas foram acreditadas como tendo eficácia comparativamente alta com menos efeitos adversos. O presente estudo visa elucidar o perfil fitoquímico, efeitos anti-hiperlipidêmicos e antidiabéticos do extrato metanólico de D. salicifolia (folhas) em camundongos diabéticos induzidos por aloxana. Alloxan foi injetado por via intraperitoneal (150 mg kg-1, b.w), para induzir diabetes em camundongos. Os camundongos foram divididos em três grupos (n = 10). Grupo 1 (controle normal) recebeu ração normal e água purificada, Grupo II (controle diabético) recebeu ração regular e água limpa, e o grupo III (tratamento diabético) recebeu extrato metanólico da planta (300 mg kg-1) por 28 dias com uma dieta típica e água limpa durante todo o experimento. Amostras de sangue foram coletadas para verificar a glicose sérica e a concentração de LDL, TC, TG. O extrato demonstrou atividade anti-hiperglicêmica significativa (P 0,05), enquanto melhorias no peso corporal e no perfil lipídico dos camundongos foram observadas após o tratamento com o extrato. Este estudo estabelece que o extrato tem alta eficácia com comparativamente menos toxicidade e pode ser usado para o controle do DM.

Brain insulin resistance and Alzheimer's disease: a systematic review / Resistência insulínica cerebral e a doença de Alzheimer: uma revisão sistemática

ABSTRACT. The disability of cells to react to insulin, causing glucose intolerance and hyperglycemia, is referred to as insulin resistance. This clinical condition, which has been well-researched in organs such as adipose tissue, muscle, and liver, has been linked to neurodegenerative diseases like Alzheimer's disease (AD) when it occurs in the brain. Objective: The authors aimed to gather data from the current literature on brain insulin resistance (BIR) and its likely repercussions on neurodegenerative disorders, more specifically AD, through a systematic review. Methods: A comprehensive search was conducted in multiple medical databases, including the Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline), and PubMed®, employing the descriptors: "insulin resistance", "brain insulin resistance", "Alzheimer's disease", "neurodegeneration", and "cognition". The authors focused their search on English-language studies published between 2000 and 2023 that investigated the influence of BIR on neurodegenerative disorders or offered insights into BIR's underlying mechanisms. Seventeen studies that met the inclusion criteria were selected. Results: The results indicate that BIR is a phenomenon observed in a variety of neurodegenerative disorders, including AD. Studies suggest that impaired glucose utilization and uptake, reduced adenosine triphosphate (ATP) production, and synaptic plasticity changes caused by BIR are linked to cognitive problems. However, conflicting results were observed regarding the association between AD and BIR, with some studies suggesting no association. Conclusion: Based on the evaluated studies, it can be concluded that the association between AD and BIR remains inconclusive, and additional research is needed to elucidate this relationship.

RESUMO. A incapacidade das células de reagir à insulina, ocasionando intolerância à glicose e hiperglicemia, é chamada de resistência à insulina. Essa condição clínica, que tem sido bem pesquisada em órgãos como tecido adiposo, músculo e fígado, tem sido associada às doenças neurodegenerativas como a doença de Alzheimer (DA) quando ocorre no cérebro. Objetivo: O objetivo dos autores foi reunir os dados da literatura atual sobre a resistência insulínica cerebral (RIC) e sua provável repercussão em doenças neurodegenerativas, mais especificamente na DA, por meio de uma revisão sistemática da literatura. Métodos: Foi realizada uma pesquisa abrangente em vários bancos de dados médicos, incluindo o Cochrane Central Register of Controlled Trials, EMBASE, Medical Literature Analysis and Retrieval System Online (Medline) e PubMed, empregando os descritores: "resistência à insulina", "resistência insulínica cerebral", "doença de Alzheimer", "neurodegeneração" e "cognição". Os autores concentraram sua busca em estudos no idioma inglês publicados entre 2000 e 2023 que investigaram a influência da RIC em distúrbios neurodegenerativos ou ofereceram insights sobre os mecanismos subjacentes da RIC. Dezessete estudos que atenderam aos critérios de inclusão foram selecionados. Resultados: Os resultados demonstram que a RIC é um fenômeno observado em uma variedade de doenças neurodegenerativas, incluindo a DA. Estudos sugerem que a utilização e captação prejudicadas de glicose, a produção reduzida de trifosfato de adenosina (ATP) e as alterações na plasticidade sinápticas causadas pela RIC estão ligadas a problemas cognitivos. No entanto, foram observados resultados conflitantes com relação à associação entre DA e RIC, com alguns estudos sugerindo nenhuma associação. Conclusão: Com base nos estudos avaliados, pode-se concluir que a associação entre DA e RIC ainda é inconclusiva, e pesquisas adicionais são necessárias para elucidar essa relação.

