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1.
Curr Diab Rep ; 20(9): 46, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32803436

RESUMO

PURPOSE OF REVIEW: The underlying factors triggering a cascade of autoimmune response that leads to the death of pancreatic beta cells and type 1 diabetes are to large extent unknown. Aberrations in the lipid balance have been suggested, either as factors directly contributing to autoimmunity or as a reflection of external factors, such as the diet or chemical exposure, which may increase the risk or even trigger the autoimmunity cascade. RECENT FINDINGS: A small number of recent studies have investigated the blood lipidome before and after the onset of type 1 diabetes with a goal of identifying biomarkers of disease progression. Phosphatidylcholine levels in particular have been suggested to be reduced prior to the onset of type 1 diabetes. In this review, we approach this question through a quantitative analysis of the reported lipids. We quantify the extent of consensus between these heterogeneous studies, describe the overall lipidomic pattern that has been reported, and call for more independent replication of the findings that we highlight in this review.


Assuntos
Diabetes Mellitus Tipo 1 , Biomarcadores , Diabetes Mellitus Tipo 1/etiologia , Humanos , Metabolismo dos Lipídeos , Lipidômica , Lipídeos
2.
Pediatr Endocrinol Rev ; 17(4): 284-286, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32780950

RESUMO

Recent epidemiological surveys performed in Australia, USA and Israel demonstrate that Rotavirus vaccination correlates with an attenuated prevalence and/or incidence of early childhood diabetes (T1D). Other studies failed to confirm the above.


Assuntos
Diabetes Mellitus Tipo 1 , Infecções por Rotavirus , Vacinas Virais/efeitos adversos , Criança , Diabetes Mellitus Tipo 1/etiologia , Gastroenterite , Humanos , Incidência , Israel , Vacinação
3.
Curr Opin Endocrinol Diabetes Obes ; 27(4): 187-193, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618630

RESUMO

PURPOSE OF REVIEW: To summarize a new form of autoimmune diabetes as an adverse event of specific cancer immunotherapies. Immune checkpoint inhibitors are revolutionary treatments in advanced cancers; however, they can cause type 1 diabetes following treatment with these state-of-the-art therapies. RECENT FINDINGS: A review of the literature showed that this new form of autoimmune diabetes has significant similarities with childhood-onset type 1 diabetes but also some distinctions. It frequently presents with severe diabetic ketoacidosis and almost half of the patients have type 1 diabetes-associated antibodies at presentation. Rapid loss of residual beta-cell function with a lack of honeymoon phase is typical. Certain human leukocyte antigen risk genes for prototypical type 1 diabetes that develops in children and young adults are also commonly found in patients with immune checkpoint inhibitor-induced type 1 diabetes. SUMMARY: Immune checkpoint inhibitor-induced type 1 diabetes presenting with diabetic ketoacidosis is a life-threatening adverse event of cancer immunotherapy. Healthcare providers should be aware of this adverse event to prevent morbidity and mortality related to diabetic ketoacidosis. Developing guidelines to identify and monitor risk groups are of utmost importance.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Diabetes Mellitus Tipo 1/etiologia , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Pontos de Checagem do Ciclo Celular/imunologia , Criança , Diabetes Mellitus Tipo 1/imunologia , Cetoacidose Diabética/etiologia , Cetoacidose Diabética/imunologia , Humanos , Imunoterapia/efeitos adversos , Neoplasias/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Adulto Jovem
4.
Curr Opin Endocrinol Diabetes Obes ; 27(4): 215-224, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618633

