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3.
Lancet ; 394(10205): 1286-1296, 2019 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-31533907

RESUMO

Over several decades, studies have described the progression of autoimmune diabetes, from the first appearance of autoantibodies until, and after, the diagnosis of clinical disease with hyperglycaemia and insulin dependence. Despite the improved management of type 1 diabetes with exogenous insulin, most patients do not meet clinical glycaemic goals, and diabetes remains an important medical problem that affects children and adults. Clinical and preclinical studies have suggested strategies to prevent the diagnosis of type 1 diabetes in people at risk, but the outcomes of previous clinical trials have not met their primary endpoints of disease prevention or delay. The results from the TN-10 teplizumab prevention trial show that the diagnosis of type 1 diabetes can be delayed by treatment with a FcR non-binding monoclonal antibody to CD3 in people at high risk for disease. This Series paper discusses how this clinical achievement raises new questions about for whom, and when, immunological strategies might be developed to prevent type 1 diabetes, and how to achieve this goal.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Anticorpos Monoclonais Humanizados/uso terapêutico , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/imunologia , Humanos
5.
Phytomedicine ; 63: 153002, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31301539

RESUMO

BACKGROUND: Type 1 diabetes is an autoimmune disease directed to the pancreatic islets where inflammation leads to the death of insulin-producing ß cells and insulin deficiency. Type 2 diabetes, which is closely related to overweight, is characterized by insulin resistance. In both cases, proinflammatory cytokines play an important role by causing insulitis and insulin resistance. The gum resin of Boswellia species and its pharmacologically active compounds, including 11-keto-ß-boswellic acids have been shown to suppress the expression of proinflammatory cytokines in various immune-competent cells. PURPOSE: To review the present evidence of the therapeutic effects of boswellic extracts (BE) and/or 11-keto-ß-boswellic acids in the prevention/treatment of diabetes mellitus and to provide comprehensive insights into the underlying molecular mechanisms. METHODS: This review considers all available informations from preclinical and clinical studies concerning BEs, 11-keto-ß-boswellic acids, proinflammatory cytokines and diabetes mellitus collected via electronic search (PubMed) and related publications of the author. RESULTS: Type 1 diabetes: Studies in mice with autoimmune diabetes revealed that in the model of multiple injections of low doses of streptozotocin (MLD-STZ), an extract of the gum resin of Boswellia serrata and 11-keto-ß-boswellic acid (KBA) suppressed the increase in proinflammatory cytokines in the blood, infiltration of lymphocytes into pancreatic islets and increase in blood glucose. In a second model, i.e. the nonobese diabetic (NOD) mouse, KBA prevented the infiltration of lymphocytes into pancreatic islets. Regarding the clinical effects, a case report provided evidence that BE suppressed the blood levels of tyrosine phosphatase antibody (IA2-A), a marker for insulitis, in a patient with late-onset autoimmune diabetes of the adult (LADA). Type 2 diabetes: In a preclinical study in rats where obesity was alimentary induced, the administration of BE significantly reduced food intake, overweight, proinflammatory cytokines such as interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) and ameliorated the parameters of glucose and lipid metabolism. Similar results were obtained in a second animal study, where type 2 diabetes was induced by a combination of a high-fat/high-fructose diet and a single dose of streptozotocin. Two clinical trials with patients with type 2 diabetes receiving the resin of Boswellia serrata demonstrated improvement in the blood glucose, HbA1c and lipid parameters. CONCLUSION: Preclinical and clinical data suggest that BE and/or 11-keto-ß-boswellic acids by inhibiting the expression of proinflammatory cytokines from immune-competent cells, may prevent insulitis and insulin resistance in type 1 and type 2 diabetes, respectively, and therefore may be an option in the treatment/prevention of type 1 and type 2 diabetes. It is hypothesized that molecularly, BE and 11-keto-ß-boswellic acids act via interference with the IκB kinase/Nuclear Transcription Factor-κB (IKK/NF-κB) signaling pathway through inhibition of the phosphorylation activity of IKK. However, further investigations and well-designed clinical studies are required.


