Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.857
Filtrar
1.
Lima; Instituto Nacional de Salud; sept. 2020.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-1122251

RESUMO

INTRODUCCIÓN: Este documento técnico se realiza a solicitud de la Dirección de Prevención y Control de Enfermedades No Transmisibles, Raras y Huérfanas del Ministerio de Salud; la cual motivó la realización de la pregunta PICO por parte de médicos y especialistas de la siguiente manera, P: pacientes con diagnóstico de diabetes mellitus tipo 1 (DM1); I: análogos de insulina humana; C: insulina humana; O: control glucémico, calidad de vida y eventos adversos. A. Cuadro clínico La DM1 es una forma de enfermedad autoinmune que ocasiona la destrucción de las células que producen insulina. En el Perú, para el 2018, los casos de DM1 representaron el 2,7% del total de casos de diabetes. El uso de insulina representa el pilar de tratamiento farmacológico de las personas con DM1, permitiendo alcanzar un adecuado control glicémico y disminuir las complicaciones macro y microvasculares. En la actualidad, además de la insulina humana recombinante, existen en el mercado nuevas formulaciones denominados análogos de insulina humana, desarrollados con el propósito de imitar de forma más precisa el comportamiento de la insulina fisiológica. B. Tecnología sanitaria Los análogos de insulina son un tipo de insulinas cuyas moléculas han sido modificadas en la secuencia de aminoácidos. Existen tres tipos principales: de acción rápida (aspart, lispro, glulisina), de acción prolongada (glargina, detemir, degludec) y las formulaciones de análogos de insulina premezclados. Los análogos de insulina permiten emular más estrechamente la fisiología normal de la insulina y seleccionar diferentes regímenes según las preferencias y estilo de vida del paciente. Sin embargo, su precio es significativamente más alto que la insulina humana. En Perú, los análogos de insulina humana cuentan con un total de doce registros sanitarios vigentes. OBJETIVO: Describir la evidencia científica disponible sobre la eficacia y seguridad del uso de análogos de insulina humana para el control glicémico de pacientes con diabetes tipo 1. METODOLOGÍA: Se realizó una búsqueda en Medline, Cochrane Database of Systematic Reviews, CENTRAL, EMBASE y LILACS hasta el 01 de setiembre de 2020, complementada con la búsqueda de evidencia en páginas institucionales de agencias gubernamentales y buscadores genéricos. La calidad de la evidencia se valoró usando: AMSTAR 2 para RS y AGREE II para valorar el rigor metodológico de las GPC. RESULTADOS: Se identificó cinco revisiones sistemáticas, siete guías de práctica clínica y cinco evaluaciones de tecnología sanitaria. CONCLUSIONES: En adultos con DM1, los análogos de insulina de acción rápida redujeron en promedio la glucosa postprandial en 19 mg/dL, la hemoglobina glicosilada en 0,13% y el riesgo de hipoglicemia general, nocturna y severa (en 7%, 45% y 32%, respectivamente) comparado con insulina humana. En población pediátrica, no se observó una reducción en los niveles de hemoglobina glicosilada, ni en el riesgo de episodios de hipoglicemia. En ambas poblaciones, el impacto sobre la calidad de vida fue inconsistente. En adultos con DM1, los análogos de insulina de acción lenta redujeron en promedio la hemoglobina glicosilada en 0,17% y el riesgo de hipoglicemia general y nocturna (en 7% y 32%, respectivamente), sin diferencias en el riesgo de hipoglicemia severa. El impacto sobre la calidad de vida fue inconsistente. Las seis GPC incluyen en sus recomendaciones el uso de análogos de insulina e insulina humana para pacientes pediátricos o adultos con DM1. En tres de ellas, se recomienda preferentemente usar análogos de insulina, mientras en otras tres no se establece algún tipo de preferencia entre el uso de ambas formulaciones. Cinco informes de ETS, procedentes de agencias de Canadá, España y Perú, coinciden en no recomendar el uso de análogos de insulina debido a insuficiente evidencia sobre su beneficio clínico y aspectos relacionados con su costo-efectividad. Dos RS fueron consideradas como nivel de confianza críticamente bajo, mientras que tres RS fueron consideradas como nivel de confianza alto. Las GPC incluidas obtuvieron un puntaje global promedio en la evaluación de calidad que varió entre 69,4% y 80,4%.


