Soluble adhesion molecules in preclinical type 1 diabetes

We measured the concentrations of the soluble forms of the intercellular ad hesion molecule-1 (sICAM-1) and L-selectin in 95 autoantibody-positive sibl ings of children with type 1 diabetes and 95 sex- and age-matched siblings testing negative for diabetes-associated autoantibodies to assess the possi ble role of soluble adhesion molecules as markers of progressive beta -cell destruction in preclinical diabetes and their ability to discriminate betw een those siblings who progress to clinical disease and those who remain no ndiabetic. We observed an inverse correlation between age and the levels of both sICAM-1 (r = -0.31, p ( 0.001) and SL-selectin (r = -0.27, p < 0.001) in the control siblings but no association with HLA-DR phenotypes. There w as no difference in the circulating levels of soluble adhesion molecules be tween the antibody-positive and negative siblings. Among the antibody-posit ive siblings, those with at least three autoantibodies had higher sICAM-1 l evels (p < 0.01) than those testing positive for only one, and siblings wit h three autoantibodies or more had higher concentrations of SL-selectin (p < 0.01) than those with two autoantibodies. Siblings with an islet cell ant ibody level of 20 Juvenile Diabetes Foundation units or more had higher sIC AM-1 concentrations than those with a level below 20 (p < 0.001), and those testing positive for antibodies to the protein tyrosine phosphatase-relate d IA-2 antigen had increased levels of both sICAM-1 (p = 0.03) and SL-selec tin (p = 0.02) compared with siblings who tested negative. The antibody-pos itive siblings who progressed to clinical type 1 diabetes were significantl y younger than the nonprogressors (p ( 0.001) and had higher levels of sICA M-1 initially (p < 0.001). The difference in sICAM-1 concentrations remaine d significant (p = 0.03) after age adjustment. Our results indicate that co ncentrations of soluble adhesion molecules are increased in the autoantibod y-positive siblings who have the highest risk of developing clinical diabet es, suggesting that <beta>-cell destruction is reflected in increased circu lating levels of these molecules. This is supported by the observation of e levated sICAM-1 concentrations in the 29 siblings who actually progressed t o clinical type 1 diabetes. Peripheral levels of soluble adhesion molecules are not able to discriminate between progressors and nonprogressors, howev er, due to substantial overlapping between these two groups.