Atherogenesis in IDDM: a family study of contributing factors

摘要

Parameters of significance in atherogenesis were investigated in IDDM children (n=45), their parents (n=65) and siblings (n=17) as well as in unrelated healthy controls (n=51), their HLA DQ status, and the relationship between groups on the basis of discriminant analysis was established. Level of plasma lipids (total, HDL, LDL cholesterol, triglycerides and Lp (a) lipoprotein, markers of platelet activation (GMP-140, GPIIb/IIIa, microparticles, platelet aggregates) and fibrinolysis (tissue type plasminogen activator - t - PA and inhibitor - PAI-1 as well as its active form) were measured. Slight elevation of plasma lipids in IDDM patients in comparison to controls and siblings was not significant. The group of parents was characterized by the highest level of lipids, especially compared to controls (LDL p=0.03 and total cholesterol p=0.004). A tendency to a decrease of both plasminogen inhibitors (PAI-1 and its active form), as well as its activator (t-PA) concentration in the IDDM group was observed. However, the fraction of activated platelets in IDDM was dramatically enhanced (7.5±2.3% of cell population) in contrast to parents - 1.5±0.2% (p=0.002), siblings - 1.3±0.2% (NS), and controls - 1.4±0.2% (p=0.003). Similarly an elevation of platelet microparticles formation in the IDDM group, both before and after activation with thrombin, was observed. Stepwise discriminant analysis of the platelet parameter values revealed the highest discrepancy between the IDDM patients and controls (p=0.000001). Differences between IDDM children and their siblings (p=0.001) as well as parents (p=0.008) were less significant involvement of genetic factors affecting platelet response is suggested since the control group, represented by unrelated subjects, is particularly well separated from others more closely related. Analysis of the presence of HLA DQA152 and HLA DQB157 codons excludes their involvement in this altered platelet response. Data suggest that long lasting hyperglycemia in IDDM children is the most effective factor in atherogenic alterations, whereas in parents age-dependent factors are involved in the same type of changes.