Assuntos
Humanos , Diabetes Mellitus Tipo 1/prevenção & controle , Insulina Regular Humana/análogos & derivados , Peru , Avaliação da Tecnologia Biomédica , Análise Custo-Benefício
2.
Adv Exp Med Biol ; 1228: 107-121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32342453

RESUMO

Diabetes mellitus (DM) is the most common endocrine and metabolic disease caused by absolute or insufficient insulin secretion. Under the context of an aging population worldwide, the number of diabetic patients is increasing year by year. Most patients with diabetes have multiple complications that severely threaten their survival and living quality. DM is mainly divided into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). T1DM is caused by absolute lack of insulin secretion, so the current treatment for T1DM patients is exogenous insulin replacement therapy. At present, exercise therapy has been widely recognized in the prevention and treatment of diabetes, and regular aerobic exercise has become an important part of T1DM treatment. At the same time, exercise therapy is also used in conjunction with other treatments in the prevention and treatment of diabetic complications. However, for patients with T1DM, exercise still has the risk of hypoglycemia or hyperglycemia. T1DM Patients and specialist physician need to fully understand the effects of exercise on metabolism and implement individualized exercise programs. This chapter reviews the related content of exercise and T1DM.


Assuntos
Diabetes Mellitus Tipo 1 , Exercício Físico , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 1/terapia , Humanos , Insulina/metabolismo
3.
Nat Commun ; 11(1): 1922, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321922

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing pancreatic ß-cells are destroyed. Intestinal helminths can cause asymptomatic chronic and immunosuppressive infections and suppress disease in rodent models of T1D. However, the underlying regulatory mechanisms for this protection are unclear. Here, we report that CD8+ regulatory T (Treg) cells prevent the onset of streptozotocin -induced diabetes by a rodent intestinal nematode. Trehalose derived from nematodes affects the intestinal microbiota and increases the abundance of Ruminococcus spp., resulting in the induction of CD8+ Treg cells. Furthermore, trehalose has therapeutic effects on both streptozotocin-induced diabetes and in the NOD mouse model of T1D. In addition, compared with healthy volunteers, patients with T1D have fewer CD8+ Treg cells, and the abundance of intestinal Ruminococcus positively correlates with the number of CD8+ Treg cells in humans.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Tipo 1/imunologia , Células Secretoras de Insulina/imunologia , Linfócitos T Reguladores/imunologia , Animais , Clostridiales , Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 1/prevenção & controle , Modelos Animais de Doenças , Faecalibacterium prausnitzii , Feminino , Microbioma Gastrointestinal , Humanos , Imunossupressores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , RNA Ribossômico 16S/metabolismo , Ruminococcus , Trealose/farmacologia
4.
Sci Rep ; 10(1): 6156, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32273533

RESUMO

Antigen (Ag)-specific tolerization prevents type 1 diabetes (T1D) in non-obese diabetic (NOD) mice but proved less effective in humans. Several auto-Ags are fundamental to disease development, suggesting T1D etiology is heterogeneous and may limit the effectiveness of Ag-specific therapies to distinct disease endotypes. Colonization factor antigen I (CFA/I) fimbriae from Escherichia coli can inhibit autoimmune diseases in murine models by inducing bystander tolerance. To test if Ag-independent stimulation of regulatory T cells (Tregs) can prevent T1D onset, groups of NOD mice were orally treated with Lactococcus lactis (LL) expressing CFA/I. LL-CFA/I treatment beginning at 6 weeks of age reduced disease incidence by 50% (p < 0.05) and increased splenic Tregs producing both IL-10 and IFN-γ 8-fold (p < 0.005) compared to LL-vehicle treated controls. To further describe the role of these Tregs in preventing T1D, protective phenotypes were examined at different time-points. LL-CFA/I treatment suppressed splenic TNF-α+CD8+ T cells 6-fold at 11 weeks (p < 0.005) and promoted a distinct microbiome. At 17 weeks, IFN-γ+CD4+ T cells were suppressed 10-fold (p < 0.005), and at 30 weeks, pancreatic Tbet+CD4+ T cells were suppressed (p < 0.05). These results show oral delivery of modified commensal organisms, such as LL-CFA/I, may be harnessed to restrict Th1 cell-mediated immunity and protect against T1D.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Proteínas de Fímbrias/uso terapêutico , Administração Oral , Animais , Modelos Animais de Doenças , Feminino , Proteínas de Fímbrias/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos NOD , Linfócitos T Reguladores/fisiologia
5.
Enferm. clín. (Ed. impr.) ; 30(2): 82-88, mar.-abr. 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-193275

