Use of an islet cell antibody assay to identify type 1 diabetic patients with rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes Registry.

Abstract

OBJECTIVE -To investigate whether the presence of antibody markers at diagnosis could help predict the rapid decrease in residual ␤-cell function noted in some, but not all, patients with recent-onset type 1 diabetes.RESEARCH DESIGN AND METHODS -We measured random C-peptide levels (radioimmunoassay); islet cell cytoplasmic antibodies (ICA) (indirect immunofluorescence); and antibodies against IA-2 protein, 65-kDa glutamate decarboxylase, and insulin (liquid-phase radiobinding assays) in 172 patients Ͻ40 years of age with type 1 diabetes. The patients had been consecutively recruited at diagnosis by the Belgian Diabetes Registry and were followed for 2 years.RESULTS -Two years after diagnosis, random C-peptide levels had decreased significantly (P Ͻ 0.001) in ICA ϩ patients but not in ICA Ϫ patients. C-peptide values Ͻ50 pmol/l were noted in 88% of patients diagnosed before 7 years of age, in 45% of patients diagnosed between ages 7 and 15 years, and in 29% of patients diagnosed after 15 years of age (P Ͻ 0.001). In cases of clinical onset before age 15 years, a rapid decline in random C-peptide values was observed almost exclusively in patients with high-titer ICA (Ն50 Juvenile Diabetes Foundation [JDF] units) at diagnosis (69 vs. 17% in patients with lower ICA titers, P Ͻ 0.001). In patients diagnosed after 15 years of age, 36% of patients with ICA titers Ն12 JDF units developed low C-peptide levels compared with 14% of patients with ICA titers Ͻ12 JDF units (P Ͻ 0.03). Multivariate analysis confirmed that C-peptide levels after 2 years were inversely correlated with ICA levels (P Ͻ 0.001) and to a lesser degree positively correlated with age at diagnosis (P Ͻ 0.02), regardless of the levels or number of molecular autoantibodies.CONCLUSIONS -Young age at diagnosis and high-titer ICA identify a group of type 1 diabetic patients at high risk of rapidly losing residual ␤-cell function. Using these selection criteria, it is possible to better target ␤-cell-preserving interventions to patients with or without such rapid progression, depending on the nature of the tested substance. The

Time dynamics of autoantibodies are coupled to phenotypes and add to the heterogeneity of autoimmune diabetes in adults: the HUNT study, Norway

“…Fluctuations in antibody levels such as GADA are common in type 1 diabetes in childhood and adolescence and their disappearance is not closely linked to progression or lack of progression to beta cell failure [14,15]. Such findings may contrast with the lesser degree of progression seen here in GADA losers vs persisters.…”

An Association of Autoantibody Status and Serum Cytokine Levels in Type 1 Diabetes

“…After clinical onset of the disease, different characteristics have been noted for patients who were either positive or negative for islet autoantibody (12)(13)(14)(15)(16)(17)(18)(19)(20). In addition, high and multiple islet autoantibody titers may be an early sign of a rapid disease progression in terms of loss of residual ␤-cell function during the first years of disease (21)(22)(23)(24)(25)(26). The latter association was not found in all studies (27,28).…”

“…In addition, multiple autoantibody positivity and titer seem relevant (21)(22)(23)(24)(25)(26). It therefore seems relevant that multiple islet autoantibody-positive patients can be clearly distinguished from autoantibody-negative patients on the basis of systemic cytokine/chemokine concentrations.…”

Autoimmune Diabetes Not Requiring Insulin at Diagnosis (Latent Autoimmune Diabetes of the Adult)

“…Islet ␤-cell function is often partially preserved at the onset of type 1 diabetes, particularly in the older-onset patients (48). There is evidence that residual ␤-cell function can be preserved.…”