Impaired fibrinolysis and early atherosclerosis in impaired glucose tolerance and newly detected type 2 diabetes

Impaired fibrinolysis has been suggested to contribute to excessive atheros clerosis in diabetes. However, the role of defective fibrinolysis in the ea rly stages of atherosclerosis in the prediabetic phase remains unclear. Sin ce the intima-media thickness (IMT) of the common carotid artery is a good indicator of early atherosclerosis, we examined the relationship of fibrino lytic parameters - plasminogen activator inhibitor-1 (PAI-1) antigen (activ e and total) and tissue-type plasminogen activator (tPA) antigen with ather osclerosis risk factors and carotid IMT in various degrees of glucose intol erance. 424 middle-aged subjects were examined - 249 with normal glucose to lerance (NGT), 107 with impaired glucose tolerance (IGT) and 68 with newly diagnosed diabetes mellitus (NDM). IMT of the common carotid artery was exa mined by B-mode of ultrasound. Fibrinolytic parameters (PAI-1 antigen and t PA antigen) and plasma lipoproteins - triglycerides, total and HDL choleste rol were measured by conventional methods; real insulin and proinsulin by h ighly specific enzyme immunoassays. The diabetic individuals showed significantly higher PAI-1 antigen in compa rison to the NGT and IGT group. TPA antigen was significantly higher in the NDM group, however, this difference disappeared after age and sex adjustme nt. PAI-1 (total and active) and tPA antigen raised in quintiles for fastin g plasma glucose below the cut-off limits for diabetes. IMT increased in qu intiles for PAI-1 active antigen with a significant difference between the Ist and the 5th quintiles, However, this difference was no longer statisica lly significant after adjustment for age and sex. PAl-1 and tPA antigen wer e significantly positively correlated with atherosclerosis risk factors: bo dy mass index, waist to hip ratio, fasting and postprandial plasma glucose, HbA1c, real insulin, proinsulin, triglycerides, total cholesterol and inve rsely to HDL cholesterol. In addition PAI-1 and tPA antigen correlated sign ificantly to carotid IMT. In conclusion: we observed impaired fibrinolysis already in prediabetic subjects. PAl-1 and tPA antigen correlate to the est ablished components of the metabolic syndrome and to carotid IMT.