RESUMO

Objetivo: Evaluar la efectividad clínica y la rentabilidad del sistema de monitorización flash con FreeStyle Libre(R) versus la monitorización tradicional en pacientes con diabetes mellitus tipo 1 en el Área de Salud de Burgos (España) por medio de la comparación del gasto en recursos materiales utilizados para la monitorización de la glucemia antes y después de la utilización de este sistema. Método: Se realiza un estudio descriptivo transversal, ambispectivo, para comparar los costes y la efectividad entre dos formas de control de glucemia. La información se obtiene de la historia clínica informatizada (Medora) y por referencia del paciente; se analiza un año pre- y un año pos-FreeStyle Libre(R) el material para la monitorización y las variables clínicas de control glucémico (HbA1c y eventos de hipoglucemia [< 70 mg/dl] sintomática). Resultados: Se incluyen 23 pacientes con diabetes mellitus tipo 1 de 35,4 (± 15,1) años de edad (60,9% varones). La monitorización por el sistema FreeStyle Libre(R) tiene un coste anual medio por paciente 4 veces mayor que el método tradicional. El nivel de HbA1c se reduce un 5% (p = 0,024) y la tasa de hipoglucemias sintomáticas baja un 58,9% (p = 0,013). Esto determina una efectividad en la reducción absoluta de riesgo de 0,232 (23,2%) a nivel de hipoglucemias y un coste-efectividad incremental de 6.194,71 €. Conclusiones: El sistema FreeStyle Libre(R) presenta una efectividad clínica elevada asociada a un coste alto potencialmente aceptable para la monitorización de la glucemia en la diabetes mellitus tipo 1


Objective: This study seeks to evaluate the clinical effectiveness and cost-effectiveness of FreeStyle Libre (R) versus traditional monitoring in patients with type 1 diabetes mellitus in the Health Area of Burgos (Spain). Method: A transversal ambispective descriptive study was carried out to compare costs and effectiveness between two forms of glycaemic control. The information was obtained from the computerized clinical history (Medora) and by referring to patients. An analysis of the monitoring material and clinical glycaemic control variables (HbA1c and symptomatic hypoglycaemia events, < 70 mg/dL) were carried out one year before and one year after the start of FreeStyle Libre(R). Results: We included 23 patients with type 1 diabetes mellitus of 35.4 (± 15.1) years old (60.9% males). Monitoring by FreeStyle Libre(R) system has an average annual cost per patient four times higher than the traditional method. The HbA1c level was reduced by 5% (P= .024) and the rate of symptomatic hypoglycaemia decreased by 58.9% (P = .013). This determines an effectiveness in the absolute risk reduction of .232 (23.2%) of hypoglycaemia and an incremental cost-effectiveness of € 6,194.71. Conclusions: The FreeStyle Libre(R) system has a high clinical effectiveness associated with a high but potentially acceptable cost for glycaemia monitoring in type 1 diabetes mellitus


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Análise Custo-Benefício , Automonitorização da Glicemia/economia , Diabetes Mellitus Tipo 1/prevenção & controle , Atenção Primária à Saúde
6.
Diabetes ; 69(5): 965-980, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32169893

RESUMO

As an alternative to lifelong insulin supplementation, potentiation of immune tolerance in patients with type 1 diabetes could prevent the autoimmune destruction of pancreatic islet ß-cells. This study was aimed to assess whether the G3c monoclonal antibody (mAb), which triggers the glucocorticoid-induced TNFR-related (Gitr) costimulatory receptor, promotes the expansion of regulatory T cells (Tregs) in SV129 (wild-type) and diabetic-prone NOD mice. The delivery of the G3c mAb via G3C hybridoma cells enveloped in alginate-based microcapsules (G3C/cps) for 3 weeks induced Foxp3+ Treg-cell expansion in the spleen of wild-type mice but not in Gitr-/- mice. G3C/cps also induced the expansion of nonconventional Cd4+Cd25-/lowFoxp3lowGitrint/high (GITR single-positive [sp]) Tregs. Both Cd4+Cd25+GitrhighFoxp3+ and GITRsp Tregs (including also antigen-specific cells) were expanded in the spleen and pancreas of G3C/cps-treated NOD mice, and the number of intact islets was higher in G3C/cps-treated than in empty cps-treated and untreated animals. Consequently, all but two G3C/cps-treated mice did not develop diabetes and all but one survived until the end of the 24-week study. In conclusion, long-term Gitr triggering induces Treg expansion, thereby delaying/preventing diabetes development in NOD mice. This therapeutic approach may have promising clinical potential for the treatment of inflammatory and autoimmune diseases.