Adherencia al automonitoreo en diabetes tipo 2: plataforma "ClouDi" vs. Educación presencial. / Adherence to self-monitoring in type 2 diabetes: "ClouDi" platform vs. Face-to-face follow-up / Adesão à automonitorização na diabetes tipo 2: plataforma "ClouDi" vs. acompanha-mento presencial

Introducción: El uso de mHealth puede mejorar la adherencia a el automonitoreo con glucometría capilar (GC) en la transición del ámbito hospitalario al ambulatorio. Objetivo: evaluar la adherencia al automonitoreo con GC de los pacientes con Diabetes Tipo 2 (DM2) vinculados a un programa de educación usuarios de mHealth (ClouDi) comparado con el programa de educación y seguimiento presencial usual. Materiales y métodos: Estudio longitudinal prospectivo. Se analizaron pacientes con DM2 valorados por consulta de educación de diabetes con indicación de tratamiento con insulina al egreso hospitalario. Se analizaron dos grupos: uno con seguimiento presencial y otro vinculado a un programa educativo y uso de ClouDi. Resultados: De los 86 pacientes (44% de sexo femenino, 41 usuarios ClouDi, edad promedio 58.8 ± 11.2 años, con una media de duración de la diabetes de 7.8 ± 7.4 años), 53.6% se encontraban en estrato 2, el 92.9% pertenecían al régimen contributivo, el 42.9% con educación básica primaria y 51.2% empleados. Fue considerada la adherencia a la GC al realizar y registrar 3 o más mediciones por día en los pacientes de ClouDi fue mayor comparado con los pacientes en cuidado usual (64.4% vs 28.2%, p <0.001), independiente de las variables sociodemográficas. Conclusión: El uso de ClouDi se asoció a mayor adherencia a automonitoreo con GC comparado con seguimiento presencial independiente de variables sociodemográficas. El uso de esta tecnología podría ser útil en el seguimiento de pacientes usuarios de insulina al egreso hospitalario

Introduction: The use of mHealth can improve adherence to self-monitoring blood Glucose (SMBG) in the transition from hospital to outpatient setting. Objective: To evaluate adherence to self-monitoring with GC in patients with type 2 diabetes (T2DM) linked to an mHealth user education program (ClouDi) compared with the usual face-to-face education and follow-up program. Materials and Methods: Prospective longitudinal study. Patients with T2D assessed by diabetes education counseling with an indication for insulin treatment at hospital discharge were analyzed. Two groups were analyzed: one with face-to-face follow-up and another linked to an educational program and use of ClouDi. Results: Of the 86 patients (44% female, 41 ClouDi users, mean age 58.8 ± 11.2 years, with a mean duration of diabetes of 7.8 ± 7.4 years), 53.6% were in stratum 2, 92.9% belonged to the contributory system, 42.9% with basic pri-mary education and 51.2% were employed. Compliance with the SMBG was considered if 3 or more measurements per day were taken and recorded, was higher in ClouDi patients com-pared to usual care patients (64.4% vs. 28.2%, p <0.001), independent of sociodemographic variables.Conclusions: The use of ClouDi was associated with greater adherence to SMBG compared to in-person follow-up, independent of sociodemographic variables. The use of this technology may be useful in monitoring insulin-using patients after hospital discharge