RESUMO

PURPOSE OF REVIEW: Emerging data have suggested that ß-cell dysfunction may exacerbate the development and progression of type 1 diabetes (T1D). In this review, we highlight clinical and preclinical studies suggesting a role for ß-cell dysfunction during the evolution of T1D and suggest agents that may promote ß-cell health in T1D. RECENT FINDINGS: Metabolic abnormalities exist years before development of hyperglycemia and exhibit a reproducible pattern reflecting progressive deterioration of ß-cell function and increases in ß-cell stress and death. Preclinical studies indicate that T1D may be prevented by modification of pathways impacting intrinsic ß-cell stress and antigen presentation. Recent findings suggest that differences in metabolic phenotypes and ß-cell stress may reflect differing endotypes of T1D. Multiple pathways representing potential drug targets have been identified, but most remain to be tested in human populations with preclinical disease. SUMMARY: This cumulative body of work shows clear evidence that ß-cell stress, dysfunction, and death are harbingers of impending T1D and likely contribute to progression of disease and insulin deficiency. Treatment with agents targeting ß-cell health could augment interventions with immunomodulatory therapies but will need to be tested in intervention studies with endpoints carefully designed to capture changes in ß-cell function and health.


Assuntos
Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/fisiopatologia , Células Secretoras de Insulina/fisiologia , Diabetes Mellitus Tipo 1/metabolismo , Progressão da Doença , Humanos , Hiperglicemia/sangue , Hiperglicemia/complicações , Hiperglicemia/patologia , Hiperglicemia/fisiopatologia , Insulina/deficiência , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia
5.
Curr Opin Endocrinol Diabetes Obes ; 27(4): 231-239, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618635

RESUMO

PURPOSE OF REVIEW: New single-cell tec. hnologies developed over the past decade have considerably reshaped the biomedical research landscape, and more recently have found their way into studies probing the pathogenesis of type 1 diabetes (T1D). In this context, the emergence of mass cytometry in 2009 revolutionized immunological research in two fundamental ways that also affect the T1D world: first, its ready embrace by the community and rapid dissemination across academic and private science centers alike established a new standard of analytical complexity for the high-dimensional proteomic stratification of single-cell populations; and second, the somewhat unexpected arrival of mass cytometry awoke the flow cytometry field from its seeming sleeping beauty stupor and precipitated substantial technological advances that by now approach a degree of analytical dimensionality comparable to mass cytometry. RECENT FINDINGS: Here, we summarize in detail how mass cytometry has thus far been harnessed for the pursuit of discovery studies in T1D science; we provide a succinct overview of other single-cell analysis platforms that already have been or soon will be integrated into various T1D investigations; and we briefly consider how effective adoption of these technologies requires an adjusted model for expense allocation, prioritization of experimental questions, division of labor, and recognition of scientific contributions. SUMMARY: The introduction of contemporary single-cell technologies in general, and of mass cytometry, in particular, provides important new opportunities for current and future T1D research; the necessary reconfiguration of research strategies to accommodate implementation of these technologies, however, may both broaden research endeavors by fostering genuine team science, and constrain their actual practice because of the need for considerable investments into infrastructure and technical expertise.


Assuntos
Pesquisa Biomédica/tendências , Ciência de Dados/tendências , Diabetes Mellitus Tipo 1/etiologia , Proteômica/métodos , Análise de Célula Única/tendências , Animais , Pesquisa Biomédica/história , Pesquisa Biomédica/métodos , Ciência de Dados/história , Ciência de Dados/métodos , Diabetes Mellitus Tipo 1/patologia , Citometria de Fluxo/história , Citometria de Fluxo/métodos , Citometria de Fluxo/tendências , História do Século XXI , Humanos , Espectrometria de Massas/história , Espectrometria de Massas/métodos , Espectrometria de Massas/tendências , Proteômica/história , Proteômica/tendências , Análise de Célula Única/história , Análise de Célula Única/métodos
6.
Nat Rev Endocrinol ; 16(7): 349-362, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32398822

