Immunoinflammatory mediators in the pathogenesis of diabetes mellitus / Mediadores imunoinflamatórios na patogênese do diabetes mellitus

ABSTRACT Characterized as a metabolic syndrome with multiple consequences for the lives of patients, diabetes mellitus is also classified as a chronic non-communicable disease of great scope in the world. It is a complex disease, with different points of view, including the relation between inflammatory process, obesity and insulin resistance due to the performance of the various immunoinflammatory mediators - called adipokines - on glycemic homeostasis. Recent studies have precisely addressed this aspect for the development of drugs that assist in the protection of pancreatic ß cells from the damages arising from oxidative stress and inflammatory process, in order to control the hyperglycemic picture, which is characteristic of diabetes mellitus.

RESUMO Caracterizado como uma síndrome metabólica de múltiplas consequências para a vida de seus portadores, o diabetes mellitus é também classificado como uma doença crônica não transmissível de grande abrangência no mundo. Trata-se de uma doença complexa, com diversos pontos de vista, dentre eles a relação entre processo inflamatório, obesidade e resistência à ação da insulina, devido à atuação dos diversos mediadores imunoinflamatórios, chamados de adipocinas, sobre a homeostase glicêmica. Recentes estudos têm abordado justamente este aspecto para o desenvolvimento de fármacos que auxiliem na proteção das células ß pancreáticas dos danos advindos do estresse oxidativo e processo inflamatório, de modo a controlar o quadro hiperglicêmico característico do diabetes mellitus.

Mucormicosis rino-órbito-cerebral de origen dental / Rhino-orbito-cerebral mucormycosis from dental origin: Case report

Resumen La mucormicosis es una infección aguda causada por hongos oportunistas pertenecientes al orden de los mucorales, que afecta principalmente a pacientes diabéticos e inmunosuprimidos. Se reporta el caso de un hombre diabético de 63 años de edad, que se extrajo una pieza dental por sus propios medios y, posteriormente, desarrolló una mucormicosis rino-órbito-cerebral con afección cutánea y palatina. La especie aislada mediante cultivos micológicos fue Rhizopus sp.

Abstract Rhino-orbito-cerebral mucormycosis from dental origin is an acute infection caused by opportunistic fungi belonging to the order of Mucorales, which affects mainly diabetic and immunocompromised patients. We report the case of a 63-year old diabetic man who performed a dental extraction on himself by his own means and subsequently developed a rhino-orbito-cerebral mucormycosis with cutaneous and palatal affection. The species isolated in the mycological culture was Rhizopus sp.

Cobertura vacinal e utilização do SUS para vacinação contra gripe e pneumonia em adultos e idosos com diabetes autorreferida, no município de São Paulo, 2003, 2008 e 2015 / Cobertura de vacunación y uso del sistema público de salud brasileño para vacunación contra gripe y neumonía en adultos y ancianos con diabetes autorreferida, en la ciudad de São Paulo, 2003, 2008 y 2015 / Vaccination coverage and use of the Brazilian Health System for vaccination against influenza and pneumonia in adults and elderly with self-reported diabetes, municipality of São Paulo, 2003, 2008 and 2015

Objetivo: estimar a cobertura vacinal contra gripe e pneumonia e a utilização do SUS para vacinação em adultos e idosos com diabetes autorreferida em São Paulo, SP, Brasil, em 2003, 2008 e 2015. Métodos: painel de estudos transversais do ISA-Capital. Resultados: entrevistaram-se 3.357, 3.271 e 4.043 pessoas em 2003, 2008 e 2015; as prevalências de diabetes mellitus foram de 5,0% (2003), 6,4% (2008) e 7,7% (2015); menos da metade das pessoas com diabetes vacinou-se contra gripe (47,2%) e pneumonia (17,9%) em 2003, com pequeno aumento em 2015 (59,2% e 26,1%, respectivamente); a maioria da população que se vacinou contra gripe e pneumonia o fez pelo SUS, 88,7% (2003) e 97,2% (2015) para gripe e 84,7% (2003) e 94,5% (2015) para pneumonia, sem diferença entre idade, sexo, escolaridade e raça. Conclusão: embora as coberturas vacinais tenham sido baixas na população com diabetes, a utilização do SUS foi elevada entre os vacinados.