Assuntos
Boswellia/química , Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Extratos Vegetais/farmacologia , Animais , Citocinas/sangue , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Humanos , Insulina/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Camundongos , Camundongos Endogâmicos NOD , NF-kappa B/metabolismo , Extratos Vegetais/química , Ratos , Resinas Vegetais/química , Resinas Vegetais/farmacologia , Triterpenos/farmacologia
6.
Rev Med Chil ; 147(4): 451-457, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344206

RESUMO

BACKGROUND: Few studies have evaluated the details of insulin therapy for type 1 diabetes mellitus (T1D) in Chile. AIM: To describe clinical features and treatment details of adults with T1D and its association with metabolic control. MATERIAL AND METHODS: Review of medical records of patients with T1D treated in a clinical network. Demographic and clinical features, types and doses of insulin and glycated hemoglobin levels were registered. The use flash glucose monitors (FGM) and insulin pumps (CSII) were also recorded. RESULTS: 205 records were reviewed, with T1d lasting 12 ± 10 years. Twenty six percent had hypothyroidism, 1% had celiac disease, 12% had hypertension, 20% had dyslipidemia; 13% had diabetic retinopathy, 2% had diabetic nephropathy, 8% had neuropathy and 2% cardiovascular diseases. Mean body mass index was 25 kg/ m2 and mean glycated hemoglobin was 8%. Eighty-two percent used multiple daily injections, 18% used CSII and 24% used FGM. As basal insulin, 35% used slow acting analogs and 65% used ultra-slow analogs. As rapid acting insulin, 69 patients used Lispro, 79 Aspart and 50 Glulisin. Bolus doses were calculated using only capillary glucose in 22%, while 78% also considered carbohydrate consumption. Variables significantly associated to better control were the use of carbohydrates for dosing rapid insulin (A1c 7,85% vs 8,59%, p = 0,008), use of CSII (A1c 7,36% vs 8,16%, p = 0,008), and basal dose < 0,4 U/kg (A1c 7,81% vs 8,58%, p = 0,003). There were no differences regarding insulin type or use of FGM. CONCLUSIONS: The use of formulas considering carbohydrates for dosing rapid insulin, use of infusion pumps and physiological doses of basal insulin are significantly associated with a better metabolic control in adults with T1d.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Adulto , Análise de Variância , Chile , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Hemoglobina A Glicada/análise , Humanos , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
N Engl J Med ; 381(7): 603-613, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31180194

RESUMO

BACKGROUND: Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed. METHODS: We conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor-nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease. Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals. RESULTS: A total of 76 participants (55 [72%] of whom were ≤18 years of age) underwent randomization - 44 to the teplizumab group and 32 to the placebo group. The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo. The hazard ratio for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (95% confidence interval, 0.22 to 0.78; P = 0.006 by adjusted Cox proportional-hazards model). The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group. There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group. Among the participants who were HLA-DR3-negative, HLA-DR4-positive, or anti-zinc transporter 8 antibody-negative, fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed. CONCLUSIONS: Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01030861.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Complexo CD3/antagonistas & inibidores , Diabetes Mellitus Tipo 1/prevenção & controle , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Criança , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Progressão da Doença , Método Duplo-Cego , Exantema/induzido quimicamente , Feminino , Teste de Tolerância a Glucose , Antígeno HLA-DR3 , Antígeno HLA-DR4 , Humanos , Contagem de Linfócitos , Linfopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Linfócitos T/imunologia , Adulto Jovem
9.
Diabetes Res Clin Pract ; 154: 1-8, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31220483

