Extended family history of diabetes and autoimmune diseases in children with and without type 1 diabetes.

Objective: To determine the extended family history of diabetes or autoimmune diseases in families with and without children having type 1 diabetes.

Research Design And Methods: Three hundred case families and 381 control families were interviewed using structured questionnaires.

Results: The proportion of case children having at least one relative with type 1 diabetes outside the nuclear family was higher than that of control children (50.

Prediction of type 1 diabetes in the general population.

Objective: To evaluate the utility of GAD antibodies (GADAs) and islet antigen-2 antibodies (IA-2As) in prediction of type 1 diabetes over 27 years in the general population and to assess the 6-year rates of seroconversion.

Research Design And Methods: A total of 3,475 nondiabetic subjects aged 3-18 years were sampled in 1980, and 2,375 subjects (68.3%) were resampled in 1986.

Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial.

Background: In mouse models of diabetes, prophylactic administration of insulin reduced incidence of the disease. We investigated whether administration of nasal insulin decreased the incidence of type 1 diabetes, in children with HLA genotypes and autoantibodies increasing the risk of the disease.

Methods: At three university hospitals in Turku, Oulu, and Tampere (Finland), we analysed cord blood samples of 116 720 consecutively born infants, and 3430 of their siblings, for the HLA-DQB1 susceptibility alleles for type 1 diabetes.

Early epitope- and isotype-specific humoral immune responses to GAD65 in young children with genetic susceptibility to type 1 diabetes.

Objective: The pattern of the humoral immunity to disease-associated autoantigens may reflect the severity of the autoimmune disease process. The purpose of this study was to delineate the maturation of the humoral immunity to one of the main autoantigens in type 1 diabetes (T1D), glutamic acid decarboxylase (GAD65).

Design And Methods: Serum samples were obtained for the detection of epitope- and isotype-specific antibodies sequentially with short intervals from 36 young children with HLA-conferred genetic susceptibility to T1D starting from the first appearance of GAD65Ab.

Soluble adhesion molecules in young children with signs of beta-cell autoimmunity--prospective follow-up from birth.

Background: This study aimed at evaluating the relationship between the circulating concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and sL-selectin and the appearance of beta-cell autoimmunity, and at assessing whether these molecules could assist in the identification of environmental factors implicated in the immune process damaging the pancreatic beta-cells.

Methods: Serum levels of soluble adhesion molecules were measured with enzyme-linked immunosorbent assays over the first 2 years of life in 65 children seroconverting to positivity for autoantibodies and 65 control children, all with HLA-conferred susceptibility to type 1 diabetes (T1D).

Results: The total integrated concentrations of soluble adhesion molecules were comparable between the two groups.

Familial clustering of beta-cell autoimmunity in initially non-diabetic children.

Background: Type 1 diabetes is characterised by familial aggregation. We set out to explore whether beta-cell autoimmunity, which is considered to precede clinical disease, also shows familial clustering.

Methods: Tests for HLA DQB1 alleles (*02, *0301, *0302, *0602) and islet cell autoantibodies (ICA) were performed on 5836 children from 2283 families.

Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of beta-cell autoimmunity in a high-incidence country.

Objective: To assess possible differences in the frequency of HLA-DQB1 risk genotypes and the emergence of signs of beta-cell autoimmunity among three geographical regions in Finland.

Research Design And Methods: The series comprised 4,642 children with increased HLA-DQB1-defined genetic risk of type 1 diabetes from the Diabetes Prediction and Prevention (DIPP) study: 1,793 (38.6%) born in Turku, 1,646 (35.

Insulin autoantibody isotypes during the prediabetic process in young children with increased genetic risk of type 1 diabetes.

This work aimed to assess the maturation of the humoral immune response to insulin in preclinical type 1 diabetes by observing the emergence of various isotypes of insulin autoantibodies (IAA) in children with HLA-DQB1-conferred disease susceptibility. The series was derived from the Finnish Type 1 Diabetes Prediction and Prevention Study and comprised 15 IAA-positive children who presented with type 1 diabetes during prospective observation (progressors) and 30 children who remained nondiabetic (nonprogressors). An isotype-specific radiobinding assay was used to determine isotype-specific IAA (IgG1-4 and IgA) from samples obtained with an interval of 3-12 mo.

Enterovirus infections are associated with the induction of beta-cell autoimmunity in a prospective birth cohort study.

Enterovirus infections have been associated with the manifestation of clinical type 1 diabetes in a number of reports, and recent prospective studies have suggested that enterovirus infections may initiate the autoimmune process, leading to the disease. In the present study, we analyzed the role of enterovirus infections in a Finnish birth cohort study, Diabetes Prediction and Prevention (DIPP), in which all newborn infants are screened for diabetes-associated HLA-DQB1 alleles, and those with an increased genetic risk are invited for prospective follow-up. Enterovirus infections were diagnosed by serology and reverse transcriptase-polymerase chain reaction (RT-PCR) from serum samples taken from birth every 3-6 months.

Autoantibodies to GAD, IA-2 and insulin in ICA-positive first-degree relatives of children with type 1 diabetes: a comparison between parents and siblings.

Background: Islet cell antibodies (ICA) represent a heterogenous group of autoantibodies to diabetes-associated antigens, including glutamic acid decarboxylase (GAD) and the IA-2 protein. The objectives of the present study were to compare the prevalence of autoantibodies to known biochemically characterized autoantigens between ICA-positive non-diabetic parents and siblings of children with type 1 diabetes and to evaluate how such antibodies explain ICA reactivity.

Methods: The presence and levels of GAD antibodies (GADA), IA-2 antibodies (IA-2A) and insulin autoantibodies (IAA) were analyzed in the sera of 184 ICA-positive first-degree relatives (79 parents and 105 siblings).

Genetic risk determines the emergence of diabetes-associated autoantibodies in young children.

Timing of onset of autoimmunity is a prerequisite for unmasking triggers and pathogenesis of type 1 diabetes. We followed 4,590 consecutive newborns with 8 or 3% HLA-DQB1 conferred risk for type 1 diabetes at 3-, 6-, or 12-month intervals up to 5.5 years of age.