ABSTRACT
Chronic inflammation has long been considered the characteristic feature of type II diabetes mellitus (T2DM) Immunopathogenesis. Pro-inflammatory cytokines are considered the central drivers of the inflammatory cascade leading to ß-cell dysfunction and insulin resistance (IR), two major pathologic events contributing to T2DM. Analyzing the cytokine profile of T2DM patients has also introduced interleukin-17 (IL-17) as an upstream regulator of inflammation, regarding its role in inducing the nuclear factor-kappa B (NF-κB) pathway. In diabetic tissues, IL-17 induces the expression of inflammatory cytokines and chemokines. Hence, IL-17 can deteriorate insulin signaling and ß-cell function by activating the JNK pathway and inducing infiltration of neutrophils into pancreatic islets, respectively. Additionally, higher levels of IL-17 expression in patients with diabetic complications compared to non-complicated individuals have also proposed a role for IL-17 in T2DM complications. Here, we highlight the role of IL-17 in the Immunopathogenesis of T2DM and corresponding pathways, recent advances in preclinical and clinical studies targeting IL-17 in T2DM, and corresponding challenges and possible solutions.
Subject(s)
Diabetes Mellitus, Type 2 , Interleukin-17 , Humans , Diabetes Mellitus, Type 2/immunology , Interleukin-17/immunology , Animals , Inflammation/immunology , Insulin-Secreting Cells/immunology , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/pathology , Diabetes Complications/immunology , Insulin Resistance/immunology , Signal Transduction/immunologyABSTRACT
Due to the great amount of information generated and supported by the explosive evolution of computer science systems since the end of the last century, the expansion and transference of scientific knowledge has caused a rapid transformation of scientific discoveries in products and applications that have positive effects in the life quality of societies. Today, a great amount of data in medicine is obtained by the application of biotechnological methods that constantly evolve. Thus, scientific research related to diabetes keeps improving. In this context, productivity and competitiveness must be sustained on knowledge which facilitates and encourages organizational innovation capacity. For this reason, knowledge based systems emerge as a useful tool to help organizations solve difficult assignments or improve their processes. In this work, derivate from known diabetes group of symptoms and interactions that diabetes research maintains with the biotechnological processes, the authors carried out a brief analysis of the knowledge involved as well as the role that knowledge-based systems have played, and keep playing in support of them. Additionally, with the systemic perspective obtained by the authors regarding aspects like knowledge, practices and resources needed in clinical and laboratory practices, they propose a systemic model that can support diabetes research and clinical process.
Debido a la gran cantidad de información generada y apoyada por la evolución explosiva de sistemas de la ciencia computacional, desde finales del siglo pasado, la expansión y transferencia de conocimiento científico ha provocado una rápida transformación de los descubrimientos científicos en productos y aplicaciones que afectan positivamente la calidad de vida de las sociedades. Actualmente, una gran cantidad de datos en medicina se obtiene por la aplicación de métodos biotecnológicos que constantemente evolucionan. De igual manera, la investigación científica sobre diabetes mantiene una mejora constante. En este contexto, tanto la productividad como la competitividad se deben apoyar con conocimiento que facilite y promueva la capacidad de innovación organizacional. Por esta razón, los sistemas basados en conocimiento emergen como una herramienta útil para coadyuvar con las organizaciones en la solución de situaciones difíciles o en la mejora de sus procesos. En este trabajo, derivado del conocido grupo de síntomas y de las interacciones que la investigación en diabetes mantiene con los procesos biotecnológicos, los autores realizan un breve análisis del conocimiento implicado y del rol que los sistemas basados en el conocimiento han desempeñado, -y continúan desempeñando, en apoyo a tales procesos. Adicionalmente, con la perspectiva sistémica obtenida por los autores respecto al conocimiento y recursos necesarios en prácticas clínicas y de laboratorio, proponen un modelo sistémico capaz de apoyar la investigación y el proceso clínico de la diabetes.