Objetivo: estimar la cobertura de vacunas contra gripe y neumonía y la utilización del Sistema Único de Salud-SUS para vacunación en adultos y ancianos con diabetes autorreferida en la ciudad de São Paulo, Brasil, en 2003, 2008 y 2015. Métodos: datos del ISA-Capital. Resultados: entrevistados 3.357, 3.271 y 4.043 personas en 2003, 2008 y 2015; las prevalencias de diabetes mellitus fueron de 5,0% (2003), 6,4% (2008) y 7,7% (2015); menos de la mitad de las personas con diabetes mellitus se vacunaron contra gripe (47,2%) y neumonía (17,9%) en 2003, con un pequeño aumento en 2015 (59,2% y 26,1%, respectivamente); la mayoría de la población que se vacunó contra gripe y neumonía lo hizo a través del SUS: 88,7% (2003) y el 97,2% (2015) para la gripe y 84,7% (2003) y 94,5% (2015) para neumonía, sin diferencia entre edad, sexo, escolaridad y raza. Conclusión: Aunque las coberturas fueron bajas en la población con diabetes, la utilización del SUS fue elevada entre los vacunados.

Objective: to estimate the vaccination coverage against influenza and pneumonia and to analyze the utilization of Brazilian National Health System-SUS for vaccination in adults and elderly with self-reported diabetes in São Paulo, Brazil, in 2003, 2008 and 2015. Methods: Cross-sectional studies with data from the ISA-Capital (population-based household surveys). Results: 3,357, 3,271 and 4,043 were interviewed in 2003, 2008 and 2015; the prevalence of diabetes mellitus were 5.0% (2003), 6.4% (2008) and 7.7% (2015); fewer than half of people with diabetes, vaccinated against influenza (47.2%) and pneumonia (17.9%) in 2003, with a small increase in 2015 (59.2% and 26.1%, respectively); the majority of people who are vaccinated against influenza and pneumonia used SUS, 88.7% (2003) and 97.2% (2015) for influenza; 84.7% (2003) and 94.5% (2015) for pneumonia, without difference among age, sex, education level and ethnicity. Conclusion: despite the low vaccination coverage against influenza and pneumonia in the population with diabetes mellitus since 2003 the utilization of SUS to vaccination has been progressively expanding.

Controle glicêmico e auto percepção do grau de adesão à insulina em pacientes com diabetes tipo 1 no Brasil / glycemic control and self perception of the degree of adherence to insulin in patients with type 1 diabetes in Brazil. Guilherme de Sousa

Introdução: Apesar dos avanços no manejo do diabetes mellitus tipo 1 (DM1), 60% a 90% dos pacientes apresentam controle glicêmico inadequado e 10% a 30% relatam baixa adesão à insulina. Os objetivos dessa tese foram identificar fatores associados à elevada concentração de hemoglobina glicada (HbA1c) e à uma melhor percepção da adesão à insulina em pacientes com DM1 em dez cidades de grande porte no Brasil. Métodos: Foi realizado um estudo de corte transversal, multicêntrico, com pacientes ≥18 anos, com diagnóstico médico de DM1, atendidos em centros de saúde. Dados sócio demográficos, comportamentais, clínicos, de conhecimento sobre o diabetes e satisfação com o tratamento foram obtidos por meio de entrevistas. A HbA1c foi dosada para todos os participantes. Considerou-se controle glicêmico inadequado quando HbA1c >7,0%...