Introdução: A utilização do mHealth pode melhorar a adesão à automonitorização com glico-metria capilar (GC) na transição do hospital para o ambulatório. Objetivo: avaliar a adesão ao automonitoramento com GC de pacientes com Diabetes Tipo 2 (DM2) vinculados a um progra-ma de educação de usuários de mHealth (ClouDi) em comparação com o programa habitual de educação e acompanhamento presencial. Materiais e métodos: Estudo prospectivo longitudi-nal. Foram analisados pacientes com DM2 avaliados por consulta de educação em diabetes com indicação de tratamento insulínico na alta hospitalar. Foram analisados dois grupos: um com acompanhamento presencial e outro vinculado a um programa educativo e uso do ClouDi. Re-sultados: Dos 86 doentes (44% do sexo feminino, 41 utilizadores do ClouDi, idade média 58,8 ± 11,2 anos, com duração média da diabetes de 7,8 ± 7,4 anos), 53,6% encontravam-se no estra-to 2, 92,9% pertenciam ao regime contributivo, 42,9% com ensino fundamental básico e 51,2% empregados. A adesão ao GC foi considerada quando realizada e registrada 3 ou mais medidas por dia em pacientes ClouDi foi maior em comparação aos pacientes em cuidados habituais (64,4% vs 28,2%, p <0,001), independente das variáveis sociodemográficas. Conclusão: O uso do ClouDi esteve associado à maior adesão ao automonitoramento com GC em comparação ao acompanhamento presencial independente das variáveis sociodemográficas. O uso dessa tecnologia pode ser útil no monitoramento de pacientes usuários de insulina na alta hospitalar

Estabilidad fisicoquímica y microbiológica de un colirio de insulina 10 UI/mL / Physicochemical and microbiological stability of a 10 IU/mL insulin eye drop

Objetivo: Los pacientes con defectos epiteliales corneales persistentes son, a menudo, refractarios a los tratamientos convencionales. La insulina tópica surge como una posible alternativa, habiendo demostrado su efectividad y seguridad. Sin embargo, en la bibliografía actual disponible, hay una falta de estudios de estabilidad. El objetivo del presente trabajo fue evaluar la estabilidad fisicoquímica y microbiológica de un colirio de insulina 10 UI/ml durante 28 días. Método: Estudio de estabilidad fisicoquímica y microbiológica. Se elaboraron 2 lotes (A y B) de colirios de insulina 10 UI/ml, manteniendo el lote B cerrado hasta el día 15. Las variables fisicoquímicas analizadas fueron la concentración de insulina mediante inmunoanálisis quimioluminiscente, pH y osmolaridad. El estudio microbiológico se realizó mediante pruebas de esterilidad mientras que el estudio descriptivo se analizó mediante visualización directa. Resultados: No se observaron cambios significativos de concentración (±10%) en los colirios a excepción de 2 valores en una de las muestras del lote B. El pH y la osmolaridad se mantuvieron dentro de los rangos fisiológicos del ojo. No se observó crecimiento microbiano ni cambios en las características organolépticas. Conclusiones: Se puede considerar al colirio de insulina 10 UI/ml estable durante 28 días en refrigeración manteniendo el frasco abierto desde el día de su elaboración.(AU)

Objective: Patients with persistent corneal epithelial defects are often refractory to conventional treatments. Topical insulin emerges as a possible alternative of proven effectiveness and safety. However, in the current available literature, there is a lack of stability studies. The main objective of this study was to evaluate the physicochemical and microbiological stability of a 10 IU/ml insulin eye drop for 28 days. Methods: Physicochemical and microbiological stability study. Two batches (A and B) of 10 IU/ml insulin eye drops were prepared, keeping batch B closed until day 15. The physicochemical variables analysed were insulin concentration by chemiluminescent immunoassay, pH and osmolarity. The microbiological study was performed by sterility tests while the descriptive study was assessed by direct visualization. Results: No significant concentration changes (±10%) were observed in the eye drops except for 2 values in one of the samples from batch B. The pH and osmolarity remained within the physiological ranges of the eye. No microbiological growth or changes in organoleptic characteristics were observed. Conclusions: Insulin 10 UI/ml eye drops can be considered stable for 28 days under refrigeration if the bottle is kept open from the day of its preparation.(AU)