RESUMO

Loss of functional ß-cell mass is the key mechanism leading to the two main forms of diabetes mellitus - type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Understanding the mechanisms behind ß-cell failure is critical to prevent or revert disease. Basic pathogenic differences exist in the two forms of diabetes mellitus; T1DM is immune mediated and T2DM is mediated by metabolic mechanisms. These mechanisms differentially affect early ß-cell dysfunction and eventual fate. Over the past decade, major advances have been made in the field, mostly delivered by studies on ß-cells in human disease. These advances include studies of islet morphology and human ß-cell gene expression in T1DM and T2DM, the identification and characterization of the role of T1DM and T2DM candidate genes at the ß-cell level and the endoplasmic reticulum stress signalling that contributes to ß-cell failure in T1DM (mostly IRE1 driven) and T2DM (mostly PERK-eIF2α dependent). Here, we review these new findings, focusing on studies performed on human ß-cells or on samples obtained from patients with diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Pancreática Exócrina/etiologia , Células Secretoras de Insulina/fisiologia , Animais , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Insuficiência Pancreática Exócrina/fisiopatologia , Humanos , Células Secretoras de Insulina/patologia , Transdução de Sinais/fisiologia
8.
Sultan Qaboos Univ Med J ; 20(1): e5-e12, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32190364

RESUMO

The association between breastfeeding and type 1 diabetes mellitus (T1DM) is controversial. However, several recent studies have established a link between these two factors, necessitating a need to review this subject to raise public awareness. Current research indicates that breast milk contains a variety of bioactive substances including immunoglobulins, oligosaccharides, insulin, lactoferrin, lysozyme, cytokines, epidermal growth factors, leukocytes, nucleotides, beneficial bacteria and vitamins. Such substances strengthen the breastfeeding infant's immune system, both directly, by increasing gut microbiota diversity and attacking harmful bacteria and pro-inflammatory molecules, and indirectly, by increasing thymus performance. Accordingly, a lack of or inadequate breastfeeding may predispose infants to several autoimmune disorders, including T1DM. Nursing mothers and caregivers are therefore advised to follow optimal breastfeeding practices prior to introducing complementary foods.


Assuntos
Fatores Biológicos/análise , Diabetes Mellitus Tipo 1/etiologia , Leite Humano/química , Adulto , Aleitamento Materno , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
9.
Rev. cuba. oftalmol ; 33(1): e692, ene.-mar. 2020. tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1126725

RESUMO

RESUMEN Objetivo: Identificar las características morfológicas del epitelio, el estroma y el endotelio corneal, así como la densidad celular de este último mediante el empleo de la microscopia confocal de la córnea en pacientes diabéticos. Métodos: Se realizó un estudio descriptivo, comparativo, en 90 ojos; 60 de ellos pertenecientes a pacientes diabéticos (30 tipo 1 y 30 tipo 2) y 30 ojos a pacientes supuestamente sanos. El estudio se realizó en el Instituto Cubano de Oftalmología "Ramón Pando Ferrer" entre enero del año 2012 y enero de 2017. Resultados: Predominó el sexo masculino con 66,7 por ciento en los pacientes con diabetes mellitus tipo 1; el sexo femenino en los pacientes con diabetes mellitus tipo 2 (60 por ciento) y aparentemente sanos (56,7 por ciento). En los pacientes con diabetes mellitus tipo 1 fueron más frecuentes las edades entre 45 y 54 años (33,3 por ciento) y entre 55 y 66 años en los pacientes con diabetes mellitus tipo 2 y aparentemente sanos con 60 y 40 por ciento respectivamente. La morfología del epitelio y el estroma corneal fue normal en el 86,7 y 87,3 por ciento respectivamente. Predominaron las alteraciones de la morfología endotelial en pacientes diabéticos tipo 1 (73,3 por ciento), así como el polimegatismo y el pleomorfismo (73,3 y 56,7 por ciento respectivamente) y la densidad celular más baja (2 222,76 células /mm2). Conclusiones: La ausencia de alteraciones morfológicas del epitelio y el estroma corneal y la presencia de polimegatismo y de pleomorfismo fueron los hallazgos más frecuentes(AU)