Introduction: Despite advances in managing diabetes mellitus type 1 (DM1), 60% to 90% of patients have poor glycemic control and 10% to 30% reported low adherence to insulin. The objectives of this thesis was to identify factors associated with high levels of glycated hemoglobin (HbA1c) and a better understanding of adherence to insulin in patients with type 1 diabetes in Brazil. Methods: We conducted a cross-sectional, multicenter study, with patients ≥18 years old, diagnosed with type 1 diabetes treated at health centers in 10 cities in Brazil. We obtained sociodemographic, behavioral and clinical data, knowledge about diabetes and satisfaction with treatment through interviews. We measured HbA1c for all participants. It was considered inadequate glycemic control when HbA1c >7.0%...

The macrophage migration inhibitory factor protein superfamily in obesity and wound repair

The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tautomerase (D-DT or MIF-2). MIF and D-DT, which both bind to the CD74/CD44 receptor complex, are differentially expressed in adipose tissue and have distinct roles in adipogenesis. MIF positively correlates with obesity as well as insulin resistance and contributes to adipose tissue inflammation by modulating ATM functions. D-DT, however, is negatively correlated with obesity and reverses glucose intolerance. In this review, their respective roles in adipose tissue homeostasis, adipose tissue inflammation, insulin resistance and impaired wound healing will be reviewed.

The macrophage migration inhibitory factor protein superfamily in obesity and wound repair

The rising number of obese individuals has become a major burden to the healthcare systems worldwide. Obesity includes not only the increase of adipose tissue mass but importantly also the altered cellular functions that collectively lead to a chronic state of adipose tissue inflammation, insulin resistance and impaired wound healing. Adipose tissue undergoing chronic inflammation shows altered cytokine expression and an accumulation of adipose tissue macrophages (ATM). The macrophage migration inhibitory factor (MIF) superfamily consists of MIF and the recently identified homolog D-dopachrome tautomerase (D-DT or MIF-2). MIF and D-DT, which both bind to the CD74/CD44 receptor complex, are differentially expressed in adipose tissue and have distinct roles in adipogenesis. MIF positively correlates with obesity as well as insulin resistance and contributes to adipose tissue inflammation by modulating ATM functions. D-DT, however, is negatively correlated with obesity and reverses glucose intolerance. In this review, their respective roles in adipose tissue homeostasis, adipose tissue inflammation, insulin resistance and impaired wound healing will be reviewed.

Avaliação da variabilidade da frequência cardíaca de idosos diabéticos e não diabéticos / Assessment of heart rate variability in elderly diabetic and nondiabetic patients

INTRODUÇÃO: O cenário de envelhecimento populacional e o aumento das Doenças Crônicas Não Transmissíveis (DCNT) requer o desenvolvimento e validação de métodos diagnóstico e de ferramentas não invasivas para identificação de fatores de risco e estadiamento destas doenças. Entre estes métodos evidencia-se a análise da modulação autonômica do coração por meio da Variabilidade da Frequência Cardíaca (VFC). OBJETIVO: Analisar a variabilidade da frequência cardíaca de idosos diabéticos (DM+) e não diabéticos (DM–) residentes em um município baiano; avaliar a resposta da variabilidade da frequência cardíaca na realização da manobra de levantar-se rapidamente. MÉTODOS: estudo epidemiológico transversal, de abordagem censitária. Desenvolvido com 205 idosos da zona urbana do munícipio de Aiquara-BA, após aplicação os critérios de inclusão e exclusão. Os dados da VFC foram coletados através do monitor Polar RS800CX...

INTRODUCTION: The scenario of population aging and the increase of Chronic Noncommunicable Diseases (NCDs) requires the development and validation of diagnostic methods and non-invasive tools for identification of risk factors and staging of these diseases.Among these methods, the analysis of autonomic modulation of the heart using the Heart Rate Variability (HRV) becomes evident. OBJECTIVE: To analyze the heart rate variability in diabetic (DM+) and nondiabetic (DM–) elderlies residents in a municipality of Bahia, and also to know the response of heart rate variability in performance of the quickly stand up maneuver. METHODS: cross-sectional study of censitary approach. Carried out with 205 elderlies in the urban area of the municipality of Aiquara-BA, after had applied the inclusion and exclusion criteria. HRV data were collected through the Polar RS800CX...