Insulin eye drops for refractory corneal epithelial defects. A case series / Colirio de insulina para defectos corneales epiteliales persistentes. Una serie de casos

Objetive: To report the clinical course of a case series of patients with persistent epithelial corneal defects (PECD) treated with insulin eye drops. Method: Retrospective review of five patients -four non-diabetic and one diabetic- in treatment with insulin eye drops 1 U/mL four times a day (QID). Results: Patients developed refractory epithelial ulcers due to different etiology (three infections, one trauma and one chemical injury). After treatment with topical insulin all defects were healed in about 30-60 days. Conclusion: Insulin formulated as 1 U/mL eye drops and administered QID can be an effective and safe option for PECD. (AU)

Objetivo: Comunicar la evolución clínica de una serie de casos de pacientes con defectos corneales epiteliales persistentes (PECD) tratados con colirio de insulina. Método: Revisión retrospectiva de cinco pacientes –cuatro no diabéticos y uno diabético– en tratamiento con colirio de insulina 1 U/mL cuatro veces al día (QID). Resultados: Los pacientes desarrollaron úlceras epiteliales refractarias de diferente etiología (tres infecciones, un traumatismo y una lesión química). Tras el tratamiento con insulina tópica todos las lesiones se curaron en unos 30-60 días. Conclusión: La insulina formulada en forma de colirio de 1 U/mL y administrada QID puede ser una opción eficaz y segura para la PECD. (AU)

Serum neuregulin 1 in relation to ventricular function and subclinical atherosclerosis in type 2 diabetes patients.

BACKGROUND AND AIMS: Neuregulin 1 (NRG-1) is one of the members of the epidermal growth factors proteins. The present study provides novel insights into the relationship between serum levels of NRG-1 and insulin resistance, subclinical atherosclerosis and cardiac dysfunction that occur in type 2 diabetes (T2D). METHODS: The study included 50 patients with T2D and 40 healthy age- and gender-matched controls. Serum NRG-1 was measured using ELISA. Glycemic parameters, lipid profile and insulin resistance were assessed. Trans-thoracic echocardiography and carotid intima media thickness (CIMT) were studied for all study subjects. RESULTS: T2D patients had significantly lower serum NRG-1 levels than controls. Serum NRG-1 was negatively correlated with age, fasting blood glucose, HbA1c, insulin resistance, blood urea, serum creatinine and LDL-C, and positively correlated with HDL-C, eGFR and CIMT. Regarding echocardiographic variables, serum NRG-1 was found to correlate positively with left ventricular global longitudinal strain and negatively with E/Ea ratio. NRG-1 was found to predict subclinical atherosclerosis in type 2 diabetes patients at a cut-off value<108.5pg/ml with 78% sensitivity and 80% specificity. CONCLUSIONS: A robust relationship was found between serum NRG-1 levels and hyperglycemia, insulin resistance, subclinical atherosclerosis, and cardiac dysfunction in patients with type 2 diabetes. These results shed light on a possible role of NRG-1 as a potential noninvasive biomarker for detection of cardiometabolic risk in T2D.

[Effect of a multivitamin on insulin resistance, inflammation, and oxidative stress in a Wistar rat model of induced obesity]. / Efecto de un multivitamínico sobre la resistencia a la insulina, inflamación y estrés oxidante en un modelo de obesidad inducida en ratas Wistar.