RESUMO

AIMS: Women with pre-existing diabetes should plan for optimal care of the disease before, during and after pregnancy. The aim of this study was to assess the quality of diabetes mellitus monitoring and care before, during and after pregnancy in a large cohort of women. METHODS: 1913 diabetic women resident in the Lombardy Region (Italy) who experienced at least a birth between 2011 and 2015 and exhibited signs of diabetes ≥2 years before delivery were identified using the healthcare utilization database. Antidiabetic care was defined via outpatient examinations (i.e., assessments of glycated haemoglobin, lipid profile, urine albumin excretion and serum creatinine, and dilated eye exams) and use of antidiabetic drugs. Differences in adherence to recommendations before, during and after pregnancy were assessed by the non-parametric McNemar's test among the whole cohort and among the subgroup with type 1 diabetes. RESULTS: Adherence to recommendations was very poor before pregnancy, ranging from 13% to 42% for dilated eye and serum creatinine exam, respectively. During pregnancy, a significant portion of women increased adherence to all recommendations (e.g., glycated haemoglobin from 20% to 47%, p-value < 0.001), with the exception of lipid profile control. After pregnancy, adherence dropped to pre-pregnancy levels. A similar trend was observed in the use of antidiabetic drugs. Although women with type 1 diabetes showed better adherence across all periods, the same patterns emerged. CONCLUSIONS: Besides an improvement in the indicators of clinical adherence during pregnancy, the management of diabetes among pregnant women remains sub-optimal both before and after the birth.


Assuntos
Biomarcadores/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Cooperação do Paciente/estatística & dados numéricos , Gravidez em Diabéticas/sangue , Adolescente , Adulto , Estudos de Coortes , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Hipoglicemiantes , Itália/epidemiologia , Pessoa de Meia-Idade , Gravidez , Gravidez em Diabéticas/epidemiologia , Gravidez em Diabéticas/prevenção & controle , Prognóstico , Adulto Jovem
10.
PLoS One ; 14(4): e0215636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31009496

RESUMO

PURPOSE: Non-communicable chronic diseases have become the leading causes of mortality and disease burden worldwide. With information about the frequency of diabetes as a major non-communicable chronic disease in Russia being scarce, we assessed the prevalence of diabetes and its associated factors in a rural and urban population in Russia. METHODS: The Ural Eye and Medical Study is a population-based study in the city of Ufa/Russia and in villages in a distance of 65 km from Ufa. Inclusion criterion was an age of 40+ years. All study participants underwent a standardized interview and a detailed general examination. Diabetes mellitus was defined by a plasma glucose concentration ≥7.0 mmol/L or self-reported history of physician diagnosis of diabetes. RESULTS: Out of a population of 7328 eligible individuals, 5899 individuals (2580 (43.7%) men) (participation rate:80.5%) participated (mean age:59.0±10.7 years (range:40-94 years)). Diabetes mellitus was present in 687 individuals (11.7%;95% confidence interval (CI):11.9,12.5). Awareness rate of having diabetes was 500/687 (72.8%;95%CI:69.0,76.0), with mean known duration of diabetes of 10.0±9.4 years. Known type 1 diabetes was present in 44 subjects and known type 2 diabetes in 358 subjects. Prevalence of undiagnosed diabetes was 3.2% (95%CI:2.7,3.6) in the study population. Among patients with diabetes, 59.1% (95%CI:55.4,62.8) received treatment for diabetes, among whom 237 (58.5%;95%CI:53.7,63.3) individuals had adequate glycemic control. In multivariable analysis, higher prevalence of diabetes mellitus was associated with older age (P<0.001; odds ratio (OR):1.03;95%CI:1.01,1.04), higher body mass index (P<0.001;OR:1.07;95%CI:1.04,1.10), lower prevalence of vigorous daily work (P = 0.002;OR0.68;95%CI:0.53,0.87), positive history of arterial hypertension (P = 0.03;OR:1.40;95%CI:1.03,1.89) and cardiovascular diseases (P = 0.001;OR:1.60;95%CI:1.21,2.13) including heart attacks (P = 0.01;OR:1.80;95%CI:1.15,2.81), higher serum concentration of triglycerides (P<0.001;OR:1.51;95%CI:1.30,1.75), higher systolic blood pressure (P = 0.01;OR:1.01;95%CI:1.01,1.02), higher number of meals taken daily (P<0.001;OR:1.46;95%CI:1.25,1.69), and non-Muslim religion (P = 0.02;OR:0.73;95%CI:0.56,0.94). CONCLUSIONS: In this ethnically mixed, urban and rural Russian population aged 40+ years, the awareness rate of diabetes (72.8%) was relatively high, while the diabetes prevalence (11.7%) was comparable with that of other countries such as China and the USA. Factors associated with higher diabetes prevalence were similar in Russia and these other countries and included older age, higher body mass index and higher serum concentration of triglycerides, lower prevalence of vigorous daily work, arterial hypertension and cardiovascular diseases.