Diabetes autoinmune (latente) del adulto / Latent autoimmune diabetes in adults

Backgroud: Latent Autoimmune Diabetes in Adults (LADA) is the term used to describe adults who have a slowly progressive form of diabetes mellitus (DM) of autoimmune etiology, but that may be treated initially without insulin. Although it shares some immunological and genetic aspects with type 1 DM, it affects an age group that is typically affected by type 2 DM. Therefore, it could be considered an intermediate type. Diagnosis is based on clinical and laboratory criteria: age of onset, initial response to oral hypoglycemic agents and the presence of specific antibodies for diabetes. Although the definitive treatment is insulin, glitazones may be useful in early stages of the disease. Currently, its management represents a challenge for the physician, including specialists, and it is a form of DM to keep in mind.

Serological tests for the diagnosis of active tuberculosis: relevance for India.

Diagnostic tests for active tuberculosis (TB) based on the detection of antibodies (serological tests) have been commercially available for decades, although no international guidelines have recommended their use. An estimated 1.5 million serological TB tests, mainly enzyme-linked immunosorbent assays, are performed in India alone every year, mostly in the private sector. The cost of serological tests in India is conservatively estimated at US $15 million (825 million) per year. Findings from systematic reviews on the diagnostic accuracy of serological tests for both pulmonary and extra-pulmonary TB suggest that these tests are inaccurate and imprecise. A cost-effectiveness modelling study suggests that, if used as a replacement test for sputum microscopy, serology would increase costs to the Indian TB control sector approximately 4-fold and result in fewer disability-adjusted life years averted and more false-positive diagnoses. After considering all available evidence, the World Health Organization issued a strong recommendation against the use of currently available commercial serological tests for the diagnosis of TB disease. The expanding evidence base continues to demonstrate that the harms/risks of serological tests far outweigh the benefits. Greater engagement of the private sector is needed to discontinue the use of serological tests and to replace these tests with WHO-endorsed new diagnostics in India. The recent ban on import or sale of TB serological tests by the Indian health ministry is a welcome step in the right direction.

Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats.

Background & objectives: A large number of plants have been recognized to be effective in the treatment of diabetes mellitus. Persistent hyperglycaemia is associated with decreased function of immune system and cerebral ischaemia mainly due to increased oxidative stress and inflammatory response. Andrographis paniculata is a medicinal plant widely used in folk medicine for various purposes. In this study the effect of chronic administration (7 days) of methanolic extract of A. paniculata leaves was studied in rats with experimentally induced diabetes, nootropic and immunostimulant activities were evaluated. The effect of acute administration of methanolic extract of A. paniculata leaves was also studied for cerebroprotective activity. Methods: Type 2 diabetes was induced in rats by streptozotocin (STZ) (65 mg/kg) + nicotinamide (150 mg/kg). Various biochemical parameters were estimated using standard methods. Results: A significant (P<0.05) increase in cognitive function was observed in both normal and type 2 diabetic rats. Nootropic activity in terms of per cent reduction in latency period was more in type 2 diabetic rats. A significant increase in blood lymphocyte count, splenic lymphocyte count and peritoneal macrophage count was observed in both normal and type 2 diabetic rats. Immunostimulant activity was observed more in type 2 diabetic rats. The per cent decrease in cerebral infarction was more in type 2 diabetic rats when compared to normal rats. The per cent increase in superoxide dismutase (SOD) levels was more in type 2 diabetic rats. Interpretation & conclusions: The antioxidant activity of the methanolic extract of A. paniculata leaves was evident by decreased tissue malondialdehyde (MDA) levels and increased SOD levels. These properties may be responsible for the observed cerebroprotective activity. The methanolic leaf extract of A. paniculata showed significant immunostimulant, cerebroprotective and nootropic activities in normal and type 2 diabetic rats.

