Maria Fernanda Vanti Macedo Paulino

Family-based association of HLA class II alleles and haplotypes with type I diabetes in Brazilians reveals some characteristics of a highly diversified population.

The association of HLA class II haplotypes with type I diabetes was analyzed in 56 Southeastern Brazilian families using affected family-based controls (AFBAC) method. DRB1-DQA1-DQB1 alleles were determined by polymerase chain reaction/sequence-specific primer genotyping. This study first revealed the great haplotype diversity of Brazilians (65 different haplotypes even with incomplete DRB1 subtyping), probably due to the admixture of Africans genes with European and Amerindian genes in this population. The results revealed increased frequencies of the DRB1*03-DQA1*0501-DQB1*02 and DRB1*0401-DQA1*03-DQB1*0302 haplotypes in the patient group The highest risk for type I diabetes was associated with the heterozygote DRB1*03/*04 genotype as largely reported, and DRB1*03/X and DRB1*04/Y genotypes conferred a significant, but much lower disease risk. Protection from type I diabetes revealed some peculiarities in Southeastern Brazilians: a lack of significant protecting effect of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype, and an apparent protection conferred by the DRB1*13-DQB1*0301, DRB1*11-DQB1*0301, and DRB1*01-DQB1*0501 two-locus haplotypes. The risk to type I diabetes in the highly diversified Southeastern Brazilians evidenced specific information to the prediction of the disease in this region of the country.

Pubertal growth and final height in 40 patients with type 1 diabetes mellitus

OBJECTIVE Type 1 diabetes mellitus (DM1), the most important chronic endocrine-metabolic disease in children and adolescents, may lead to delayed growth and puberty. In this study we analyzed the influence of DM1 on growth spurt and puberty of patients whose onset of the disease was before or at the beginning of this phase. PATIENTS AND METHODS Data from 40 patients, 25 females, who had attained final height were retrospectively obtained, including duration of disease, patients height and weight SDS at each consultation, parental target height, yearly growth velocities (GV), peak of growth spurt, duration of puberty, magnitude of growth spurt and glycated hemoglobin (HbA1C) levels. RESULTS 37 patients had an adequate final height to parental target height, and only 3 were below the lower limit. There was no significant association among the variables and the appropriate final height to the target height, except for GV on growth spurt, when it was lower than or equal to 6 cm/year. The age of onset of DM1 and the age of peak of growth spurt was similar to previously data reported; regarding the age of the onset of puberty, there was no delay. However, the magnitude of the growth spurt and the peak of GV were lower. According to HbA1C levels, all patients exhibited a bad chronic control of DM1. CONCLUSIONS In this group of inadequately controlled patients, the final height was lower than expected when compared to the height at onset of DM1, probably due to a slow GV during puberty, which however had no influence on the final height to parental target height.

Clinical and laboratory profile of pediatric and adolescent patients with type 1 diabetes

OBJECTIVE To evaluate clinical and laboratory profiles of patients with type 1 diabetes mellitus in three public hospitals in São Paulo, Brazil, since type 1 diabetes mellitus is a chronic illness that occurs mainly in the pediatric age group in the Brazilian population. METHODS Cross-sectional study with patients followed up in reference centers in São José do Rio Preto (FAMERP), Campinas (UNICAMP) and São Paulo (Conjunto Hospitalar do Mandaqui). Data about gender, age, diabetes duration, daily insulin dose, number of daily insulin injections, and glycosylated hemoglobin (HbA1c) were analyzed. RESULTS Two hundred and thirty-nine patients (131 females) were evaluated; mean age was 13.1+/-4.7 years and mean diabetes duration was 6.6+/-4.2 years. Daily insulin doses ranged from 0.1 to 1.78 units/kg/day (0.88+/-0.28), and 180 (74.7%) patients had two daily injections. HbA1c ranged from 4.6 to 17.9% (10.0+/-2.3%). CONCLUSIONS Although the hospitals included in this study are excellence centers for the follow-up of patients with diabetes in three municipalities in the state of São Paulo, one of the most developed states in Brazil, blood glucose control evaluated according to HbA1c was not adequate. Findings confirm that, despite the efforts of all the professionals involved, great challenges still lie ahead.

Perfil clínico e laboratorial de pacientes pediátricos e adolescentes com diabetes tipo 1

OBJECTIVE: To evaluate clinical and laboratory profiles of patients with type 1 diabetes mellitus in three public hospitals in Sao Paulo, Brazil, since type 1 diabetes mellitus is a chronic illness that occurs mainly in the pediatric age group in the Brazilian population. METHODS: Cross-sectional study with patients followed up in reference centers in Sao Jose do Rio Preto (FAMERP), Campinas (UNICAMP) and Sao Paulo (Conjunto Hospitalar do Mandaqui). Data about gender, age, diabetes duration, daily insulin dose, number of daily insulin injections, and glycosylated hemoglobin (HbA1c) were analyzed. RESULTS: Two hundred and thirty-nine patients (131 females) were evaluated; mean age was 13.1±4.7 years and mean diabetes duration was 6.6±4.2 years. Daily insulin doses ranged from 0.1 to 1.78 units/kg/day (0.88±0.28), and 180 (74.7%) patients had two daily injections. HbA1c ranged from 4.6 to 17.9% (10.0±2.3%). CONCLUSIONS: Although the hospitals included in this study are excellence centers for the follow-up of patients with diabetes in three municipalities in the state of Sao Paulo, one of the most developed states in Brazil, blood glucose control evaluated according to HbA1c was not adequate. Findings confirm that, despite the efforts of all the professionals involved, great challenges still lie ahead.