Assuntos
Conscientização , Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Federação Russa/epidemiologia
11.
Int J Mol Sci ; 20(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987262

RESUMO

Antigen-presenting cells (APCs) including dendritic cells (DCs) play a critical role in the development of autoimmune diseases by presenting self-antigen to T-cells. Different signals modulate the ability of APCs to activate or tolerize autoreactive T-cells. Since the expression of heme oxygenase-1 (HO-1) by APCs has been associated with the tolerization of autoreactive T-cells, we hypothesized that HO-1 expression might be altered in APCs from autoimmune-prone non-obese diabetic (NOD) mice. We found that, compared to control mice, NOD mice exhibited a lower percentage of HO-1-expressing cells among the splenic DCs, suggesting an impairment of their tolerogenic functions. To investigate whether restored expression of HO-1 in APCs could alter the development of diabetes in NOD mice, we generated a transgenic mouse strain in which HO-1 expression can be specifically induced in DCs using a tetracycline-controlled transcriptional activation system. Mice in which HO-1 expression was induced in DCs exhibited a lower Type 1 Diabetes (T1D) incidence and a reduced insulitis compared to non-induced mice. Upregulation of HO-1 in DCs also prevented further increase of glycemia in recently diabetic NOD mice. Altogether, our data demonstrated the potential of induction of HO-1 expression in DCs as a preventative treatment, and potential as a curative approach for T1D.


Assuntos
Diabetes Mellitus Tipo 1/enzimologia , Diabetes Mellitus Tipo 1/prevenção & controle , Heme Oxigenase-1/genética , Animais , Antígeno CD11c/metabolismo , Células Dendríticas/metabolismo , Diabetes Mellitus Tipo 1/complicações , Doxiciclina/farmacologia , Hiperglicemia/complicações , Hiperglicemia/prevenção & controle , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Regulação para Cima/efeitos dos fármacos
12.
Am J Clin Nutr ; 109(Suppl_7): 817S-837S, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30982877

RESUMO

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the US Departments of Agriculture and Health and Human Services initiated a review of evidence on diet and health in these populations. OBJECTIVES: The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding, and 4) feeding a lower versus higher intensity of human milk to mixed-fed infants with type 1 and type 2 diabetes in offspring. METHODS: The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January 1980-March 2016, dual-screened the results according to predetermined criteria, extracted data from and assessed the risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: The 4 systematic reviews included 21, 37, 18, and 1 articles, respectively. Observational evidence suggests that never versus ever feeding human milk (limited evidence) and shorter versus longer durations of any (moderate evidence) and exclusive (limited evidence) human milk feeding are associated with higher type 1 diabetes risk. Insufficient evidence examined type 2 diabetes. Limited evidence suggests that the durations of any and exclusive human milk feeding are not associated with intermediate outcomes (e.g., fasting glucose, insulin resistance) during childhood. CONCLUSIONS: Limited to moderate evidence suggests that feeding less or no human milk is associated with higher risk of type 1 diabetes in offspring. Limited evidence suggests no associations between the durations of any and exclusive human milk feeding and intermediate diabetes outcomes in children. Additional research is needed on infant milk-feeding practices and type 2 diabetes and intermediate outcomes in US populations, which may have distinct metabolic risk.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Dieta , Comportamento Alimentar , Fórmulas Infantis , Leite Humano , Aleitamento Materno , Criança , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/prevenção & controle , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , Lactente , Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido
13.
Can J Diabetes ; 43(5): 345-353, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30853267