Salivary IgA and periodontal treatment needs in diabetic patients

Salivary IgA can serve as a first line of defense against pathogens that colonize and invade mucosal surfaces and may be protective against periodontal disease. The aim of this study was to assess salivary immunoglobulin A levels in diabetic and non-diabetic patients with different periodontal treatment needs. The Periodontal Screening & Recording (PSR) system was used to evaluate the periodontal treatment needs of 41 diabetic and 42 non-diabetic patients. Unstimulated whole saliva was collected from each patient immediately before clinical examination and stored at -20 °C until analysis. Salivary immunoglobulin A (s-IgA) levels were determined using an enzyme-linked immunosorbent assay, and values were expressed as optical density. Diabetic and non-diabetic patients were compared using clinical and laboratory data. PSR data indicated that periodontal disease was more frequent and more severe in diabetic patients. A higher prevalence of codes 3 and 4 was observed in diabetics as compared with non-diabetics (odds ratio = 2, P < 0.05). Furthermore, non-diabetic patients had more healthy sextants (code 0) than did diabetic patients. Over half of diabetic patients (∼54 percent) presented with s-IgA levels that were lower than the normal range (optical density from 0.4 nm to 0.6 nm; P < 0.05). In addition, diabetic patients showed a higher variability in s-IgA levels as compared with non-diabetic patients. In conclusion, diabetic individuals had lower s-IgA levels, more-frequent and more-severe periodontal disease, and a greater need for periodontal treatment as compared with non-diabetic patients.

IIhotas pancreáticas humanas viáveis para o transplante através do aumento da massa de células e do imunoisolamento com microcápsulas biocompatíveis / Obtention of human pancreatic islets for transplantation through an increase in cell mass and an immunoisolation with biocompatible microcapsules

O transplante de ilhotas pancreáticas humanas representa uma estratégia promissora para a cura do diabetes mellitus tipo 1 (DM1) mas a aplicação a todos os pacientes diabéticos ainda é impraticável devido à limitada disponibilidade de ilhotas ou células β e à necessidade de utilização de drogas imunossupressoras pelo paciente transplantado. O tratamento com imunossupressores após o transplante de ilhotas pode ser abolido quando se realiza o microencapsulamento das ilhotas pancreáticas. Neste trabalho investigou-se um novo biomaterial, Biodritina (alginato/sulfato de condroitina) adequado ao microencapsulamento que gelifica na presença de íons de cálcio ou bário. A biocompatibilidade das microcápsulas tem sido avaliada segundo o grau de pureza do alginato utilizado na sua confecção. Amostras de alginato comercial purificado foram analisadas, comprovando-se a presença de impurezas (polifenóis, endotoxinas, proteínas) em níveis elevados, que impedem sua aplicação clínica. Optou-se, portanto pela utilização do alginato comercial ultrapurificado nos experimentos descritos neste trabalho. Das formulações de biomateriais avaliadas, as microcápsulas de bário-Biodritina apresentaram o melhor desempenho em testes de estabilidade físico-química...

Custo-efetividade do tratamento da infecção pelo vírus da hepatite C em candidatos a transplante renal submetidos à diálise / Cost-effectiveness of hepatitis C treatment in patients on dialysis awaiting renal transplantation

O estudo tem como objetivo geral avaliar a razão de custo-utilidade do tratamento da infecção pelo vírus da hepatite C (VHC) em pacientes dialisados, candidatos a transplante renal, tendo como esquemas terapêuticos alternativos o interferon-a em monoterapia; o interferon peguilado em monoterapia; o interferon-a em terapia combinada com ribavirina e o interferon peguilado em terapia combinada com ribavirina, comparando-os com o não-tratamento. A perspectiva do estudo foi a do Sistema Único de Saúde(SUS), que também serviu de base para estimar o impacto orçamentário da estratégia de tratamento mais custo efetiva. Para o alcance dos objetivos, foi construído um modelo de Makov para simulação de custos e resultados de cada estratégia avaliada. Para subsidiar o modelo, foi realizada uma revisão de literatura, a fim de definir os estados de saúde relacionados à infecção pelo vírus da hepatite C em transplantados e a probabilidade de transição entre os estados. Medidas de utilidade foram derivadas de consultas a especialistas. Os custos foram derivados da tabela de procedimentos do SUS. Os resultados do estudo demonstraram que o tratamento da infecção pelo VHC antes do transplante renal é mais custo-efetivo que o não tratamento, apontando o interferon-a como a melhor opção. O impacto orçamentário para adoção dessa estratégia pelo SUS corresponde a 0,3 por cento do valor despendido pelo SUS com terapia renal substitutiva ao longo do ano de 2007.