Prevalência e aspectos clínicos da associação de diabetes melito tipo 1 e doença celíaca

OBJECTIVES: To estimate the prevalence of type 1 diabetes mellitus (DM1) and celiac disease association and to verify the existence of celiac disease symptoms, as well as the occurrence of other autoimmune diseases among the patients, their first-degree relatives and the possible influences of celiac disease in diabetes control. METHODS: It was done a cross-sectional study with 195 patients that answered a questionnaire about gastrointestinal symptoms and the occurrence of autoimmune diseases in their first-degree relatives. IgA was measured and antiendomysial antibody (EMA) was screened. The patients with positive EMA were submitted to intestinal biopsy. Those with celiac disease confirmed by biopsy (case group) were paired with DM1 patients without celiac disease (control group) according to age on diabetes diagnosis, diabetes duration and gender. RESULTS: EMA was positive in nine patients. In seven of them the biopsy has confirmed celiac disease (4.0%). Comparing the cases with controls, the gastrointestinal symptoms were significantly more frequent in the first group, but there was no difference between the groups regarding to the occurrence of autoimmune disease among the first-degree relatives and regarding to the control of diabetes (z weight, z height, insulin dose, HbA1c). CONCLUSIONS: The prevalence found was 4.0%. This sample of celiac patients showed a predominance of gastrointestinal symptoms, although the celiac disease did not influence the diabetes control.

Crescimento e composição corporal de crianças com diabetes mellitus tipo 1

OBJECTIVE: To evaluate the growth and body composition of pre-pubertal diabetic children, and to check for influence of the age of diabetes onset and length, sex, insulin requirement and glycosylated hemoglobin. PATIENTS AND METHODS: 59 diabetic children (39 M; 29 F), age 1.2-11.5 years, and 67 controls (36 M; 31 F), age 1.2-11.7 years were included. Weight, height, body mass index (BMI), arm circumference, skin folds, fat mass and muscle areas were evaluated and transformed into standard deviation scores (SDS). RESULTS: Among the diabetic children the mean height SDS was -0.13 (± 0.97) while in the control group it was 0.28 (± 0.86) (p= 0.013). The difference between the first and the current height SDS showed that the height SDS decreased significantly (p< 0.001) and multiple regression analysis indicated correlation with the duration of the disease. The mean arm fat SDS also revealed difference (p< 0.001). The means for weight, BMI, addition of 3 skinfolds and muscle mass did not demonstrate difference between the groups. CONCLUSIONS: The diabetic children showed reduction of height SDS during the period studied and they were significantly shorter than the controls, even though their statures were within the population standards. The arm fat area also showed to be increased in relation with the controls.

A importância dos controles domiciliares na redução de internações em portadores de diabetes mellitus do tipo 1

Several therapeutic strategies have been used to improve control of patients with type 1 diabetes mellitus 1 (DM1), most of them based on capillary glycemia determinations. Considering the difficulty to have frequent capillary blood letting due to stress and the high cost of reagent strips for home glycemia determinations, we have often used glycosuria as a parameter of glycemia. In 1990 a group was established in our service to treat DM1 patients. Since 1992 all patients have been asked for home monitoring glycemia and glycosuria/ ketonuria. Free reagent strips were given to destitute patients. The aim of this work was to evaluate the benefits of home monitoring. We have correlated the outpatient number (P); the number of hospital admittances (I); the number of blood (S) and urine (U) reagent strips granted yearly; and the ratio for hospital admittances/followed up patients (I/P). We observed that, besides the increase in the number of patients in regular attendance, there was a decrease of 6 to 8-fold in hospital admittances compared to the same parameters obtained during 1989. These results are accompanied by an increase on the number of reagent strips distributed. An inverse correlation (r= -0.83; p< 0.05) between the number of urinary reagent strips distributed and the percentage of hospital admittances was found. Our results indicate that despite the low importance the literature gives to the urine test it can be considered as an important tool for controlling DM1 pediatric patients.

Crescimento e composição corporal de uma coorte de crianças e adolescentes com diabetes tipo 1

OBJECTIVE: To evaluate the growth and body composition of children and adolescents with type 1 diabetes mellitus (T1DM). SUBJECTS AND METHODS: A cohort of 44 patients with T1DM were followed up for approximately four years and compared with a control group. Weight, height, body mass index (BMI), body fat percentage (BF%), fat mass index, waist circumference (WC) and waist-height ratio were determined. RESULTS: In females, in the first evaluation, BF% was lower in patients than in controls, while in the second evaluation, mean WC was higher in patients than in controls. In males, height of the patients was lower in the first evaluation, while body mass index (BMI) was higher in the second one. We did not find any differences among the changes in height, weight and BMI z-scores and BF% or in the distribution of those z-scores between the two evaluations, in both groups. Multiple regression analysis found differences in BMI and waist-height ratio in both sexes and also in WC in females. CONCLUSION: The patients had adequate growth but showed discrepancy in their body composition during the study.

Phenotype of regulatory T cells in human type 1 diabetes at diagnosis and partial remission phase

Background Human type 1A diabetes (T1AD) has a broad spectrum of clinical presentations, which may be associated with the severity of autoimmune response and consequently, different levels of pancreatic beta cells destruction. The T1AD presents a partial remission phase. The remission phase is classically a short period in childhood-onset diabetes, but longer periods may occur especially in young.