Antibodies to GAD65 epitopes at diagnosis and over the first 10 years of clinical type 1 diabetes mellitus.

Antibodies to glutamate decarboxylase (GAD65Ab) may persist, and their titres even increase after the clinical onset of type 1 diabetes. To characterize this phenomenon in detail, we analysed sequentially antibodies to GAD65 epitope clusters in a radio-binding assay in patients with type 1 diabetes. Serum samples were taken at diagnosis and 2, 5 and 10 years later from 50 young patients who had tested positive for GAD65Ab at least once during observation.

Natural course of preclinical type 1 diabetes in siblings of affected children.

Aim: To define the dynamics of preclinical type 1 diabetes in siblings of affected children and to characterize the siblings experiencing a progressive process.

Methods: From 801 families taking part in the "Childhood Diabetes in Finland" (DiMe) Study, 715 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the initial number of disease-associated autoantibodies detectable close to the time of diagnosis of the index case, while another classification system covering 641 of the siblings was based on a combination of the initial number of antibodies and the first-phase insulin response (FPIR) to intravenous glucose.

Results: Based on the first classification, there was a total of 95 siblings with initial signs of prediabetes, out of whom 34 (36%) progressed, 26 (27%) remained stable and 35 (37%) regressed during prospective observation for a median of 3.

Genetic modification of risk assessment based on staging of preclinical type 1 diabetes in siblings of affected children.

We set out to study the association between human leukocyte antigen-defined genetic disease susceptibility and the stage of preclinical type 1 diabetes and whether genetic predisposition affects the natural course of preclinical diabetes in initially nondiabetic siblings of affected children. A total of 701 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the initial number of disease-associated autoantibodies detectable close to the time of diagnosis of the index case: no prediabetes (no antibodies), early (one antibody specificity), advanced (two antibodies), and late prediabetes (three or more antibodies). Another classification system covering 659 siblings was based on a combination of the initial number of antibodies and the first-phase insulin response (FPIR) to iv glucose: no prediabetes (no antibodies), early (one antibody specificity, normal FPIR), advanced (two or more antibodies, normal FPIR), and late prediabetes (at least one antibody, reduced FPIR).

Time-resolved fluorometric assay for detection of autoantibodies to glutamic acid decarboxylase (GAD65).

Background: Type 1 diabetes mellitus results from destruction of the pancreatic insulin-producing beta cells by a chronic autoimmune process. Methods are needed for the detection of circulating autoantibodies to glutamic acid decarboxylase (GAD65), a major marker of this process.

Methods: Streptavidin-coated microtiter plates were incubated with biotinylated GAD65, and after incubation with serum samples from patients with type 1 diabetes mellitus and control individuals, europium-labeled GAD65 was added.

Soluble adhesion molecules in pre-clinical Type 1 diabetes: a prospective study.

Aims: This prospective case-control study aimed at evaluating the time course of serum concentrations of soluble adhesion molecules; intercellular adhesion molecule-1 and L-selectin in siblings with signs of pre-clinical Type 1 diabetes in order to relate these concentrations to autoantibody status and to assess whether these markers could discriminate between those siblings who progressed to clinical diabetes and those who remained non-diabetic.

Methods: Serum levels of soluble adhesion molecules were measured with enzyme-linked immunosorbent assays in autoantibody-positive initially healthy siblings of diabetic children who progressed to clinical disease during the observation period of 10 years and in sex- and age-matched autoantibody-positive siblings who have remained unaffected.

Results: The intraindividual and interindividual variability in the concentrations of soluble adhesion molecules was conspicuous both among the progressors and non-progressors.