Insulin, endothelin-1, homocysteine, plasminogen activator inhibitor-1 and C-reactive protein as novel brisk factors for systemic atherosclerosis in diabetic patients

ABSTRACT

Aim: The aim of the present study was to find out the contributing role of ET-1, PAI-1, homocysteine, and CRP [C- reactive protein] with regard to the increasing risk for the development of atherosclerosis in diabetic patients. The study included 30 metabolically-controlled diabetics, 15 of them belonged to type 1, and 15 type 2 diabetics. Blood glucose levels, HbAIc, lipid profile, plasma C- peptide, homocysteine, CRP, and fibrinogen were assayed basally, whereas ET-1 and PAI-1 levels were assayed both basally and at 120 and 180 minutes during the euglycemic hyperinsulinemic clamp technique. Basal levels of homocysteine, C- reactive protein and fibrinogen were within normal range in both types of diabetes. There was a significant increase in the mean basal levels of ET-1 and PAI-1 in type 2 diabetics when compared to their mean basal levels in type 1 diabetes. Moreover, ET-1 and PAI-1 levels were significantly higher at 120 and 180 minutes when compared to their basal levels. Also, ET-1 and PAI-1 levels at 120 and 180 minutes were significantly higher in type 2 diabetics when compared to their levels in type 1 diabetics. There was a significant positive correlation between the daily dose of exogenous insulin and basal levels of ET-1 and PAI-1 in type 1 diabetes, and between the mean basal C- peptide level and the mean basal ET-1 and PAI-1 levels in type 2 diabetics. Conclusions: Insulin stimulates ET-1 expression in patients with diabetes. The plasma ET-1 concentration is related to endogenous insulin secretion and therefore to insulin resistance. As a consequence of higher endogenous insulin secretion, patients with type 2 diabetes have higher levels of plasma ET-1 than patients with type 1 diabetes. This level was maintained significantly higher at 120 and 180 minutes in type 2 diabetics when compared to its level in type 1 diabetes. Moreover, patients with type 2 diabetes have significantly higher levels of PAI-1 than patients with type 1 diabetes. Therefore, in diabetics, the impairment of fibrinolytic system may affect the development and progression of atherosclerosis