Frequency Of Pancreatic Beta-Cell Autoimmunity Markers In Patients With Autoimmune Thyroid Disease / Frecuencia de marcadores de autoinmunidad beta pancreática en pacientes con enfermedad tiroidea autoinmune

A total of 305 ambulatory patients recruited at the Division of Endocrinology, Hospital de Clínicas, University of Buenos Aires, with autoimmune thyroid disease (AITD) were studied to search for associations between autoimmune thyroid disease and presence of serum markers of autoimmune diabetes mellitus. Screening for markers of pancreatic beta-cell autoimmunity was performed by radioligand binding assays (RBA) as follows: autoantibodies to glutamic acid decarboxylase (GADA) and proinsulin (PAA) were determined in all sera, whereas autoantibodies to protein tyrosine phosphatase (IA-2A) and insulin (IAA) were additionally measured in 200 sera randomly selected from the total collection. In addition, every GADA positive serum among the remaining 105 sera was systematically tested for the presence of IA-2A and IAA. In the cohort of 305 AITD patients 22 (7.2%) were previously diagnosed as type 1, type 2 or insulin-requiring type 2 diabetics. Ten of these patients presented serum marker positivity specific for β-cell autoantigens and 12 were marker negative. On the other hand, considering the majority of non-diabetic AITD patients (n=283), β-cell marker positivity was detected in 17 individuals (6.0%). The prevalence of autoimmune diabetes markers was much higher in the studied population than in the general population utilized as a control group, and GADA was the most frequent marker.

Se investigó la asociación entre enfermedad tiroidea autoinmune y la presencia de marcadores séricos de diabetes mellitus en 305 pacientes ambulatorios con enfermedad tiroidea autoinmune reclutados en la División Endocrinología. La búsqueda de marcadores de autoinmunidad contra las células beta pancreáticas se realizó por la técnica de unión de radioligandos (RBA) como se detalla a continuación: se determinaron autoanticuerpos contra la decarboxilasa del ácido glutámico (GADA) y proinsulina (PAA) en todos los sueros, mientras que los anticuerpos contra la proteína tirosina fosfatasa (IA-2A) e insulina (IAA) fueron medidos en 200 de estos sueros tomados al azar de la colección total. Además, en los restantes 105 pacientes, la presencia de IA-2A y IAA fue evaluada en todos los sueros positivos para GADA. Del grupo de 305 pacientes con enfermedad tiroidea autoinmune 22 (7.2%) fueron diagnosticados previamente como diabéticos tipo 1, tipo 2 o tipo 2 insulino-requirientes. Diez de ellos presentaron positividad para marcadores específicos de autoantígenos de célula β, en tanto 12 fueron negativos. Por otra parte, en 17 de los 283 pacientes (6.0%) con enfermedad tiroidea autoimmune y sin diagnóstico previo de diabetes, se detectó positividad para marcadores de célula β. La prevalencia de marcadores de autoinmunidad asociados a diabetes fue mayor en la población estudiada que en la población general usada como grupo control, siendo GADA el marcador más frecuente.

