Interleukin 18 and sICAM-1 serum levels in families with type 1 diabetes mellitus

It is well known that subjects with type 1 diabetes are at an increased risk of death from coronary heart disease in comparison to non-diabetic age-matched individuals because hyperglycaemia is believed to be a key risk factor for the development of micro- and macrovascular complications. On the other hand there is increasing evidence about the role of inflammatory mediators in the pathogenesis of atherosclerosis and the development of acute coronary syndromes. It has been recently suggested that IL-18 and sICAM-1 have a strong predictive value for cardiovascular diseases and deaths in patients with coronary artery disease and/or in apparently healthy men. The aim of our study was to estimate the serum levels of IL-18 and sICAM-1 in subjects with type 1 diabetes and their relatives, who share HLA diabetic susceptibility genes (with or without pancreatic autoantibodies), but still without glucose level disturbances, as an evaluation of the possible role of genetic predisposition to the presence of IL-18 in diabetic families. The study was carried out in 35 type 1 diabetic subjects, their 101 healthy first-degree relatives: 36 siblings and 65 parents and the control group consisted of 31 healthy volunteers. We have found increased IL-18 and sICAM-1 levels in subjects with type 1 diabetes and their first degree relatives, who share diabetic HLA haplotypes: DRB1*03/DRB1*04 or DRB1*03/*04/DQB1*02 independently of their autoimmune status. There was a strong positive correlation between IL-18 and sICAM-1 levels in diabetic subjects and their first degree relatives without glucose level disturbances. To our knowledge this is the first study, which suggests that sICAM-1 elevations could be a result of IL-18 overproduction in type 1 diabetic subjects and their first degree relatives. Since in previous studies IL-18 and sICAM-1 were found to be predictors of death in subjects with CHD, one could speculate that high levels of IL-18 observed in subjects with genetic predisposition, but still with normal glucose levels, are an in addition to hyperglycaemia, pathogenic factors responsible for a higher risk of acute coronary events in subjects with diabetes type 1.