ABSTRACT Objective: Identify the morphological characteristics of the corneal epithelium, stroma and endothelium, as well as the cell density of the endothelium by means of confocal microscopy of the cornea in diabetic patients. Methods: A descriptive comparative study was conducted of 90 eyes: 60 from diabetic patients (30 type 1 and 30 type 2) and 30 from supposedly healthy patients, at Ramón Pando Ferrer Cuban Institute of Ophthalmology from January 2012 to January 2017. Results: A predominance was found of the male sex (66.7 percent) among patients with diabetes mellitus type 1 and of the female sex among patients with diabetes mellitus type 2 (60 percent) and seemingly healthy patients (56.7 percent). The most common age ranges were 45-54 years for patients with diabetes mellitus type 1 (33.3 percent) and 55-66 years for patients with diabetes mellitus type 2 (60 percent) and seemingly healthy patients (40 percent). Morphology of the corneal epithelium and stroma was normal in 86.7 percent and 87.3 percent, respectively. In type 1 diabetic patients there was a predominance of endothelial morphological alterations (73.3 percent), polymegethism and pleomorphism (73.3 percent and 56.7 percent, respectively) and the lowest cell density (2 222.76 cells /mm2). Conclusions: Absence of morphological alterations of the corneal epithelium and stroma, as well as the presence of polymegethism and pleomorphism were the most common findings(AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Contagem de Células/métodos , Córnea/anormalidades , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 2/etiologia , Epidemiologia Descritiva , Microscopia Confocal/métodos
10.
Biomed Res Int ; 2020: 1648264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099842

RESUMO

The increase in type 1 diabetes mellitus (T1DM) incidence in children is worrying and not yet fully explored. It is suggested that probably air pollution exposure could contribute to the development of T1DM. The aim of the study was to investigate the relationship between the concentration of gaseous pollutants including, nitrogen dioxide (NO2), nitric oxides (NOx), sulphur dioxide (SO2), carbon monoxide (CO), and particulate matter (PM) in the air, and the number of new cases of T1DM in children. The number of new cases of T1DM was obtained from the Clinic of Paediatrics, Diabetology, and Endocrinology, Medical University of Gdansk. The number of children of 0-18 years old in Pomeranian Voivodeship was acquired from the Statistical Yearbook. The concentrations of PM10 absorbance, NO2, NOx, SO2, and CO were measured at 41 measuring posts, between 1 January 2015 and 31 December 2016. It was detected that the average annual concentration of PM10 was higher than the value acceptable to the WHO. Furthermore, the average 24-hour concentration of PM10 was 92 µg/m3 and was higher compared to the acceptable value of 50 µg/m3 (acc. to EU and WHO). Moreover, the number of new cases of T1DM showed a correlation with the annual average concentration of PM10 (ß = 2.396, p < 0.001), SO2 (ß = 2.294, p < 0.001), and CO (ß = 2.452, p < 0.001). High exposure to gaseous pollutants and particulate matter in ambient air may be one of the factors contributing to the risk of developing T1DM in children. Therefore, it is important to take action to decrease air pollutant emissions in Poland. It is crucial to gradually but consistently eliminate the use of solid fuels, such as coal and wood in households, in favour of natural gas and electricity. The development of new technologies to improve air quality, such as "best available techniques" (BAT) or renewable energy sources (water, wind, and solar generation) is of critical importance as well.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Diabetes Mellitus Tipo 1/epidemiologia , Exposição Ambiental/efeitos adversos , Material Particulado/administração & dosagem , Adolescente , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/etiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Polônia/epidemiologia
12.
Lancet Diabetes Endocrinol ; 8(3): 226-238, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31999944

RESUMO

Type 1 diabetes is a chronic, immune-mediated disease characterised by the destruction of insulin-producing cells. Standardised registry data show that type 1 diabetes incidence has increased 3-4% over the past three decades, supporting the role of environmental factors. Although several factors have been associated with type 1 diabetes, none of the associations are of a magnitude that could explain the rapid increase in incidence alone. Moreover, evidence of changing prevalence of these exposures over time is insufficient. Multiple factors could simultaneously explain the changing type 1 diabetes incidence, or the magnitude of observed associations could have been underestimated because of exposure measurement error, or the mismodelling of complex exposure-time-response relationships. The identification of environmental factors influencing the risk of type 1 diabetes and increased understanding of the cause at the individual level, regardless of the ability to explain the changing incidence at the population level, is important because of the implications for prevention.