Glutamic acid decarboxylase antibodies are indicators of the course, but not of the onset, of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities Study

To efficiently examine the association of glutamic acid decarboxylase antibody (GADA) positivity with the onset and progression of diabetes in middle-aged adults, we performed a case-cohort study representing the ~9-year experience of 10,275 Atherosclerosis Risk in Communities Study participants, initially aged 45-64 years. Antibodies to glutamic acid decarboxylase (GAD65) were measured by radioimmunoassay in 580 incident diabetes cases and 544 non-cases. The overall weighted prevalence of GADA positivity (³1 U/mL) was 7.3 percent. Baseline risk factors, with the exception of smoking and interleukin-6 (P ú 0.02), were generally similar between GADA-positive and -negative individuals. GADA positivity did not predict incident diabetes in multiply adjusted (HR = 1.04; 95 percentCI = 0.55, 1.96) proportional hazard analyses. However, a small non-significant adjusted risk (HR = 1.29; 95 percentCI = 0.58, 2.88) was seen for those in the highest tertile (³2.38 U/mL) of positivity. GADA-positive and GADA-negative non-diabetic individuals had similar risk profiles for diabetes, with central obesity and elevated inflammation markers, aside from glucose, being the main predictors. Among diabetes cases at study's end, progression to insulin treatment increased monotonically as a function of baseline GADA level. Overall, being GADA positive increased risk of progression to insulin use almost 10 times (HR = 9.9; 95 percentCI = 3.4, 28.5). In conclusion, in initially non-diabetic middle-aged adults, GADA positivity did not increase diabetes risk, and the overall baseline profile of risk factors was similar for positive and negative individuals. Among middle-aged adults, with the possible exception of those with the highest GADA levels, autoimmune pathophysiology reflected by GADA may become clinically relevant only after diabetes onset.

Latent autoimmune diabetes in adults (LADA): usefulness of anti-GAD antibody titers and benefit of early insulinization

OBJECTIVE: To determine the clinical and laboratory parameters and the progression to insulin requirement in two groups of LADA patients separated according to GADA titers, and to evaluate the benefit of early insulinization in patients at high risk of premature beta-cell failure (high GADA titers). METHODS: Among the diabetic adults seen at our service and screened for GADA at diagnosis, 54 were diagnosed with LADA and classified as having low (> 1 U/ml and < 17.2 U/ml) or high (> 17.2 U/ml) GADA titers. Fifty-four patients with type 2 diabetes (GADA-) were selected for comparison. In addition, 24 patients who had GADA titers > 20 U/ml and who were not initially insulinized were compared to 16 patients who were insulinized at diagnosis. RESULTS: Insulin resistance was higher in the GADA- group, followed by patients with low GADA titers. BMI and the frequency of arterial hypertension, elevated triglycerides and reduced HDL cholesterol were lower in the high GADA+ group, with no difference between the GADA- or low GADA+ groups. The high GADA+ group showed a greater reduction and lower levels of C-peptide and required insulin earlier during follow-up. Patients with GADA titers > 20 U/ml and insulinized early presented no significant variation in C-peptide levels, had better glycemic control and required a lower insulin dose than patients who were insulinized later. CONCLUSION: We agree that patients with LADA should be differentiated on the basis of GADA titers and that patients with GADA titers > 20 U/ml benefit from early insulinization.

OBJETIVO: Determinar os parametros clínicos e laboratoriais e a progressão para a necessidade de insulina em dois grupos de pacientes com LADA, divididos de acordo com os títulos de GADA, e avaliar o benefício da insulinização precoce naqueles com risco elevado de falência prematura das células beta (títulos altos de GADA). MÉTODOS: Dentre os pacientes adultos com diabetes (DM) seguidos em nosso serviço e rastreados para GADA no diagnóstico, 54 foram diagnosticados com LADA e classificados como tendo títulos de GADA baixos (> 1 U/ml e < 17,2 U/ml) ou altos (> 17,2 U/ml). A comparação foi feita com 54 pacientes selecionados com DM tipo 2 (GADA-). Além disso, 24 pacientes com títulos de GADA > 20 U/ml, mas que não foram insulinizados no início, foram comparados com 16 outros que foram insulinizados desde o diagnóstico. RESULTADOS: A resistência à insulina foi maior no grupo GADA-, seguidos por aqueles com títulos baixos de GADA. O IMC, a frequência de hipertensão arterial, os triglicérides elevados e o HDL-colesterol reduzido foram menores no grupo com títulos elevados de GADA, sem diferença entre os GADA- ou com baixos títulos de GADA. O grupo com títulos elevados de GADA mostrou uma redução maior e menores níveis de peptídeo C, tendo requerido insulina mais precocemente durante o seguimento. Pacientes com títulos de GADA > 20 U/ml e precocemente insulinizados não apresentaram variações significantes nos níveis de peptídeo C, tiveram melhor controle glicêmico e requereram doses mais baixas de insulina do que aqueles que foram insulinizados mais tardiamente. CONCLUSÃO: Nós concordamos que pacientes com LADA devem ser diferenciados com base nos títulos de GADA e que aqueles com títulos > 20 U/ml beneficiam-se de insulinização precoce.