Assuntos
Anticorpos Monoclonais , Encapsulamento de Células , Diabetes Mellitus Tipo 1/prevenção & controle , Proteína Relacionada a TNFR Induzida por Glucocorticoide/metabolismo , Hibridomas , Linfócitos T Reguladores/fisiologia , Animais , Proliferação de Células , Ensaio de Imunoadsorção Enzimática , Feminino , Regulação da Expressão Gênica , Proteína Relacionada a TNFR Induzida por Glucocorticoide/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout
7.
Curr Diabetes Rev ; 16(5): 438-441, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31584373

RESUMO

Type 1 diabetes mellitus (T1DM), an autoimmune disorder, is becoming widespread with approximately 97,700 children in India and 490,000 children worldwide affected. There are various etiological factors contributing to the expansion of its incidence on different geographical locations. Hence, the articles published in reputed journals were studies and data were collected for analyzing the etiology and prevention of T1DM. It has been observed that hybrid insulin peptides act as key antigens for the autoreactive T cells and cause the loss of self-tolerance in humans. The association of coxsackievirus B has been observed with the onset of T1DM. Accurate identification of the trigger can lead to the development of appropriate preventive measures. It can become a base for advance studies to prevent T1DM in humans. This review will highlight the causes and some preventive actions which can be considered to eliminate T1DM.


Assuntos
Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/prevenção & controle , Criança , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Humanos , Incidência , Índia/epidemiologia , Insulina/imunologia
8.
Behav Sleep Med ; 18(5): 622-636, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31370700

RESUMO

BACKGROUND: Type 1 diabetes mellitus (T1DM) is a common chronic illness of childhood, with parents assuming considerable responsibility for night-time diabetes caregiving. This qualitative study explored diabetes-related factors affecting, and solutions proposed to improve, parental sleep. PARTICIPANTS: 10 mothers and 10 fathers of children ≤18 years of age with T1DM in Otago, New Zealand. METHODS: Semi-structured individual interviews were audio-recorded, transcribed, and systematically coded for themes. Parents completed the Pittsburgh Sleep Quality Index (PSQI) and habitual sleep of parents and children were assessed via 7-day actigraphy. RESULTS: Parents (n = 20) and their children with T1DM (n = 16) were aged between 32 and 54 years, and 1 and 17 years, respectively. PSQI revealed poor quality sleep in 13/20 parents. A range of diabetes-related factors, including glucose monitoring and fear of hypoglycemia, contributed to parental sleep disturbance, including awakenings and the perception of "sleeping lightly". Two distinct time periods resulted in greater sleep disturbance, notably, following T1DM diagnosis and when transitioning to using a new diabetes technology. Factors influencing maternal and paternal sleep were similar, but, generally, mothers described greater night-time care burden and sleep disturbance. While the use of diabetes technologies was generally advocated to improve parental sleep and the provision of nocturnal T1DM care, they were also perceived to potentially contribute to parental sleep disturbance. CONCLUSIONS: Pediatric diabetes care teams should be aware of diabetes-related factors potentially affecting parental sleep, the mixed impacts of diabetes technologies, and consider tailored parental support and education to reduce the burden of nocturnal care.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 1/terapia , Transtornos do Sono-Vigília/etiologia , Adolescente , Adulto , Cuidadores , Criança , Pré-Escolar , Estudos de Avaliação como Assunto , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pais , Pesquisa Qualitativa
9.
Eur J Pharmacol ; 866: 172801, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31738935