Assuntos
Autoimunidade/imunologia , Diabetes Mellitus Tipo 1/epidemiologia , Exposição Ambiental/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Diabetes Mellitus Tipo 1/etiologia , Feminino , Humanos , Incidência , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Prognóstico , Fatores de Risco
13.
Diabetes Care ; 43(3): 580-587, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31937610

RESUMO

OBJECTIVE: Sustained excess BMI increases the risk of type 1 diabetes (T1D) in autoantibody-positive relatives without diabetes of patients. We tested whether elevated BMI also accelerates the progression of islet autoimmunity before T1D diagnosis. RESEARCH DESIGN AND METHODS: We studied 706 single autoantibody-positive pediatric TrialNet participants (ages 1.6-18.6 years at baseline). Cumulative excess BMI (ceBMI) was calculated for each participant based on longitudinally accumulated BMI ≥85th age- and sex-adjusted percentile. Recursive partitioning analysis and multivariable modeling defined the age cut point differentiating the risk for progression to multiple positive autoantibodies. RESULTS: At baseline, 175 children (25%) had a BMI ≥85th percentile. ceBMI range was -9.2 to 15.6 kg/m2 (median -1.91), with ceBMI ≥0 kg/m2 corresponding to persistently elevated BMI ≥85th percentile. Younger age increased the progression to multiple autoantibodies, with age cutoff of 9 years defined by recursive partitioning analysis. Although ceBMI was not significantly associated with progression from single to multiple autoantibodies overall, there was an interaction with ceBMI ≥0 kg/m2, age, and HLA (P = 0.009). Among children ≥9 years old without HLA DR3-DQ2 and DR4-DQ8, ceBMI ≥0 kg/m2 increased the rate of progression from single to multiple positive autoantibodies (hazard ratio 7.32, P = 0.004) and conferred a risk similar to that in those with T1D-associated HLA haplotypes. In participants <9 years old, the effect of ceBMI on progression to multiple autoantibodies was not significant regardless of HLA type. CONCLUSIONS: These data support that elevated BMI may exacerbate islet autoimmunity prior to clinical T1D, particularly in children with lower risk based on age and HLA. Interventions to maintain normal BMI may prevent or delay the progression of islet autoimmunity.


Assuntos
Autoimunidade , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/etiologia , Ilhotas Pancreáticas/imunologia , Obesidade Pediátrica/complicações , Obesidade Pediátrica/imunologia , Adolescente , Adulto , Autoanticorpos/sangue , Autoanticorpos/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Progressão da Doença , Feminino , Haplótipos , Humanos , Lactente , Ilhotas Pancreáticas/patologia , Masculino , Pessoa de Meia-Idade , Obesidade Pediátrica/epidemiologia , Fatores de Risco , Adulto Jovem
14.
Diabetes Care ; 43(3): 556-562, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31896601