Subject(s)
Humans , Diabetes Complications/physiopathology , Diabetes Complications/chemically induced , Diabetes Complications/immunology , Diabetes Complications/bloodABSTRACT
La integración de metabolismo e inmunidad bajo condiciones normales es benéfica para mantener la homeostasis, pero puede ser deletérea bajo condiciones de cambio metabólico como en la inmunosupresión característica de la desnutrición. Con el incremento del sobrepeso y la obesidad, nuevos problemas de la intersección del metabolismo e inmunidad han emergido: obesidad asociada a enfermedades inflamatorias, diabetes, hígado graso y aterosclerosis. Existe un alto nivel de coordinación entre las vías metabólica e inflamatoria y destacan en este sentido los macrófagos y los adipocitos en la obesidad. Las señales intracelulares activadas en la respuesta a la inflamación pueden inhibir la señal de la insulina. La pérdida de mediadores o moléculas de señalización inflamatorios previene la resistencia a la insulina. En ausencia de obesidad, una infusión de citocinas inflamatorias o lípidos causa resistencia a la insulina. Entender los mecanismos que conducen de obesidad a inflamación tendrá importantes implicaciones para reducir la morbilidad y mortalidad de la obesidad a través de prevenir su asociación con inflamación.
Integration of metabolism and immunity in normal physiology is beneficial to maintain homeostasis. It can also become deleterious under conditions such as the immunosuppression observed among the malnourished. With the increase of excess weight and obesity, a new set of problems and complications has emerged at the intersection of metabolic activity and immunity. As examples of the latter we find obesity associated with inflammatory diseases, diabetes, fatty liver disease and atherosclerosis. Obesity is characterized by inflammation; there are common factors at the crossroads of inflammation and metabolic disease. Obesity is characterized by an inflammatory response and many inflammatory mediators exhibit expression patterns that interfere with insulin action. The high level of coordination of inflammatory and metabolic pathways is highlighted by the overlapping biology of macrophage and adipocite function observed in obesity. The intracellular signaling pathways activated by inflammatory and stress responses inhibit insulin signaling and the loss of inflammatory mediators prevents insulin resistance. In the absence of obesity, an infusion of inflammatory cytokines or lipids causes insulin resistance. Understanding the mechanisms leading from obesity to inflammation will have important implications to help reduce the morbidity and mortality associated with obesity by preventing its association with inflammatory disorders.
Subject(s)
Humans , Diabetes Complications/complications , Inflammation/complications , Obesity/complications , Diabetes Complications/immunology , Diabetes Complications/metabolism , Insulin Resistance , Inflammation/immunology , Inflammation/metabolism , Obesity/immunology , Obesity/metabolismABSTRACT
OBJETIVO: Revisão sistemática do conhecimento atual sobre a associação entre diabetes melito (DM) e doença periodontal (DP) com ênfase na sua fisiopatogenia. FONTE DE DADOS: Pesquisa bibliográfica, nos últimos cinco anos, através dos bancos de dados MEDLINE e LILACS, usando as palavras-chaves "diabetes mellitus", "periodontal disease" e "periodontitis". SÍNTESE DOS DADOS: Os tecidos periodontais são as estruturas bucais mais afetadas pelo DM. O DM predispõe ao desenvolvimento da DP, a qual leva ao descontrole glicêmico, o que ressalta a importância da relação bidirecional entre essas duas doenças. Vários mecanismos estão envolvidos na fisiopatologia da DP associada ao DM: produção de produtos de glicosilação avançada, deficiente resposta imune, herança de determinados polimorfismos genéticos, alterações dos vasos sanguíneos, tecido conjuntivo e composição salivar. Na fase inicial predominam a gengivite e periodontite. Se não detectados precocemente, esses problemas podem evoluir para doença periodontal avançada. Puberdade, maior duração da doença, mau controle metabólico e higiene bucal inadequada são fatores que contribuem para progressão e agressividade da DP. CONCLUSÃO: O melhor conhecimento dos mecanismos envolvidos na fisiopatogenia da DP associada ao DM auxiliará na instituição de medidas preventivas e terapêuticas precoces. É importante que médicos e dentistas orientem os pacientes com DM sobre a necessidade de bom controle glicêmico e higiene bucal adequada para minimizar os riscos de doença periodontal.