Introduction: Introduction: excessive accumulation of adipose tissue is accompanied by alterations in the inflammatory state and increased oxidative stress, and these variables are associated with insulin resistance and increased glucose and insulin levels. On the other hand, vitamins and minerals reinforce the antioxidant and inflammatory capacity, for this reasons we propose that they could contribute to the control of insulin resistance, glucose and lipid metabolism in a rat model of obesity. Objective: to analyze the effect of a multivitamin supplement on markers of insulin resistance, inflammation, and oxidative stress in obese rats on a cafeteria diet. Methods: thirty-five 28-day-old male Wistar rats were randomly divided into four groups: 1, standard diet control; 2, standard diet plus multivitamin; 3, obese on a cafeteria diet; and 4, obese on a cafeteria diet plus multivitamin. After the treatments, glucose levels, HbA1c, insulin, TNF-α, IL-6, oxidative stress and lipid profile were analyzed by colorimetric methods, as well as the percentage of adipose tissue, Homeostasis Model Assessment (HOMA) index y Quantitative Insulin Sensitivity Check Index (QUICKI). Results: multivitamin supplementation significantly decreased visceral adipose tissue, HOMA index, glucose, HbA1c, oxidant stress, and inflammatory markers in the obese plus multivitamin rat group, compared with the obese cafeteria diet rat group and the standard diet rat control group. However, the group that was administered only the multivitamin without the cafeteria diet had increased levels of total adipose tissue, glucose, and oxidative stress, as well as the QUICKI index relative to the control group with the standard diet. Conclusion: co-administration of a multivitamin supplement may improve insulin sensitivity, glucose metabolism and lipid profile; strengthen antioxidant status; and decrease inflammation during weight gain. However, it was not expected that added sugars in multivitamin supplement can also increase total adipose tissue, oxidative stress and glucose levels, so it is suggested to use sugar-free multivitamins in the future.

Introducción: Introducción: la acumulación excesiva de tejido adiposo se acompaña de alteraciones en el estado inflamatorio y aumento del estrés oxidativo, variables que se asocian con la resistencia a la insulina e incremento en los niveles de glucosa e insulina. las vitaminas y minerales refuerzan la capacidad antioxidante e inflamatoria, por lo que planteamos que podrían coadyuvar en el control de resistencia a la insulina y en el metabolismo de la glucosa y lípidos en un modelo de obesidad en rata. Objetivo: analizar el efecto de un suplemento multivitamínico sobre marcadores de resistencia a la insulina, inflamación y estrés oxidativo en ratas obesas con dieta de cafetería. Métodos: se dividieron aleatoriamente 35 ratas macho Wistar de 28 días de edad en cuatro grupos: 1, control dieta estándar; 2, dieta estándar más multivitamínico; 3, obesas con dieta de cafetería; y 4, obesas con dieta de cafetería más multivitamínico. Después de los tratamientos se analizaron los niveles de glucosa, HbA1c, insulina, TNF-α, IL-6, estrés oxidativo y perfil de lípidos por métodos colorimétricos, así como el porcentaje de tejido adiposo y los índices Homeostasis Model Assessment (HOMA) y Quantitative Insulin Sensitivity Check Index (QUICKI). Resultados: el suplemento multivitamínico disminuyó significativamente el tejido adiposo visceral, el índice HOMA, la glucosa, la HbA1c, el estrés oxidante y los marcadores inflamatorios en el grupo obeso más multivitamínico, en comparación con el grupo obeso con dieta de cafetería y el grupo control con dieta estándar. Sin embargo, en el grupo al que se le administró solo el multivitamínico sin dieta de cafetería aumentaron sus niveles de tejido adiposo total, glucosa y estrés oxidativo, así como el índice QUICKI con relación al grupo control con dieta estándar. Conclusión: la coadministración de un suplemento multivitamínico puede mejorar la sensibilidad a la insulina, el metabolismo de glucosa y el perfil de lípidos; fortalecer el estado antioxidante; y disminuir la inflamación durante el incremento de peso. Sin embargo, no se esperaba que los azúcares añadidos en el suplemento multivitamínico también pueden incrementar el tejido adiposo total y los niveles de estrés oxidativo y glucosa, por lo que se sugiere a futuro utilizar multivitamínicos libres de azúcares.