RESUMO

OBJECTIVE: This study investigates two-phase growth patterns in early life and their association with development of islet autoimmunity (IA) and type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The Environmental Determinants of Diabetes in the Young (TEDDY) study followed 7,522 genetically high-risk children in Sweden, Finland, Germany, and the U.S. from birth for a median of 9.0 years (interquartile range 5.7-10.6) with available growth data. Of these, 761 (10.1%) children developed IA and 290 (3.9%) children were diagnosed with T1D. Bayesian two-phase piecewise linear mixed models with a random change point were used to estimate children's individual growth trajectories. Cox proportional hazards models were used to assess the effects of associated growth parameters on the risks of IA and progression to T1D. RESULTS: A higher rate of weight gain in infancy was associated with increased IA risk (hazard ratio [HR] 1.09 [95% CI 1.02, 1.17] per 1 kg/year). A height growth pattern with a lower rate in infancy (HR 0.79 [95% CI 0.70, 0.90] per 1 cm/year), higher rate in early childhood (HR 1.48 [95% CI 1.22, 1.79] per 1 cm/year), and younger age at the phase transition (HR 0.76 [95% CI 0.58, 0.99] per 1 month) was associated with increased risk of progression from IA to T1D. A higher rate of weight gain in early childhood was associated with increased risk of progression from IA to T1D (HR 2.57 [95% CI 1.34, 4.91] per 1 kg/year) in children with first-appearing GAD autoantibody only. CONCLUSIONS: Growth patterns in early life better clarify how specific growth phases are associated with the development of T1D.


Assuntos
Trajetória do Peso do Corpo , Desenvolvimento Infantil/fisiologia , Diabetes Mellitus Tipo 1/etiologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/patologia , Progressão da Doença , Feminino , Finlândia/epidemiologia , Predisposição Genética para Doença , Alemanha/epidemiologia , Gráficos de Crescimento , Humanos , Lactente , Masculino , Estudos Prospectivos , Fatores de Risco , Suécia/epidemiologia , Estados Unidos/epidemiologia
15.
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
16.
Curr Diabetes Rev ; 16(6): 641-648, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31654516

RESUMO

INTRODUCTION: The typical factors precipitating diabetic ketoacidosis (DKA) include infections (30%), cessation of antidiabetic medication (20%), and a new diagnosis of diabetes (25%). The etiology remains unknown in 25% of cases. Less frequent causes cited in the literature include severe thyrotoxicosis and, infrequently, pericarditis. Few publications have described the role of human T lymphotropic virus type 1 (HTLV-1) in endocrine and metabolic disorders. Based on a clinical case associated with several endocrine and metabolic disorders, we suggest a potential role for HTLV-1, an endemic virus in the Amazonian area, and review the literature concerning the role of this virus in thyroiditis, pericarditis and diabetes mellitus. CASE REPORT: A fifty-year-old Surinamese woman without any medical history was admitted for diabetic ketoacidosis. No specific anti-pancreatic autoimmunity was observed, and the C-peptide level was low, indicating atypical type-1 diabetes mellitus. DKA was associated with thyrotoxicosis in the context of thyroiditis and complicated by nonbacterial pericarditis and a Staphylococcus aureus subcutaneous abscess. The patient was infected with HTLV-1. CONCLUSION: To our knowledge, this uncommon association is described for the first time. Few studies have analyzed the implications of HTLV-1 infection in thyroiditis and diabetes mellitus. We did not find any reports describing the association of pericarditis with HTLV-1 infection. Additional studies are necessary to understand the role of HTLV-1 in endocrine and cardiac disorders.


Assuntos
Abscesso/etiologia , Infecções por Deltaretrovirus/complicações , Diabetes Mellitus Tipo 1/etiologia , Cetoacidose Diabética/etiologia , Pericardite/etiologia , Tireotoxicose/etiologia , Abscesso/imunologia , Abscesso/microbiologia , Doença Aguda , Infecções por Deltaretrovirus/virologia , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/virologia , Cetoacidose Diabética/imunologia , Cetoacidose Diabética/terapia , Cetoacidose Diabética/virologia , Feminino , Vírus Linfotrópico T Tipo 1 Humano/isolamento & purificação , Humanos , Imunocompetência , Pessoa de Meia-Idade , Pericardite/virologia , Infecções Cutâneas Estafilocócicas/etiologia , Infecções Cutâneas Estafilocócicas/imunologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Suriname , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Tireoidite/virologia , Tireotoxicose/virologia
17.
Acta Diabetol ; 57(4): 503-511, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31520124

