Autoimmunity does not contribute to the highly prevalent glucose metabolism disturbances in a Japanese Brazilian population.

The Japanese Brazilian population has one of the highest prevalences of diabetes worldwide. Despite being non-obese according to standard definitions, their body fat distribution is typically central. We investigated whether a subset of these subjects had autoantibodies that would suggest a slowly progressive form of type 1 diabetes. A total of 721 Japanese Brazilians (386 men) in the 30- to 60-year age group underwent clinical examination and laboratory procedures, including a 75-g oral glucose tolerance test and determinations of serum autoantibodies. Antibodies to glutamic acid decarboxylase (GADab) were determined by radioimmunoassay and to thyroglobulin (TGab) and thyroperoxidase (TPOab) by flow-cytometry assays. Mean body mass index was 25.2 +/- 3.8 kg/m2, but waist circumference was elevated according to the Asian standards. Diabetes, impaired glucose tolerance, and impaired fasting glycemia were found in 31%, 22%, and 22%, respectively, and 53% of the subjects had metabolic syndrome. Glutamic acid decarboxylase (GADab) was positive in 4.72%, TGab in 9.6%, and TPOab in 10% of the whole sample. When participants were stratified according to the presence of thyroid antibodies, similar frequencies of GADab were found in positive and negative groups. The prevalence rates of glucose metabolism disturbances did not differ between GADab positive and negative groups. Our data did not support the view that autoimmune injury could contribute to the high prevalence of diabetes seen in Japanese Brazilians, and the presence of co-morbidities included in the spectrum of metabolic syndrome favors the classification as type 2 diabetes.

Plasma adiponectin levels and incident glucose intolerance in Japanese-Brazilians: a seven-year follow-up study.

The objective of this study was to investigate whether decreased baseline adiponectin levels are an independent risk factor for development of glucose intolerance in a population-based study of Japanese-Brazilians, a group with one of the highest prevalence rates of diabetes worldwide. We examined 210 Japanese-Brazilians (97 male and 113 female, aged 56.7+/-10.1 years) with normal glucose tolerance (NGT). Plasma adiponectin, insulin, fasting and 2-h plasma glucose and lipid profile were evaluated at baseline and also at 7-year follow-up. Plasma adiponectin levels were significantly lower in glucose intolerance progressors compared with subjects who remained NGT. By increasing tertiles of adiponectin, the frequencies of subjects who progressed to glucose intolerance were 40%, 33% and 27% and the frequencies of subjects who remained NGT were 13%, 35% and 52% (chi2=15.8, p=0.001). Logistic regression analyses showed that adiponectin levels (OR for the highest versus lowest tertile: 0.31; 95% CI: 0.12-0.84, p=0.021), male sex (OR: 2.61, 95% CI: 1.21-5.65, p=0.015), fasting plasma glucose (0R: 3.05, 95% CI: 1.35-6.91, p=0.008) and waist circumference (OR: 1.04, 95% CI: 1.00-1.08, p=0.046) were independent risk factors for the progression to glucose intolerance. In conclusion, low plasma levels of adiponectin is one of several independent predictors of glucose intolerance in a Japanese-Brazilian population.

[Prevalence of immunologic markers (Anti-GAD and Anti-IA2) in first-degree relatives of patients with type I diabetes in the greater area of São Paulo]. / Prevalência dos marcadores imunológicos Anti-GAD e Anti-IA2 em parentes de primeiro grau de diabéticos do tipo I em amostra da população da Grande São Paulo.

BACKGROUND: Increasingly accurate prediction of Type I Diabetes Mellitus (DMI), based on analysis of autoantibody markers, has become possible in first-degree relatives of patients with diabetes (PDMI). These markers indicate autoimmune process against pancreatic islet beta-cells. Anti-GAD and anti-IA2 are considered predictive of DMI, whose prevalences are considerably variable in different populations studied. There are few data about the frequency of these markers on the Brazilian population. The aim of this study is determine the prevalence of positivity for anti-GAD and for anti-IA2 among DMI patients first-degree relatives (PDMI) in a sample of the Brazilian population of Great São Paulo City. METHODS: Forty-eight children and adolescents PDMI with median of age of 14.5 years (range 6.7 to 17.9 years). Anti-GAD and anti-IA2 was measured by radioassay (Kronus , USA). The cut-off limit for both antibodies was set at the 99th percentile from normal subjects serum samples (anti-GAD: n=194; Median of age=13.4 yrs; range 9.7 to 64 yrs; anti-IA2: n=71; Median of age=12.6; range 11.1-15.2 yrs). A subject was considered to be positive for anti-IA2 if specific binding exceeded the 99th among the analysis of 71 subjects. The limit to positivity was 1.72 U/ml to anti-GAD and 0.97 U/ml to anti-IA2. RESULTS: Five PDMI (10.4%) have showed positivity to anti-GAD, with significantly higher prevalence than controls (P<0.01). The anti-IA2 prevalence rate seems to be equivalent between PDMI and controls. CONCLUSION: The prevalence of anti-GAD has been more prevalent among the PDMI. No differences were observed between prevalences for anti-IA2 showed by PDMI and controls.