OBJETIVE: Systematic review of present knowledge about the association between diabetes mellitus (DM) and periodontal disease (PD) with emphasis on their physiopathogenesis. DATA SOURCES: Bibliographic search through MEDLINE and LILACS databases, in the last five years, using the following descriptors: "diabetes mellitus", "periodontal disease", and "periodontitis". SUMMARY OF DATA: Periodontal tissues are the oral structures most affected by DM. DM predisposes to the development of PD, which leads to loss of glycemic control, which emphasizes the importance of the two-way relationship between these two diseases. Several mechanisms are involved in the physiopathology of PD associated with DM: production of advanced glycosilation products, deficient immune response, inheritance of certain genetic polymorphisms, alterations in blood vessels, conjunctive tissue and salivary composition. In the initial phase, gingivitis and periodontitis predominate. If not detected early, these problems can develop into advanced periodontal disease. Puberty, with its hormonal alterations, longer duration of the disease, poor metabolic control and inadequate oral hygiene are factors that contribute to PD progression and aggressiveness. CONCLUSION: Better knowledge about the mechanisms involved in the physiopathogenesis of PD associated with DM would help to institute early preventive and therapeutic measures. It is important for doctors and dentists to instruct their patients with DM about the need for good glycemic control and adequate oral hygiene, to minimize the risks for the appearance of periodontal disease and consequent loss of glycemic control.
Subject(s)
Humans , Diabetes Complications , Periodontal Diseases/etiology , Cytokines/metabolism , Disease Progression , Diabetes Complications/immunology , Diabetes Complications/metabolism , Gingivitis/complications , Inflammation Mediators/metabolism , Oral Hygiene , Periodontal Diseases/immunology , Periodontal Diseases/metabolism , Periodontal Diseases/prevention & control , Periodontitis/complications , Receptors, Immunologic/metabolism , SalivaABSTRACT
Para avaliar a resposta inflamatória, representada pelas proteínas de fase aguda, estudamos 48 pacientes com diabetes tipo 1 (DM1) sem complicações [23F:25M; 19,9±9,8 anos e 5 (1-21) anos de duração da doença& e 66 indivíduos sem DM, pareados quanto ao sexo, idade e estadiamento puberal (critérios de Tanner). Foram dosadas proteína C reativa (PCR), alfa1-glicoproteína ácida (alfa-1GPA) e fibrinogênio, por imuno-turbidimetria. A taxa de excreção de albumina (EUA) foi determinada por RIE, em amostra de urina de 10h, definindo-se normoalbuminúria como duas taxas de EUA <20µg/min. Pacientes com DM1 foram avaliados quanto à presença de retinopatia por oftalmoscopia indireta. No DM1 os níveis de PCR [0,23 (0,01-2,90) vs. 0,14 (0,01-2,41) mg/dl, p= 0,0172& e de alfa1-GPA [53,5 (37-115) vs. 40 (19-78) mg/dl, p< 0,0001& foram maiores quando comparados aos sem DM. Não houve diferença em relação ao fibrinogênio. Na regressão linear múltipla em stepwise, tendo a a1-GPA como variável dependente, as variáveis independentes associadas e preditoras foram a HbA1c (r²= 0,26; p< 0,05) e a glicemia (r²= 0,26; p< 0,05); tendo a PCR e o fibrinogênio como variáveis dependentes, nenhuma variável independente foi significativa. Na correlação de Pearson, a PCR correlacionou-se com HbA1c (r= 0,18; p= 0,05). Concluímos que a PCR e alfa1-GPA estão aumentadas no DM1, independente da presença da microalbuminúria, retinopatia e doença macrovascular clínica. Estudo prospectivo será necessário para estabelecermos o valor preditivo destes marcadores na evolução para complicações crônicas micro e macrovasculares.