RESUMO

Little is known about the human islet life span, and beta-cell neogenesis is generally considered rare in adults. However, based on available data on beta-cell proliferation, calculations can be made suggesting that the dynamics of the endocrine pancreas is considerable even during adulthood, with islet neogenesis and a sustained increase in size of already formed islets. Islet-associated hemorrhages, frequently observed in most mammals including humans, could account for a considerable loss of islet parenchyma balancing the constant beta-cell proliferation. Notably, in subjects with type 1 diabetes, periductal accumulation of leukocytes and fibrosis is frequently observed, findings that are likely to negatively affect islet neogenesis from endocrine progenitor cells present in the periductal area. Impaired neogenesis would disrupt the balance, result in loss of islet mass, and eventually lead to beta-cell deficiency and compromised glucose metabolism, with increased islet workload and blood perfusion of remaining islets. These changes would impose initiation of a vicious circle further increasing the frequency of vascular events and hemorrhages within remaining islets until the patient eventually loses all beta-cells and becomes c-peptide negative.


Assuntos
Diabetes Mellitus Tipo 1/etiologia , Ilhotas Pancreáticas/fisiologia , Adulto , Animais , Proliferação de Células , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Humanos , Células Secretoras de Insulina/fisiologia , Ilhotas Pancreáticas/metabolismo , Células-Tronco/fisiologia
18.
Cell Mol Life Sci ; 77(1): 179-194, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31172216

RESUMO

It has been suggested that the persistence of coxsackieviruses-B (CV-B) in pancreatic beta cells plays a role in the pathogenesis of type 1 diabetes (T1D). Yet, immunological effectors, especially natural killer (NK) cells, are supposed to clear virus-infected cells. Therefore, an evaluation of the response of NK cells to pancreatic beta cells persistently infected with CV-B4 was conducted. A persistent CV-B4 infection was established in 1.1B4 pancreatic beta cells. Infectious particles were found in supernatants throughout the culture period. The proportion of cells containing viral protein VP1 was low (< 5%), although a large proportion of cells harbored viral RNA (around 50%), whilst cell viability was preserved. HLA class I cell surface expression was downregulated in persistently infected cultures, but HLA class I mRNA levels were unchanged in comparison with mock-infected cells. The cytolytic activities of IL-2-activated non-adherent peripheral blood mononuclear cells (PBMCs) and of NK cells were higher towards persistently infected cells than towards mock-infected cells, as assessed by an LDH release assay. Impaired cytolytic activity of IL-2-activated non-adherent PBMCs from patients with T1D towards infected beta cells was observed. In conclusion, pancreatic beta cells persistently infected with CV-B4 can be lysed by NK cells, implying that impaired cytolytic activity of these effector cells may play a role in the persistence of CV-B in the host and thus in the viral pathogenesis of T1D.


Assuntos
Infecções por Coxsackievirus/complicações , Diabetes Mellitus Tipo 1/virologia , Enterovirus Humano B/imunologia , Células Secretoras de Insulina/virologia , Células Matadoras Naturais/imunologia , Adulto , Linhagem Celular , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/virologia , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/imunologia , Humanos , Imunidade Celular , Células Secretoras de Insulina/imunologia , Pessoa de Meia-Idade
19.
Front Immunol ; 10: 2811, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31849983