Prevalence of vitamin D receptor gene polymorphisms FokI and BsmI in Brazilian individuals with type 1 diabetes and their relation to beta-cell autoimmunity and to remaining beta-cell function.

The effect of the vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes (T1DM) is heterogeneous. Genetic factors may also influence the residual beta-cell function. We studied the frequency of VDR FokI (rs10735810) and BsmI (rs154410) polymorphisms in T1DM and their relationship to beta-cell autoimmunity and residual beta-cell function. We genotyped 189 T1DM (diabetes duration, 7.1 +/- 5.4 years) and 194 controls (C) by restriction length polymorphism-polymerase chain reaction. GAD65Ab, IA2Ab, ionized calcium (iCa), HbA(1c)and fasting C-peptide (FCP) were evaluated. FCP values greater than 0.6 ng/ml were considered as residual beta-cell function. The BsmI was more frequent in the C (bb plus Bb 79.1 C vs. 66.1% T1DM, p = 0.006), and the FokI polymorphism frequencies were similar between T1DM and C. We did not observe differences in pancreatic autoantibody profiles according to VDR genotypes. We observed that T1DM with f allele tended to have lower residual pancreatic beta-cell function (5.8% ff and Ff vs. 14.3% FF, p = 0.074) with similar age, diabetes duration, AAb positivity, HbA(1c), and iCa. Age at diagnosis of T1DM with BsmI polymorphism tended to be greater (10.7 +/- 4.9 bb and Bb vs. 9.3 +/- 4.5 years BB, p = 0.06). In conclusion, the results of this study showed no relationship between VDR polymorphisms and beta-cell autoimmunity; however we observed a relationship with age and remaining beta-cell function in Brazilian individuals with T1DM. These data may contribute to understanding the heterogeneous relationship between genetic markers and clinical features observed in this disease.

Prevalência dos marcadores imunológicos Anti-GAD e Anti-IA2 em parentes de primeiro grau de diabéticos do tipo 1 em amostra da população da Grande São Paulo / Prevalence of immunological markers (Anti-GAD and Anti-IA2) in first-degree relatives of patients with type 1 diabetes in Great São Paulo City

O diabetes tipo 1A (DM1) é causado por mecanismo auto-imune contra células beta em indivíduos com predisposição genética. Auto-anticorpos anti-GAD e anti-IA2 são considerados importantes marcadores destas alterações, cuja prevalência variam, segundo a população estudada e história familiar. Dados sobre freqüência desses marcadores na população brasileira são escassos. OBJETIVOS: Avaliar a freqüência de anti-GAD e anti-IA2 em parentes de primeiro grau de portadores de DM1 (PDM1) em amostra da população da Grande São Paulo. MÉTODOS: Quarenta e oito jovens PDM1 foram recrutados junto a 36 propósitos assistidos em ambulatórios especializados em diabetes da Grande São Paulo, apresentando mediana de idade de 14,5 anos (6,7 a 17,9 anos). Os valores de referência do anti-GAD foram obtidos utilizado-se soros de 194 voluntários normais, sem antecedentes familiares de DM1, com idade de 9,7 a 64,0 anos (mediana de 13,4). Soros de 71 indivíduos normais com idade variando de 11,1 a 15,2 anos (Mi= 12,6) foram submetidos à dosagem de anti-IA2. As dosagens dos marcadores foram através do radioensaio (KRONUS®, Idaho, USA). Valores acima do 99º percentil obtido no grupo controle foram considerados positivos. RESULTADOS: O 99º percentil correspondeu ao valor 1,72 U/ml para o anti-GAD e 0,97 U/ml para o anti-IA2. Cinco indivíduos dos PDM1 (10,4 por cento) foram positivos para o anti-GAD, contra 0,5 por cento dos controles (P<0,01). Um jovem do grupo PDM1 mostrou-se positivo para o anti-IA2 (2,1 por cento), com freqüência semelhante aos controles. CONCLUSÃO: O anti-GAD mostrou maior prevalência entre os PDM1, não havendo diferença entre o PDM1 e controles quanto à freqüência de anti-IA2

