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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/19397

Title: Hemostatic & Fibrinolytic Profile in Type 2 Diabetes Mellitus: Effect on the Incidence & Severity of Diabetic Complications
Authors: Al Ayoubi, Samha Mohamed Zohair
Al Daghri, Dr. Nasser
Keywords: Hemostatic
Type 2 Diabetes
Severity of Diabetic Complications
Issue Date: 17-Jan-2010
Abstract: Diabetes mellitus can perturb normal hemostatic functions which include platelets, coagulation/anticoagulation and fibrinolytic functions through a variety of mechanisms, including disrupting the normal function of vascular endothelial cells and coagulation factors. Since the hemostatic and fibrinolytic processes are highly intricate, disruption at any stage can be profoundly deleterious to proper functioning. The aim of the present work was to conduct a pilot study on adult Saudi diabetics which assesses the hemostatic and fibrinolytic status. These statuses might be considered risk factors affecting the occurrence of vascular complications among these subjects. Three groups of subjects were recruited to the study: the control group (group 1, n = 23 subjects: 11 male and 12 female), the diabetics group (group 2, n=114 subjects: 64 male and 50 female). Group 2 was further subdivided into diabetics without complications (group 2-A, n = 60 patients: 28 male and 32 female) and diabetics with complications (group 2-B, n = 54: 36 male and 18 female). Biochemical measurements (fasting plasma glucose, fasting insulin, glycated hemoglobin, lipid profile, liver function tests and renal function tests); complete blood count; coagulation parameters (ADP-induced platelet aggregation, flow cytometric analysis of the platelet basal activation state, prothrombin time (PT), activated partial thromboplastin time (APTT), and tissue factor-pathway inhibitor both total and free); and fibrinolytic parameters (plasma levels of plasminogen activator inhibitor-1; PAI-1) were assessed in the studied subjects. Microsoft Excel and SPSS software were used to statistically analyze the obtained results. The results of the present study indicate that in type 2 diabetic Saudi patients, some of the components of the hemostatic and fibrinolytic systems are altered. Platelets circulate in higher number in diabetics vs. the healthy control. Platelet count decreased in the complicated diabetics vs. the uncomplicated patients. Moreover, platelets from diabetics show hypo-responsiveness to ADP that is not affected by the presence or absence of diabetic complications. Intriguingly, the platelets of diabetics circulate in a hyperactive state as demonstrated by forming platelet monocyte aggregates. Moreover, diabetic patients demonstrate a shorter PT as compared to control subjects. This indicates a hypercoagulable state that specifically affects the extrinsic coagulation pathway. This procoagulable state, in addition to the impaired fibrinolysis as manifested by elevated PAI-1, signals a hazardous situation that represents a risk factor capable of precipitating thrombovascular complications in uncontrolled diabetic patients at any point. The present study also demonstrates that the circulating levels of PAI-1 are elevated in the diabetic group as compared to the control healthy group. Circulating levels of PAI-1 in the diabetic group correlate significantly with obesity measures. This finding might be related to the common pathophysiologic mechanisms of obesity and diabetes; where both are known to have a strong association with a subclinical chronic inflammation. In Conclusion, the metabolic changes in diabetes with imbalance of platelet activity, haemostasis and fibrinolysis, favor an altered thrombotic milieu. Results of the current study demonstrate disturbed balance between these components of the hemostatic system. Noticeably, both hypercoagulability state and bleeding tendency were observed. This might play a role in precipitating a particular diabetic complication versus another. Specifically, these systemic changes may result in an increased thrombosis-driven atherosclerotic process, in part explaining the increased incidence of cardiovascular complications found in patients with type 2 diabetes. Indeed, more research is needed to elucidate these mechanistic bases of various diabetic complications and possibly target them with tailored therapeutic measures.
URI: http://hdl.handle.net/123456789/19397
Appears in Collections:College of Science

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