RESUMO

Ginseng has been traditionally used to treat diabetes mellitus (DM) in China. Ginsenoside Rg1 is a major active ingredient in processed ginseng, which elicits proven biological and pharmacological effects. Although a correlation between nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and predisposition to type 1 diabetes mellitus (T1DM) has been identified, the mechanism underlying the potential function and activation of NLRP3 inflammasome in DM have not been elucidated to date. The present study aimed to elucidate the effects and underlying mechanism of Rg1 on streptozotocin (STZ)-induced T1DM in mice through short or long-term observation. Concurrently, we intended to explore the relationships between inflammasome, pyroptosis and oxidative stress and the role of NLRP3 and Keap1/Nrf2/HO-1 pathways in the development and progression of DM. Using ELISA and Western blot analysis, we found that Rg1 attenuated abnormally elevated blood glucose, reduced inflammatory factors IL-1ß and IL-18 in the blood, decreased ALT and AST levels, promoted insulin secretion, and weakened the function of NLRP3 in mouse liver and pancreas. In addition, Rg1 protected against STZ-induced reactive oxygen species-mediated inflammation by upregulating Nrf2/ARE pathway, which further activated antioxidant enzymes. Interestingly, Rg1 also regulated H3K9 methylation in liver and pancreas, as detected by immunohistochemistry. In summary, these data provide new understanding about the mechanism of Rg1 action, suggesting that it is a potential drug applied for preventing the occurrence and development of T1DM.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/prevenção & controle , Ginsenosídeos/farmacologia , Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/patologia , Histonas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metilação/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/farmacologia
12.
Sci Rep ; 9(1): 19350, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852918

RESUMO

TLR4 is a transmembrane receptor of the innate immune system that recognizes LPS from gram-negative bacteria. Its stimulation induces pro-inflammatory responses and modulates adaptive immunity. Our aim is to determine the role of TLR4 in the activation and proliferation of T lymphocytes in the onset of autoimmune diabetes, using the non-obese diabetic (NOD) mouse model. Antigen-specific activation and proliferation of diabetogenic T cells were assessed in vitro by Carboxyfluorescein succinimidyl ester (CFSE) dilution, in presence of vehicle or CLI-095, a cyclohexene derivative that inhibits TLR4 signaling. NOD mice were treated with vehicle or CLI-095 and sacrificed either before or after the onset of autoimmune diabetes. T lymphocyte activation and proliferation were evaluated in treated and control mice. Insulitis was analyzed by histology and diabetes incidence was determined in treated and control mice. Our results demonstrate that TLR4 blockade decreases CD4+ T lymphocyte activation and auto-antigen-specific proliferation both in vitro and in vivo, decreases the infiltrative insulitis and finally prevents the onset of spontaneous diabetes. Taken together, our data demonstrate that TLR4 signaling contributes to the development and maintenance of autoimmune diabetes. The immunomodulatory effect of CLI-095 could be part of a preventive strategy targeting patients at risk for type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Receptor 4 Toll-Like/antagonistas & inibidores , Transferência Adotiva , Animais , Complexo CD3/metabolismo , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Proliferação de Células/efeitos dos fármacos , Epitopos/metabolismo , Feminino , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Camundongos Endogâmicos NOD , Receptores de Antígenos de Linfócitos T/metabolismo , Sulfonamidas/farmacologia , Receptor 4 Toll-Like/metabolismo
13.
J Med Internet Res ; 21(12): e15401, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31815677

RESUMO

BACKGROUND: In recent years, the rapid development of mobile medical technology has provided multiple ways for the long-term management of chronic diseases, especially diabetes. As a new type of management model, smartphone apps are global, convenient, cheap, and interactive. Although apps were proved to be more effective at glycemic control, compared with traditional computer- and Web-based telemedicine technologies, how to gain a further and sustained improvement is still being explored. OBJECTIVE: The objective of this study was to investigate the effectiveness of an app-based interactive management model by a professional health care team on glycemic control in Chinese patients with poorly controlled diabetes. METHODS: This study was a 6-month long, single-center, prospective randomized controlled trial. A total of 276 type 1 or type 2 diabetes patients were enrolled and randomized to the control group (group A), app self-management group (group B), and app interactive management group (group C) in a 1:1:1 ratio. The primary outcome was the change in glycated hemoglobin (HbA1c) level. Missing data were handled by multiple imputation. RESULTS: At months 3 and 6, all 3 groups showed significant decreases in HbA1c levels (all P<.05). Patients in the app interactive management group had a significantly lower HbA1clevel than those in the app self-management group at 6 months (P=.04). The average HbA1c reduction in the app interactive management group was larger than that in the app self-management and control groups at both months 3 and 6 (all P<.05). However, no differences in HbA1c reduction were observed between the app self-management and control groups at both months 3 and 6 (both P>.05). Multivariate line regression analyses also showed that the app interactive management group was associated with the larger reduction of HbA1c compared with groups A and B at both months 3 and 6 (all P>.05). In addition, the app interactive management group had better control of triglyceride and high-density lipoprotein cholesterol levels at both months 3 and 6 compared with baseline (both P<.05). CONCLUSIONS: In Chinese patients with poorly controlled diabetes, it was difficult to achieve long-term effective glucose improvement by using app self-management alone, but combining it with interactive management can help achieve rapid and sustained glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02589730; https://clinicaltrials.gov/ct2/show/NCT02589730.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Autogestão , Smartphone , Telemedicina , Grupo com Ancestrais do Continente Asiático , Glicemia , China , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Software , Resultado do Tratamento
14.
J Diabetes Res ; 2019: 9430473, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781669