Leptinemia e secreçäo pancreática em homens / Pancreatic leptin and secretion in men

Na literatura, crescem as evidências de um possível envolvimento da insulina como reguladora da síntese adipocítica de leptina. Com o objetivo de estudar as possíveis corelações entre a leptina com a secreção das células beta-pancreáticas, em homens, estudou-se 19 indivíduos jovens (idades entre 25-33 anos), saudáveis, com tolerância normal à glicose. Os indivíduos foram avaliados por vários parâmetros de composição corporal como peso. IMC, medida da relação entre a cintura e o quadril e o percentual de gordura corporal (densitometria, LUNAR-DPX). Realizou-se dosagens com o emprego de ensaios específicos de glicose, insulina, pró-insulina, peptídeo C e leptina basais e 120 min após sobrecarga com 75 g de glicose. Encontrou-se correlações (teste de Spearman) positivas entre os níveis de leptina com todas as medidas antropométricas (todas com p < 0,0001). A leptinemia correlacionou-se positivamente com os níveis de insulina basal (r = 0,67; p < 0,05), insulina 120 min (r = 0,76; p < 0,0001), pró-insulina basal (r = 0,68; p < 0,0005), pró-insulina 120 min (r = 0,71; p < 0,0001), peptídeo C basal (r = 0,66; p < 0,005) e peptídeo C 120 min (r = 0,66; p < 0,005). Em resumo, encontramos uma associação entre os níveis circulantes de leptina com os vários produtos de secreção das células b-pancreáticas, em homens, reforçando o conceito da existência de um eixo hormonal entre o adipócito e as ilhotas pancreáticas.

Auto Anticorpos anti-ilhota e anti-insulina em diabéticos do tipo 1 de diagnóstico recente e parentes de primeiro grau brasileiros / Autoantibodies anti-islets and anti-insulin in patients with recently dianosed type I diabetes and in Brazilian first degree relatives

Os autoanticorpos contra as células pancreáticas têm sido utilizados para caracterizar e determinar o risco de evoluçao para o diabetes mellitus do tipo 1 (DM1) autoimune. No entanto, a maioria desses estudos foram realizados em populaçoes norte-americanas, européias ou asiáticas. No presente estudo foram avaliadas, em brasileiros, as prevalências dos autoanticorpos anti-ilhota (ICA) e anti-insulina (IAA) em normais (N), DM1 com início recente - menos de 6 meses de diagnóstico (DM1ir) e parentes de primeiro grau de DM1, nao diabéticas (PGDM1). Os métodos utilizados foram: imunohistoquímica (imunoperoxidade-proteína A) para os ICA e radioensaio supersensível para os IAA. A prevalência dos ICA isoladamente foi: N= 2,1 por cento (1/48), PGDM1= 5,6 por cento (3/54), DM1ir= 68 por cento (50/74) e dos IAA: N= 0 por cento (0/17), PGDM1= 18,7 por cento (27/144), DM1ir= 47,5 por cento (29/61); e de ambos. ICA+IAA, foi: N= 0 por cento (0/17), PGDM1= 1,8 por cento (1/54), DM1ir= 36 por cento (9/53). A positividade dos ICA (p<0,001), dos IAA (p<0,001) e de ambos (p<0,001) foi mais prevalente nos DM1ir. OS ICA foram mais prevalentes nos DM1ir entre 5 e 15 anos do que naqueles com idade superior a 30 anos por ocasiao do diagnóstico (p=0,003). Há uma correlaçao inversa (rS= -0,42, p<0,001) entre os níveis de IAA e a idade ao diagnóstico. Os níveis de IAA nos DM1ir (165,9+33,7 nU/ml; X+EPM) foram maiores do que nos N (22,3+2,5 nU/ml;p<0,001) e nos PGDM1 (508,7 nU/ml; p=0,03). Esses resultados mostram uma alta prevalência de autoimunidade nos DM1 da populaçao brasileira. A prevalência dos ICA e a distribuiçao dos IAA entre as faixas etárias dos DM1ir foram semelhantes às encontradas em populaçoes pareadas de outros países. Assim, também no nosso meio, os ICA e os IAA podem ser utilizados para o diagnóstico do DM1 autoimune. Estudos longitudinais de crianças com ICA ou IAA positivos sao necessários no nosso país para se determinar o valor preditivo destes anticorpos para a doença manifesta.