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

Abstract

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. Integrated concentrations (area-under-the curve) of intercellular adhesion molecule-1 over a period of 6 to 48 months before the diagnosis was higher in the progressors ( p=0.035), the difference being most evident 18 to 24 months before diagnosis ( p=0.015). The integrated concentrations of soluble L-selectin were similar in progressors and non-progressors over the total pre-clinical period. There were no differences in the integrated concentrations of soluble adhesion molecules in relation to the initial or maximal number of autoantibodies detected during the follow-up.

Conclusion/interpretation: These observations suggest that the process of destructive insulitis could be initiated approximately 4 years before the manifestation of clinical diabetes, being most active about 1.5 years before diagnosis. Peripheral concentrations of soluble intercellular adhesion molecule-1 or L-selectin are not helpful in the identification of those prediabetic subjects who will progress to clinical disease over the next 10 years, since there is substantial overlapping in these concentrations between progressors and non-progressors.