Diabetes mellitus tipo 1: multifatores que conferem suscetibilidade à patogenia auto-imune / Type 1 diabetes mellitus: multifactors that confer susceptibility to the autoimmune pathogenesis

Objetivos: revisar dados de literatura concernentes aos fatores que conferem sustibilidade à patogenia auto-imune do diabetes mellitus tipo 1. Fonte de dados: revisão de artigos especializados no assunto publicados em banco de dados nacionais internacionais (scielo, lilacs e pubmed). Síntese de dados: a etiopatogenia do diabetes mellitus tipo 1 está associada a fatores inflamatórios, genéticos e ambientais. Nesta revisão, abordamos o papel da auto-imunidade humoral e celular que culmina com a disfunção das células-beta produtoras de insulina e anti-ácido glutâmico descarboxilase é uma característica importante nesta patologia. Os diversos fatores genéticos associados ao deflagramento do diabetes de mellitus tipo 1, sobretudo os associados ao sistema de antígenos leucocitários humanos, acabam por potencializar a apresentação de antígenos das ilhotas para o sistema imune. Por fim, fatores ambientais como exposição viral também contribuem para a quebra de tolerância imunológica observada nesses pacientes. Conclusões: o diabetes mellitus tipo 1 é uma entidade de etiopatogenia altamente complexa. Diversos fatores genéticos e ambientais potencializam os mecanismos de auto-imunidade humoral e celular que levam à insulite. O risco de hipoglicemia severa observada com o tratamento insulinico e as e as complicações crônicas do diabetes mellitus tipo 1 justificam pesquisas contínuas em relação à etiopatogenia desta entidade, o que contribuirá para abordagens terapêuticas mais eficazes.

Soroprevalência da doença celíaca em crianças e adolescentes com diabetes melito tipo 1 / Serum prevalence of celiac disease in children and adolescents with type 1 diabetes mellitus

OBJETIVO: A associação de doença celíaca e diabetes melito já é conhecida há várias décadas. Pode ser encontrada em uma grande proporção de pacientes diabéticos, que geralmente são assintomáticos. O objetivo do estudo foi avaliar a soroprevalência da doença celíaca em crianças e adolescentes com diabetes melito tipo 1. MÉTODOS: Através de um estudo transversal, realizou-se triagem sorológica com anticorpo IgA antitransglutaminase humana em 354 crianças e adolescentes diabéticos, atendidos em ambulatórios de endocrinologia pediátrica de Recife, Pernambuco, no período de janeiro a junho de 2004. RESULTADOS: O antitransglutaminase humana foi positivo em 37/354 pacientes, resultando em soroprevalência de 10,5 por cento (IC95 por cento 7,6-14,2 por cento). Dentre os pacientes soropositivos, houve predomínio do sexo masculino (56,8 por cento) em relação ao feminino (43,2 por cento), porém sem significância estatística. O anticorpo antiendomísio foi realizado nos pacientes com antitransglutaminase humana positivo, sendo negativo em 14/37 (37,8 por cento) e positivo em 22/37 (59,5 por cento). CONCLUSÕES: A soroprevalência da doença celíaca em crianças e adolescentes diabéticos encontrada em Pernambuco é elevada, sendo comparável à observada em estudos da América do Norte e Europa e menor do que na Africa, sugerindo que a triagem sorológica para doença celíaca seja realizada em todas as crianças e adolescentes com diabetes melito tipo 1.