RESUMO

OBJECTIVES: Heat preconditioning and heat-shock protein (HSP) synthesis have significant cytoprotective effects against the development of cellular injury caused by the application of a subsequent stressor, which were found to depend on the time period between the stressors. We aimed to determine the most efficient recovery time (6 h or 24 h) following heat-stress exposure and prior application of diabetic streptozotocin (STZ) on the moderation of carbohydrate and oxidative metabolic disturbances caused by diabetes. METHODS: Experiment animals (Wistar rats) were exposed to acute heat stress at 41±1°C for 45 min, followed by 6-h or 24-h recovery times at room temperature before sacrifice or STZ administration. RESULTS: Our findings indicate that acute heat stress with 6-h or 24-h recovery periods results in a significant rise in the hepatic heat-shock protein 70 (HSP70) levels (even more so after 24 h), glycogen breakdown and stable glycemia, followed by reduced glycolytic and gluconeogenic activity (after 24 h) (glucose-6-phosphatase, fructose-1,6-bisphosphatase); stimulates antioxidative activity (glutathione peroxidase, glutathione reductase) (after 6 h); and decreases glutathione and catalase activity (after 24 h). Heat preconditioning (with 6-h and 24-h recovery periods) prior to STZ-induced diabetes increases HSP70 levels and causes lower serum glucose levels, higher glycogen and glucose-6-phosphate levels, lower glucose-6-phosphatase levels and glycogen phosphorylase and hexokinase levels but also elevates glutathione reductase and glutathione peroxidase activity compared to untreated STZ animals. CONCLUSIONS: Based on our findings, heat preconditioning and HSP70 induction in rats with type 1 diabetes attenuates STZ-induced metabolic alterations in hepatic carbohydrate metabolism and oxidative states. These changes are more evident at 24 h recovery post-acute heat stress, based on the most evident accumulation of HSP70 in this time frame.


Assuntos
Metabolismo dos Carboidratos , Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 1/prevenção & controle , Proteínas de Choque Térmico HSP70/metabolismo , Hipertermia Induzida , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , Temperatura Corporal , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Feminino , Glutationa/metabolismo , Resposta ao Choque Térmico , Fígado , Oxirredução , Ratos , Ratos Wistar
15.
An. pediatr. (2003. Ed. impr.) ; 90(3): 173-179, mar. 2019. tab
Artigo em Espanhol | IBECS | ID: ibc-178370

RESUMO

Introducción: El alumnado con diabetes tipo 1 (DM1) requiere durante su estancia en el centro educativo unos cuidados adecuados y seguros para su enfermedad. Objetivo: Identificar las necesidades percibidas por las familias del alumnado con DM1 que afecten a la integración educativa, seguridad y bienestar durante la jornada educativa. Métodos: Estudio descriptivo y transversal, mediante encuesta, basado en la información y opiniones proporcionada por las familias de los 362 pacientes entre 3 y 16 años con DM1, registrados en la historia de salud del Sistema Sanitario Público de Extremadura. Resultados: Tasa de respuesta del 56,9% (206). El 35% del alumnado con DM1 estaba en tratamiento con infusión subcutánea continua de insulina. El 95,1% precisó medir la glucemia y el 57,8% administrarse insulina durante la jornada escolar. Un 88% presentó buena adaptación al colegio y el 87,4% no describió ningún tipo de trato discriminatorio. El 82% de centros dispuso de glucagón y en un 43,7% hubo alguna persona adulta entrenada para administrarlo. Un 21,4% de familias pensaban que los profesores podían reconocer una hipoglucemia. El 29,1% desconocían la existencia de protocolos de coordinación en centros educativos, el 58,7% alegaron que la información en el centro sobre diabetes fue poca y un 77,2% que su control mejoraría con más formación del profesorado. Conclusiones: Existen aspectos óptimamente cubiertos en la atención al alumnado con DM1 en los centros educativos de Extremadura. Las situaciones con margen de mejora son la adherencia al protocolo de coordinación, la información sobre la diabetes y el adiestramiento de adultos ante emergencias


Introduction: School-aged children with type 1 diabetes (DM1) require access to appropriate and safe care for their disease during their stay in the educational centre. Objective: To identify the needs perceived by families of schoolchildren with DM1 that affect their educational integration, safety, and well-being during the school day. Methodology: A descriptive and cross-sectional study was conducted using a questionnaire based on information and opinions provided by families of 362 schoolchildren between 3 and 16 years old with DM1 registered in their health history in the Public Health System of Extremadura. Results: The response rate was 56.9% (206). It was shown that 35% of schoolchildren with DM1 were treated with continuous subcutaneous insulin infusion therapy. Almost all of them (95.1%) required glucose monitoring, and 57.8% required insulin administration during the school day. Most (88%) children had adjusted well to school and did not describe any type of discriminatory treatment (87.4%). Glucagon is available in 82% of educational centres, in which 43.7% had a trained adult person to administer it. That teachers could recognise a hypoglycaemia was expressed by 21.4% of the families, and 29.1% were unaware of the existence of coordination protocols in the school. More than half (58.7%) claimed that the information available in schools about diabetes was low, and 77.2% stated that the control of the disease would improve if more training was provided to teachers. Conclusions: There are aspects optimally covered in the care of schoolchildren with DM1 in the schools of Extremadura. Among situations identified with potential room for improvement were adherence to the coordination protocol, information about diabetes, and training of adults to deal with emergency situations