Efecto de un multivitamínico sobre la resistencia a la insulina, inflamación y estrés oxidante en un modelo de obesidad inducida en ratas Wistar / Effect of a multivitamin on insulin resistance, inflammation, and oxidative stress in a Wistar rat model of induced obesity

Introducción: la acumulación excesiva de tejido adiposo se acompaña de alteraciones en el estado inflamatorio y aumento del estrés oxidativo, variables que se asocian con la resistencia a la insulina e incremento en los niveles de glucosa e insulina. las vitaminas y minerales refuerzan la capacidad antioxidante e inflamatoria, por lo que planteamos que podrían coadyuvar en el control de resistencia a la insulina y en el metabolismo de la glucosa y lípidos en un modelo de obesidad en rata. Objetivo: analizar el efecto de un suplemento multivitamínico sobre marcadores de resistencia a la insulina, inflamación y estrés oxidativo en ratas obesas con dieta de cafetería. Métodos: se dividieron aleatoriamente 35 ratas macho Wistar de 28 días de edad en cuatro grupos: 1, control dieta estándar; 2, dieta estándar más multivitamínico; 3, obesas con dieta de cafetería; y 4, obesas con dieta de cafetería más multivitamínico. Después de los tratamientos se analizaron los niveles de glucosa, HbA1c, insulina, TNF-α, IL-6, estrés oxidativo y perfil de lípidos por métodos colorimétricos, así como el porcentaje de tejido adiposo y los índices Homeostasis Model Assessment (HOMA) y Quantitative Insulin Sensitivity Check Index (QUICKI). Resultados: el suplemento multivitamínico disminuyó significativamente el tejido adiposo visceral, el índice HOMA, la glucosa, la HbA1c, el estrés oxidante y los marcadores inflamatorios en el grupo obeso más multivitamínico, en comparación con el grupo obeso con dieta de cafetería y el grupo control con dieta estándar. Sin embargo, en el grupo al que se le administró solo el multivitamínico sin dieta de cafetería aumentaron sus niveles de tejido adiposo total, glucosa y estrés oxidativo, así como el índice QUICKI con relación al grupo control con dieta estándar. (AU)

Introduction: excessive accumulation of adipose tissue is accompanied by alterations in the inflammatory state and increased oxidative stress, and these variables are associated with insulin resistance and increased glucose and insulin levels. On the other hand, vitamins and minerals reinforce the antioxidant and inflammatory capacity, for this reasons we propose that they could contribute to the control of insulin resistance, glucose and lipid metabolism in a rat model of obesity. Objective: to analyze the effect of a multivitamin supplement on markers of insulin resistance, inflammation, and oxidative stress in obese rats on a cafeteria diet. Methods: thirty-five 28-day-old male Wistar rats were randomly divided into four groups: 1, standard diet control; 2, standard diet plus multivitamin; 3, obese on a cafeteria diet; and 4, obese on a cafeteria diet plus multivitamin. After the treatments, glucose levels, HbA1c, insulin, TNF-α, IL-6, oxidative stress and lipid profile were analyzed by colorimetric methods, as well as the percentage of adipose tissue, Homeostasis Model Assessment (HOMA) index y Quantitative Insulin Sensitivity Check Index (QUICKI). Results: multivitamin supplementation significantly decreased visceral adipose tissue, HOMA index, glucose, HbA1c, oxidant stress, and inflammatory markers in the obese plus multivitamin rat group, compared with the obese cafeteria diet rat group and the standard diet rat control group. However, the group that was administered only the multivitamin without the cafeteria diet had increased levels of total adipose tissue, glucose, and oxidative stress, as well as the QUICKI index relative to the control group with the standard diet. (AU)

