Hrombin Activatable Fibrinolysis Inhibitor (TAFI) Relationship with Insulin Resistance and Other Risk Factors of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus (DM)

4 Abstract: Type 2 Diabetes Mellitus (DM), is a global public health crisis that threatens the economies of all nations, particularly developing countries. Diabetes affects at least 285 million people worldwide and the number is expected to reach 438 million by the year 2030. Egypt is an African country with a population (82 million). By the 2025, Egypt is expected to be among the top ten countries that have the highest prevalence rates of diabetes in the world, notably type 2 DM. Cardiovascular complications are the main cause of mortality in patients with diabetes. Premature atherosclerosis, increased platelet reactivity and activation of coagulation factors with associated hypo fibrinolysis all contribute to increased cardiovascular risk in this population. In fact, type 2 DM is considered the most frequent acquired thrombophilic state. Under physiological conditions, fibrinolytic system is responsible for the lysis of fibrin clot, thus maintaining the blood fluidity. Recently, a new potent inhibitor of fibrinolysis, TAFI was isolated from human plasma. To determine plasma concentrations of TAFI in patients with type 2 DM and its relation to insulin resistance and other risk factors for cardiovascular disease like duration of type 2 DM and serum cholesterol (chol.), triglyceride (TG), uric acid and body mass index (BMI). Eighty individuals were included in the study, classified into three groups Group1: 30 patients with type 2 DM with duration of disease less than one year. Group2: 30 patients with type 2 DM with duration of disease more than ten years. DM was diagnosed according to the criteria of the American Diabetes Association (ADA), 2009. Group3: control group, consists of 20 healthy volunteers who are age and sex matched to the patients. All groups were subjected to the following: (1) Full medical history (2) Full clinical examination. (3) Laboratory investigations: Serum fasting and postprandial blood glucose, urea, creatinine, uric acid, sodium, potassium, calcium, phosphorous, bilirubin, ALT, AST, albumin, triglyceride, total cholesterol, TAFI and insulin were done. Also, urine analysis, ECG, fundus examinations were done. In each subject, the degree of insulin resistance was estimated by Homeostasis Model Assessment Insulin Resistance (HOMA- IR). Low HOMA-IR values indicate high insulin sensitivity, whereas high HOMA-IR values indicate insulin resistance. There were highly statistical significant increases in TAFI, fasting and postprandial blood glucose, serum cholesterol, triglyceride, uric acid, insulin and HOMA-IR value for groups 1, 2 compared with group 3. In both groups 1 and 2, TAFI showed a significant positive correlation with FBG and HOMA-IR but it showed non-significant correlation with the postprandial blood glucose, cholesterol, triglyceride, BMI and uric acid. On the other hand, there was highly statistical significant increase in TAFI, insulin, serum cholesterol but non statistical significant increase in HOMA-IR value for group 2 compared with group1. In this study, we found increased level of TAFI in type 2 D.M patients in both groups compared to healthy subjects. The increased TAFI level in type 2 D.M. was more in group 2 than group 1. The increased level of TAFI was correlated positively with FBG and HOMA-IR value. Coexistence of the high fasting blood glucose, increased HOMA-IR value and duration of disease synergistically accelerates impairment of fibrinolysis via elevated concentrations of TAFI which is a risk factor for the occurrence of cardiovascular complication in patients with type 2 DM.