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/prevenção & controle , Determinação de Necessidades de Cuidados de Saúde , Percepção , Família , Inclusão Educacional , Estudos Transversais , Sistemas Nacionais de Saúde , Necessidades e Demandas de Serviços de Saúde , Insulina/uso terapêutico
16.
Parasitol Res ; 118(4): 1087-1094, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30758662

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease in which cells of the immune system destroy pancreatic ß cells, which secrete insulin. The high prevalence of T1D in developed societies may be explained by environmental changes, including lower exposure to helminths. Indeed, infection by helminths such as Schistosoma, Filaria, and Heligmosomoides polygyrus and their by-products has been reported to ameliorate or prevent the development of T1D in human and animal models. Helminths can trigger distinct immune regulatory pathways, often involving adaptive immune cells that include T helper 2 (Th2) cells and regulatory T cells (Tregs) and innate immune cells that include dendritic cells, macrophages, and invariant natural killer T cells, which may act synergistically to induce Tregs in a Toll-like receptor-dependent manner. Cytokines such as interleukin (IL)-4, IL-10, and transforming growth factor (TGF)-ß also play an important role in protection from T1D. Herein, we provide a comprehensive review of the effects and mechanisms underlying protection against T1D by helminths.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Helmintos/imunologia , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/patologia , Linfócitos T Reguladores/imunologia , Animais , Células Dendríticas/imunologia , Diabetes Mellitus Tipo 1/patologia , Humanos , Interleucina-10/imunologia , Interleucina-4/imunologia , Macrófagos/imunologia , Células T Matadoras Naturais/imunologia , Células Th2/imunologia , Fator de Crescimento Transformador beta/imunologia
17.
Life Sci ; 221: 301-310, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30776371

RESUMO

AIMS: Recent studies have revealed that neutrophil extracellular traps (NETs) provide negative feedback in the progression to chronic inflammation and contribute to the pathogenesis of multiple autoimmune diseases including type 1 diabetes (T1D). In addition, accumulating evidences suggest that gut immunity play a key role in T1D pathogenesis. Our study aimed to evaluate whether staphylococcal nuclease (SNase) targeting intestinal NETs can ameliorate the intestinal inflammatory environment and protect against T1D development in non-obese diabetic(NOD) mice. MAIN METHODS: Degradation of NETs with SNase in vitro was examined using SYTOX green assay. NOD/LtJ mice were oral administration of Lactococcus lactisl (L. lactis) pCYT: SNase and blood glucose levels were monitored weekly. Several biomarkers of NETs formation, gut leakage and inflammation were determined using a commercial ELISA kit. T Cell phenotypes in peripheral immune system were analyzed in flow cytometry and fecal samples were isolated to investigate intestinal microbiota. KEY FINDINGS: The oral delivery of SNase by L. lactis can decrease the NETs levels and ameliorate inflammation both in the intestine and pancreatic islets and finally effectively regulate the blood glucose levels of NOD mice. Meanwhile, zonulin and lipopolysaccharide levels also reduced in SNase-fed NOD mice, suggesting SNase could improve gut barrier function via intestinal NETs degradation. Furthermore, the abundances of the intestinal microbiota and butyrate-producing gut bacteria were also increased with SNase treatment. SIGNIFICANCE: SNase shows potential for intestinal NETs to prevent T1D based on the gut-pancreas axis.