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic ß cells by autoantigen-reactive diabetogenic cells. Antigen-specific therapies using islet autoantigens for restoring immune tolerance have emerged as promising approaches for the treatment of T1D but have been unsuccessful in humans. Herein, we report that RGI-3100-iB, a novel liposomal formulation carrying both α-galactosylceramide (α-GalCer), which is a representative ligand for invariant natural killer T (iNKT) cells, and insulin B chain 9-23 peptide, which is an epitope for CD4+ T cells, could induce the accumulation of regulatory T cells (Tregs) in islets in a peptide-dependent manner, followed by the remarkable prevention of diabetes onset in nonobese diabetic (NOD) mice. While multiple administrations of a monotherapy using either α-GalCer or insulin B peptide in a liposomal formulation was confirmed to delay/prevent T1D in NOD mice, RGI-3100-iB synergistically enhanced the prevention effect of each monotherapy and alleviated insulitis in NOD mice. Immunopathological analysis showed that Foxp3+ Tregs accumulated in the islets in RGI-3100-iB-treated mice. Cotransfer of diabetogenic T cells and splenocytes of NOD mice treated with RGI-3100-iB, but not liposomal α-GalCer encapsulating an unrelated peptide, to NOD-SCID mice resulted in the prevention of diabetes and elevation of Foxp3 mRNA expression in the islets. These data indicate that the migration of insulin B-peptide-specific Tregs to islet of NOD mice that are involved in the suppression of pathogenic T cells related to diabetes onset and progression could be enhanced by the administration of liposomes containing α-GalCer and insulin B peptide.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Galactosilceramidas/administração & dosagem , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Ilhotas Pancreáticas/efeitos dos fármacos , Células T Matadoras Naturais/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Linfócitos T Reguladores/efeitos dos fármacos , Transferência Adotiva , Animais , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Modelos Animais de Doenças , Composição de Medicamentos , Feminino , Fatores de Transcrição Forkhead/metabolismo , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/metabolismo , Lipossomos , Camundongos Endogâmicos NOD , Camundongos SCID , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/transplante
15.
Int J Mol Sci ; 20(21)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731478

RESUMO

Intracellular calcium ion content is tightly regulated for the maintenance of cellular functions and cell survival. Calbindin-D9k (CaBP-9k) is responsible for regulating the distribution of cytosolic free-calcium ions. In this study, we aimed to investigate the effect of CaBP-9k on cell survival in pancreatic beta cells. Six-month-old wildtype CaBP-9k, CaBP-28k, and CaBP-9k/28k knockout (KO) mice were used to compare the pathological phenotypes of calcium-binding protein-deleted mice. Subsequently, the endoplasmic reticulum (ER) stress reducer tauroursodeoxycholic acid (TUDCA) was administered to wildtype and CaBP-9k KO mice. In vitro assessment of the role of CaBP-9k was performed following CaBP-9k overexpression and treatment with the ER stress inducer thapsigargin. Six-month-old CaBP-9k KO mice showed reduced islet volume and up-regulation of cell death markers resulting from ER stress, which led to pancreatic beta cell death. TUDCA treatment recovered islet volume, serum insulin level, and abdominal fat storage by CaBP-9k ablation. CaBP-9k overexpression elevated insulin secretion and recovered thapsigargin-induced ER stress in the INS-1E cell line. The results of this study show that CaBP-9k can protect pancreatic beta cell survival from ER stress and contribute to glucose homeostasis, which can reduce the risk of type 1 diabetes and provide the molecular basis for calcium supplementation to diabetic patients.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/prevenção & controle , Estresse do Retículo Endoplasmático , Células Secretoras de Insulina/metabolismo , Proteína G de Ligação ao Cálcio S100/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Células Secretoras de Insulina/patologia , Camundongos , Camundongos Knockout , Proteína G de Ligação ao Cálcio S100/genética , Ácido Tauroquenodesoxicólico/farmacologia , Tapsigargina/farmacologia
16.
Sci Rep ; 9(1): 14819, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31616039

RESUMO

The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts.