Insulina tópica en el tratamiento del defecto epitelial persistente posúlcera corneal grave

El tratamiento del defecto epitelial refractario es un reto y está sujeto al desarrollo de estudios preclínicos y clínicos con el objetivo de obtener tratamientos eficaces, entre los que emerge la insulina tópica. El objetivo del presente artículo fue describir la respuesta cicatrizal del epitelio corneal bajo tratamiento con colirio de insulina. Se presentan dos pacientes con diagnóstico de defecto epitelial persistente posúlcera corneal. Se indicó insulina tópica una gota cada 6 horas, con evolución hacia la epitelización corneal total a los 10 días de iniciado el tratamiento. Se sugiere el mecanismo por el cual la insulina promueve la cicatrización corneal al lograr la restauración de los nervios corneales y favorecer la migración de células epiteliales. En ambos casos el colirio de insulina logró la promover la cicatrización epitelial total de la córnea por lo que se es útil en el tratamiento de defecto epitelial persistente.

The treatment of refractory epithelial defect is a challenge and depends upon the development of preclinical or clinical studies aimed at obtaining effective treatments, among which topical insulin emerges. The objective of this article was to describe the healing response of the corneal epithelium under treatment with insulin eye drops. The cases are presented of two patients with a diagnosis of persistent post-corneal ulcer epithelial defect. Topical insulin was prescribed at one drop every six hours, with evolution towards total corneal epithelialization ten days after the treatment started. The mechanism is suggested by which insulin promotes corneal healing, thus restoring corneal nerves and favoring epithelial cell migration. In both cases, the insulin eye drops were able to promote total epithelial healing of the cornea, making it useful in the treatment of persistent epithelial defect.

Insulina colirio en afecciones de la superficie ocular

Cuando se produce una erosión corneal y fracasa la epitelización corneal surgen los defectos epiteliales corneales persistentes, cuyo tratamiento es un desafío para el oftalmólogo. Es muy frecuente el fracaso del tratamiento convencional por lo que se mantiene el interés en la búsqueda de otros factores de crecimiento para la cicatrización epitelial tales como los colirios de insulina. La insulina es un péptido estrechamente relacionado con el factor de crecimiento similar a la insulina 1. Su mecanismo de acción no es bien comprendido, sin embargo se acepta que es capaz de inducir migración y proliferación de las células epiteliales corneales, por lo que promueve y acelera la reepitelización de defectos epiteliales persistentes refractarios a tratamiento. La ausencia de una presentación comercial de colirio de insulina, hace necesario conocer su estabilidad físicoquímica y microbiológica así como la eficacia, efectividad y seguridad del colirio de insulina a diferentes concentraciones. De ahí la motivación para realizar una revisión de la literatura existente sobre el empleo del colirio de insulina en el tratamiento del defecto epitelial corneal persistente. Se realizó la búsqueda en bases de datos electrónicas como PubMed Central, EBSCO, Clinical Trials.gov, MEDLINE OVID, EMBASE OVID con el objeto de identificar artículos relacionados con el tema.

When corneal erosion occurs and corneal epithelialization fails, persistent corneal epithelial defects arise, whose treatment is a challenge for the ophthalmologist. The failure of conventional treatment is very frequent; therefore, there is still interest in the search for other growth factors for epithelial healing, such as insulin eye drops. Insulin is a peptide closely related to insulin-like growth factor 1. Its mechanism of action is not well understood; however, it is accepted that it is capable of inducing migration and proliferation of corneal epithelial cells, thereby promoting and accelerating reepithelialization of persistent epithelial defects refractory to treatment. The absence of a commercial presentation for insulin eye drops makes it necessary to know its physicochemical and microbiological stability, as well as the efficacy, effectiveness and safety of insulin eye drops at different concentrations; hence the motivation to review the existing literature on the use of insulin eye drops in the treatment of persistent corneal epithelial defects. The search was carried out in electronic databases such as PubMed Central, EBSCO, Clinical Trials.gov, MEDLINE OVID, EMBASE OVID, with the aim of identifying relevant articles related to the topic.

