Soluble adhesion molecules in Finnish schoolchildren with signs of preclinical type 1 diabetes

Abstract

Background: We measured the circulating concentrations of the soluble forms of intercellular adhesion molecule-1, ICAM-1 (sCD54) and L-selectin (sCD62L) in 104 non-diabetic Finnish schoolchildren testing positive for one or more diabetes-associated autoantibodies and in 104 autoantibody-negative children to elucidate the relationship between soluble adhesion molecules and humoral, genetic and metabolic markers of preclinical type 1 diabetes.

Methods: Specific enzyme-linked immunosorbent assays were used to analyse serum sICAM-1 and sL-selectin concentrations.

Results: The sICAM-1 and sL-selectin levels were comparable in the autoantibody-positive and control children, even when comparing children with multiple autoantibodies with those having one or no autoantibodies. The IA-2A titres in children testing positive for this autoantibody correlated with the sICAM-1 concentrations (rs=0.62, P=0.05), but otherwise no significant associations were seen between the autoantibody specificities and the concentrations of soluble adhesion molecules. Control children with HLA DQB1 genotypes conferring a low or decreased risk of type 1 diabetes had higher levels of sL-selectin than those with high or moderate risk genotypes (P=0.04). sL-selectin concentrations were significantly increased in the autoantibody-positive children with a first-phase insulin response (FPIR) below the 5th (n=11;P=0.026) or 10th percentiles (n=17;P=0.009) relative to the children with a normal FPIR. No associations were observed between sICAM-1 concentrations and DQB1 genotypes or FPIR.

Conclusions: The data indicate that there are a few conspicuous signs of endothelial/leukocyte activation reflected in increased circulating levels of soluble adhesion molecules in schoolchildren who are positive for markers of preclinical type 1 diabetes. The correlation between sICAM-1 concentrations and IA-2A levels in the IA-2A-positive children suggests that the former may increase in late preclinical type 1 diabetes, as IA-2A are the last autoantibodies to appear in the prediabetic process. Increased sL-selectin concentrations in subjects with impaired beta-cell function may reflect an active destructive insulitis process.