Assuntos
Autoanticorpos/sangue , Fenômenos Fisiológicos da Nutrição Infantil/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Ilhotas Pancreáticas/imunologia , Metabolismo dos Lipídeos/imunologia , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Autoimunidade , Estudos de Casos e Controles , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Lactente , Ilhotas Pancreáticas/metabolismo , Masculino , Metabolômica , Fatores de Risco
19.
Diabetes Care ; 42(12): 2228-2236, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31558546

RESUMO

OBJECTIVE: To better understand potential facilitators of individual engagement in type 1 diabetes natural history and prevention studies through analysis of enrollment data in the TrialNet Pathway to Prevention (PTP) study. RESEARCH DESIGN AND METHODS: We used multivariable logistic regression models to examine continued engagement of eligible participants at two time points: 1) the return visit after screening to confirm an initial autoantibody-positive (Ab+) test result and 2) the initial oral glucose tolerance test (OGTT) for enrollment into the monitoring protocol. RESULTS: Of 5,387 subjects who screened positive for a single autoantibody (Ab), 4,204 (78%) returned for confirmatory Ab testing. Younger age was associated with increased odds of returning for Ab confirmation (age <12 years vs. >18 years: odds ratio [OR] 2.12, P < 0.0001). Racial and ethnic minorities were less likely to return for confirmation, particularly nonwhite non-Hispanic (OR 0.50, P < 0.0001) and Hispanic (OR 0.69, P = 0.0001) relative to non-Hispanic white subjects. Of 8,234 subjects, 5,442 (66%) were identified as eligible to be enrolled in PTP OGTT monitoring. Here, younger age and identification as multiple Ab+ were associated with increased odds of returning for OGTT monitoring (age <12 years vs. >18 years: OR 1.43, P < 0.0001; multiple Ab+: OR 1.36, P < 0.0001). Parents were less likely to enroll into monitoring than other relatives (OR 0.78, P = 0.004). Site-specific factors, including site volume and U.S. site versus international site, were also associated with differences in rates of return for Ab+ confirmation and enrollment into monitoring. CONCLUSIONS: These data confirm clear differences between successfully enrolled populations and those lost to follow-up, which can serve to identify strategies to increase ongoing participation.


Assuntos
Diabetes Mellitus Tipo 1 , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Autoanticorpos/imunologia , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/prevenção & controle , Feminino , Teste de Tolerância a Glucose , Humanos , Lactente , Modelos Logísticos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Grupos Minoritários/estatística & dados numéricos , Razão de Chances , Adulto Jovem
20.
Biochemistry ; 58(40): 4107-4111, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31523950

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease characterized by an insulin deficiency. Ever since the discovery of insulin almost 100 years ago, patients with T1D have relied on multiple daily insulin injections to survive an otherwise deadly disease. Despite decades of research and clinical trials, no treatment exists yet to prevent or cure T1D. A recent prevention trial using the anti-CD3 antibody teplizumab in individuals at a high risk of developing T1D has provided the first piece of evidence that a safe and transient intervention may be able to delay disease. In this Perspective, we review the 40-year long history of anti-CD3 and discuss how this antibody became a candidate for the treatment of autoimmune diabetes. The path that leads to its use in this latest clinical trial for T1D has been winding and strewn with setbacks. The molecular actions of the anti-CD3 antibody that target T lymphocytes are well-understood, but its systemic effect on immune function has proven more difficult to unravel. Moreover, preclinical data suggested that the utility of anti-CD3 for the prevention of T1D may be limited. However, the latest clinical data are encouraging and exemplify how a basic discovery can, decades later and with much perseverance, become a promising therapeutic candidate.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Complexo CD3/antagonistas & inibidores , Diabetes Mellitus Tipo 1/prevenção & controle , Imunossupressores/uso terapêutico , Animais , Anticorpos Monoclonais Humanizados/imunologia , Complexo CD3/imunologia , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 1/imunologia , Humanos , Imunossupressores/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...