Intensive glucose control in critically ill adults: a protocol for a systematic review and individual patient data meta-analysis / Controle intensivo da glicose em adultos em estado grave: um protocolo de revisão sistemática e metanálise de dados individuais de pacientes

ABSTRACT Objective: The optimal target for blood glucose concentration in critically ill patients is unclear. We will perform a systematic review and meta-analysis with aggregated and individual patient data from randomized controlled trials, comparing intensive glucose control with liberal glucose control in critically ill adults. Data sources: MEDLINE®, Embase, the Cochrane Central Register of Clinical Trials, and clinical trials registries (World Health Organization, clinical trials.gov). The authors of eligible trials will be invited to provide individual patient data. Published trial-level data from eligible trials that are not at high risk of bias will be included in an aggregated data meta-analysis if individual patient data are not available. Methods: Inclusion criteria: randomized controlled trials that recruited adult patients, targeting a blood glucose of ≤ 120mg/dL (≤ 6.6mmol/L) compared to a higher blood glucose concentration target using intravenous insulin in both groups. Excluded studies: those with an upper limit blood glucose target in the intervention group of > 120mg/dL (> 6.6mmol/L), or where intensive glucose control was only performed in the intraoperative period, and those where loss to follow-up exceeded 10% by hospital discharge. Primary endpoint: In-hospital mortality during index hospital admission. Secondary endpoints: mortality and survival at other timepoints, duration of invasive mechanical ventilation, vasoactive agents, and renal replacement therapy. A random effect Bayesian meta-analysis and hierarchical Bayesian models for individual patient data will be used. Discussion: This systematic review with aggregate and individual patient data will address the clinical question, 'what is the best blood glucose target for critically ill patients overall?' Protocol version 0.4 - 06/26/2023 PROSPERO registration: CRD42021278869

RESUMO Objetivo: Não está claro qual é a meta ideal de concentração de glicose no sangue em pacientes em estado grave. Realizaremos uma revisão sistemática e uma metanálise com dados agregados e de pacientes individuais de estudos controlados e randomizados, comparando o controle intensivo da glicose com o controle liberal da glicose em adultos em estado grave. Fontes de dados: MEDLINE®, Embase, Cochrane Central Register of Clinical Trials e registros de ensaios clínicos (Organização Mundial da Saúde, clinical trials.gov). Os autores dos estudos qualificados serão convidados a fornecer dados individuais de pacientes. Os dados publicados em nível de ensaio qualificado que não apresentem alto risco de viés serão incluídos em uma metanálise de dados agregados se os dados individuais de pacientes não estiverem disponíveis. Métodos: Critérios de inclusão: ensaios clínicos controlados e randomizados que recrutaram pacientes adultos, com meta de glicemia ≤ 120mg/dL (≤ 6,6mmol/L) comparada a uma meta de concentração de glicemia mais alta com insulina intravenosa em ambos os grupos. Estudos excluídos: aqueles com meta de glicemia no limite superior no grupo de intervenção > 120mg/dL (> 6,6mmol/L), ou em que o controle intensivo de glicose foi realizado apenas no período intraoperatório, e aqueles em que a perda de seguimento excedeu 10% até a alta hospitalar. Desfecho primário: Mortalidade intra-hospitalar durante a admissão hospitalar. Desfechos secundários: Mortalidade e sobrevida em outros momentos, duração da ventilação mecânica invasiva, agentes vasoativos e terapia de substituição renal. Utilizaremos metanálise bayesiana de efeito randômico e modelos bayesianos hierárquicos para dados individuais de pacientes. Discussão: Essa revisão sistemática com dados agregados e de pacientes individuais abordará a questão clínica: Qual é a melhor meta de glicose no sangue de pacientes graves em geral? Protocolo versão 0.4 - 26/06/2023 Registro PROSPERO: CRD42021278869