الفهرس 
Diabetes mellitusOnly 14 pages are availabe for public view
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Abstract
Diabetes is a chronic disease becoming one of the world’s biggest health problems owing to the projected increase in new cases, Diabetes is associated with an increased risk of peripheral vascular disease (PVD). The abnormal metabolic state in diabetes affects both structure and function of the vessels, resulting in accelerated atherogenesis and poor outcomes. Endothelial dysfunction, vascular smooth muscle cell dysfunction, inflammation and hypercoagubility are the key factors in diabetic arteriopathy.
Type 2 is the most common form of diabetes, Type 2 diabetic patients are at high risk of cardio-vascular complication, Individuals with type2 diabetes have a 2- to 4-fold increased risk of developing atherosclerotic vascular disease. The primary cause of mortality in the majority of patients with diabetes is often presenting as acute coronary synd-romes. Acute coronary syndromes are precipitated by the ischaemic effect of an occlusive intracoronary thrombus which develops over a ruptured theromatous plaque .
Type 2 diabetes may be responsible for Endothelial dysfunction, vascular smooth muscle cell dysfunction, hyper-coagubility, decrease in fibrinolysis ,Impaired platelet function, Coagulation abnormality , Inflammation and Elevated CRP concentrations,reduction of the anti-coagulant property of vascular endothelium, all this factors have been implicated in diabetic microvascular and macrovascular complications .
Platelet hyperactivity (in combination with abnormalities in coagulation and fibrinolysis), which is characteristic in diabetes, undoubtedly, contributes to this as platelets play a pivotal role ininitiating and sustaining thrombi within vessels.
It has been found that increased coagulation activation is a critical factor in macrovascular thrombus formation in type 2 diabetic patients .
Increased intima-medial thickness IMT is a risk factor for coronary heart disease and reflects systemic athero-sclerosis in diabetic patients .
Accelerated atherosclerosis secondary to endothelial dysfunction, inflammation, thrombosis, oxidative stress, dyslipidaemia and hemodynamic shear stress plays an important facilitative role in the longterm development of vascular disease in patients with type 2 diabetes ,In atherosclerotic disease , Endothelial thrombomodulin has been shown to be down regulated , which may further adversely affect the function of protein C ( PC ) system . Atherosclerosis may induce resistance to activated protein C by other mechanism partly depen-dant on increase in factor VIII levels (released from endothelial cells) .
TM on vascular endothelial cells is an important molecule in human natural anticoagulation system Thrombin- Thrombomodulin complex becomes an activator of protein C which inactivates factors Va and VIIIa and thereby inhibits the blood coagulation cascade Thrombomodulin is not only found bound to endothelial cells, soluble forms of thrombomodulin (sTM) are also present in the circulation.
Up to seven molecular subspecies of sTM have been reported soluble TM fragments circulate in the plasma and are found at increased levels in various diseases such as cardiovascular disease and diabetes a prothrombotic state and endothelial dysfunction could enhance the risk of ischemic manifestations of type 2 diabetes , Thus, as a vasoprotective molecule, thrombomodulin is involved in the pathophysiology of type 2 diabetes and diabetic vascular disease .
There was significant increase in soluble thrombomodulin in Type 2 diabetic patients especially with peripheral ischemia compared to control group ,renal impairment was significantly higher in Type 2 diabetic patients especially with peripheral ischemia compared to diabetic ones . There was significant positive correlation between plasma soluble thrombomodulin and 2HPP, microalbuminuria .
Three groups of individuals were included in the study; group I, including 20 patients with type 2 diabetes mellitus with ischemia, group II, including 20 type 2 diabetes mellitus , and group III which included 20 apparently healthy individuals (control). Quantitative assays of serum Thrombomodulin , using commercially supplied ELISA were performed for all individuals.
Statistically high significant differences as regards serum levels of Thrombomodulin were found between the 3 studied groups with group I having the highest levels. Furthermore, microalbuminuria statistically significant higher levels in group I when compared to group II. Additionally, correlation studies have revealed significant positive correlations between serum levels of Thrombomodulin and 2HPP, microalbuminuria among diabetic individuals.
According to the results of the present study; it was concluded that high serum levels of Thrombomodulin are associated with diabetes and Additionally, the correlation between serum levels of Thrombomodulin and 2HPP, microalbuminuria suggests that the dysregulated Thrombomodulin secretion might contribute to diabetic vascular disease.
the present study demonstrates significantly elevated levels of serum Thrombomodulin in type 2 diabetic patients and that their is higher increase in serum Thrombomodulin level especially in peripheral ischemic type 2 diabetic patients especially. Furthermore, significant positive correlations between elevated levels of serum Thrombomodulin and 2HPP, microalbuminuria .have been obtained. This suggest that the dysregulated thrombomodulin secretion and elevated levels of serum Thrombomodulin encountered in type 2 diabetes with peripheral ischemia.