RESUMO

Type 1 diabetes (T1D) is prompted by defective immunological tolerance, an event in which dendritic cells (DCs) are crucial as immune response orchestrators. In fact, they contribute to maintaining tolerance to self-antigens, but they can also prompt an immunogenic response against them, leading to autoimmunity. Countless factors can potentially impact on the proper functionality of the DCs, which range from altered subset distribution, impaired phagocytic function to abnormal gene expression. Moreover, in T1D, metabolic dysregulation could impair DC functions as well. Indeed, since T1D clinical course is likely to be more aggressive in children and adolescents and entails severe dysglycemia, the aim of this study was to analyze circulating DCs subpopulations in pediatric T1D at different stages, as well as to characterize their phagocytosis ability and tolerance induction potential. Thus, pediatric patients newly diagnosed with T1D, with established disease and control subjects were recruited. Firstly, DCs subsets from peripheral blood were found quantitatively altered during the first year of disease, but recovered in the second year of progression. Secondly, to study the tolerogenic functionality of DCs, liposomes with phosphatidylserine (PS) were designed to mimic apoptotic beta cells, which are able to induce tolerance, as previously demonstrated by our group in DCs from adult patients with T1D. In this study, monocyte-derived DCs from pediatric patients with T1D and control subjects were assessed in terms of PS-liposomes capture kinetics, and transcriptional and phenotypic changes. DCs from pediatric patients with T1D were found to phagocyte PS-liposomes more slowly and less efficiently than DCs from control subjects, inversely correlating with disease evolution. Nonetheless, the transcription of PS receptors and immunoregulatory genes, cytokine profile, and membrane expression of immunological markers in DCs was consistent with tolerogenic potential after PS-liposomes phagocytosis. In conclusion, T1D progression in childhood entails altered peripheral blood DCs subsets, as well as impaired DCs phagocytosis, although tolerance induction could still function optimally. Therefore, this study provides useful data for patient follow-up and stratification in immunotherapy clinical trials.


Assuntos
Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/metabolismo , Suscetibilidade a Doenças , Tolerância Imunológica , Fagocitose/imunologia , Adolescente , Autoantígenos/imunologia , Autoimunidade , Biomarcadores , Plasticidade Celular/imunologia , Criança , Pré-Escolar , Citocinas/metabolismo , Diabetes Mellitus Tipo 1/diagnóstico , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunomodulação , Masculino , Fagocitose/genética
20.
Curr Diab Rep ; 19(11): 124, 2019 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712908

RESUMO

BACKGROUND: Caesarean section (CS) has been associated with an increased risk of type 1 diabetes (T1D). The lack of exposure to maternal vaginal and anal microbiome and bypassing the labor process often observed in elective CS may affect neonatal immune system development. This study aims to summarize the effects of elective and non-elective CS on T1D risk in the offspring. METHODS: A systematic literature search was conducted online for publications providing data on elective and non-elective CS with T1D diagnosis in children and young adults, followed by a meta-analysis from selected studies. Newcastle-Ottawa Scale and GRADEpro tool were applied for quality analysis. RESULTS: Nine observational studies comprising over 5 million individuals fulfilled the inclusion criteria. Crude OR estimates showed a 12% increased T1D risk from elective CS compared to vaginal delivery with significant heterogeneity. Adjusted ORs from seven studies did not show T1D risk differences from either CS category, and heterogeneity was detected between studies. Separate analysis of cohort and case-control studies reduced the heterogeneity and revealed a slight increase in T1D risk associated with elective CS in cohort studies (adjusted OR = 1.12 (1.01-1.24)), and a higher increased risk associated with non-elective CS in case-control studies (adjusted OR = 1.19 (1.06-1.34)). CONCLUSION: Summarized crude risk estimates showed a small increased T1D risk in children and young adults born through elective CS compared to vaginal delivery, but with significant heterogeneity. Adjusted risk estimates by study design indicated a slightly increased T1D risks associated with elective or non-elective CS.


Assuntos
Doenças Autoimunes/imunologia , Cesárea/efeitos adversos , Diabetes Mellitus Tipo 1/imunologia , Canal Anal/microbiologia , Parto Obstétrico , Diabetes Mellitus Tipo 1/etiologia , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Microbiota/imunologia , Estudos Observacionais como Assunto , Gravidez , Risco , Vagina/microbiologia
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