Assuntos
Armadilhas Extracelulares/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/fisiologia , Animais , Glicemia , Diabetes Mellitus Tipo 1/prevenção & controle , Modelos Animais de Doenças , Inflamação , Intestinos , Ilhotas Pancreáticas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos NOD , Nuclease do Micrococo/farmacologia
19.
Eur J Clin Nutr ; 73(1): 1-8, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29765164

RESUMO

BACKGROUND/OBJECTIVES: The association between the intake of polyunsaturated fatty acids (PUFAs) and the risk of preclinical and clinical type 1 diabetes (T1D) in children has generated conflicting results. Thus, we aimed to evaluate the definite effects of PUFAs on the risk of preclinical and clinical T1D. SUBJECTS/METHODS: Three databases were systematically searched up to July 18, 2017 to identify relevant observational studies, without language restriction. Any study included should report the risk of preclinical or clinical T1D in children with PUFAs supplementation compared with the controls, and report relative risks (RRs) or odds ratios (ORs) or provide data for estimation. Pooled RRs (or ORs) with 95% confidence intervals (CI) were calculated using random-effects models irrespective of statistical heterogeneity assessed by I2 statistic. RESULTS: We identified seven studies (three prospective cohort studies and four case-control studies) on PUFAs intake during pregnancy or during early life in children. The pooled RR between the risk of preclinical T1D and n-3 PUFAs supplementation against controls was 0.98 (95%CI, 0.85-1.13), with no heterogeneity. The results were similar after the intake during pregnancy, but not during early life in children (pooled RR, 0.45; 95%CI, 0.21-0.96; P = 0.039). N-3 PUFAs supplementation was not associated with a significant reduction in the risk of clinical T1D in children (pooled RR, 0.87; 95%CI, 0.71-1.08), with substantial heterogeneity(I2 = 64.7%). No association was also found between n-6 PUFAs intake and the risk of preclinical (1.07; 0.97-1.017) or clinical T1D (1.05; 0.92-1.20) in children. CONCLUSIONS: The result of the meta-analysis does not support that n-3 or n-6 PUFAs supplementation in children affects the overall risk of preclinical or clinical T1D. However, n-3 PUFAs intake in early life might reduce the risk of preclinical T1D. Therefore, this finding should be verified by more and well-designed prospective research in the future.


Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Estado Pré-Diabético/prevenção & controle , Estudos de Casos e Controles , Criança , Diabetes Mellitus Tipo 1/etiologia , Feminino , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Razão de Chances , Estado Pré-Diabético/etiologia , Gravidez , Estudos Prospectivos , Fatores de Risco
20.
Environ Sci Pollut Res Int ; 26(2): 1370-1378, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30426368

RESUMO

Exposure to environmental chemicals can modulate the developing immune system, but its role in the pathogenesis of type 1 diabetes is largely unexplored. Our objective was to study the levels of circulating concentrations of environmental pollutants during the first years of life and their associations with the later risk of diabetes-predictive autoantibodies. From two birth-cohort studies including newborn infants with HLA-conferred susceptibility to type 1 diabetes (FINDIA and DIABIMMUNE), we identified case children with at least one biochemical diabetes-associated autoantibody (n = 30-40) and from one to four autoantibody-negative controls per each case child matched for age, gender, diabetes-related HLA-risk, delivery hospital, and, in FINDIA, also dietary intervention group. Plasma levels of 13 persistent organic pollutants and 14 per- and polyfluorinated substances were analyzed in cord blood and plasma samples taken at the age of 12 and 48 months. Both breastfeeding and the geographical living environment showed association with circulating concentrations of some of the chemicals. Breastfeeding-adjusted conditional logistic regression model showed association between decreased plasma HBC concentration at 12-month-old children and the appearance of diabetes-associated autoantibodies (HR, 0.989; 95% Cl, 0.978-1.000; P = 0.048). No association was found between the plasma chemical levels and the development of clinical type 1 diabetes. Our results do not support the view that exposure to the studied environmental chemicals during fetal life or early childhood is a significant risk factor for later development of ß-cell autoimmunity and type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/etiologia , Poluentes Ambientais/sangue , Células Secretoras de Insulina/imunologia , Autoanticorpos/sangue , Autoimunidade , Aleitamento Materno , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Dieta , Feminino , Sangue Fetal/química , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores de Risco
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