الفهرس 
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Abstract
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels.
Low grade inflammation and activation of theimmune system play a role in the common pathogenesis of both insulin resistance and endothelial dysfunction and subsequently the development of type 2 diabetesand atherosclerosis.
Dysfunction of the vascular endothelium is considered an important factor in the pathogenesis of diabetic micro- and macroangiopathy. It precedes by decades morphological atherosclerosis and cardiovascular complications.
AIF-1, is a 17 kDa conserved structural cytoplasmic, calcium-binding, inflammation-responsive scaffold protein.It is also known as ionized calcium-binding adaptor molecule - 1 (Iba1).It is one of the EF hand proteins’ family.
AIF-1 was originally identified in rat cardiac allografts with chronic rejection. In humans,AIF-1 is involved in many pathological processes but is expressed primarily in dendritic cells and macrophages. also, it has been found in many other types of cells including activated T cells, vascular endothelial cells and blood vessel smooth muscle cells after a balloon injury,. thus AIF1 represents a cytokine-inducible, tissue-specific, and highly conserved transcript transiently expressed in response to vascular trauma. A substantial body of evidence indicates that AIF-1 may be associated with various inflammatory conditions and atherosclerosisat the level of cellular expression.
The participation of AIF-1 in inflammatory status and vascular processes implies that AIF-1 may play a role in endothelial dysfunction,macrophages and VSMCs activation, migration, reorganization and tissue remodelling as a response to endothelial damage.
In vitro studies also show that AIF-1 promotes chemotaxis, cell attachment, spreading and migration ofmacrophages and VSMCs which suggest a role of AIF-1 in the atherosclerotic plaque formation. These in vitro studies are supported by immunohistochemical analysis which has shown in vivo protein expression of AIF-1 in human VSMCs in atherosclerotic plaques.
Diabetes mellitus (DM) is a powerful and independent risk factor for cardiovascular disease which remains to be the major cause of death in type 2 diabetic patients.Chronic perturbation of the vasculature, caused by diabetes, leads to increased incidence, size, and complexity of atherosclerotic plaques. Furthermore lesion instability are enhanced in diabetes, and mediate increased incidence and severity of clinical events, such as heart attacks and strokes.The present study aimed at evaluatingrole of serum AIF-1in type 2 diabetic patients in relation to atherosclerosis.
Eighty subjects were recruited in this study divided into two groups; twenty apparently healthy volunteers as a control group , sixty diabeticatherosclerotic patients.
To all studied subjects; thorough history taking was done. Complete physical examination with special stress on BMI calculation,cardiovascular examination and measuring the carotid intima media thickness (CIMT) using a β mode ultrasound.
The following laboratory investigations were done to all participating subjects: quantitation of urinary albumin,urinay proteins and creatinine and calculation of urinary albumin and protein to creatinine ratio, estimation of fasting and postprandial serum glucose, determination of Hemoglobin A1c, estimation of serum urea, creatinine, calculation of estimated glomeruler filtration rate (eGFR), estimation of serum Lipid profile (total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides and calculation of low density lipoprotein cholesterol (LDL-C)) , estimation of serum C-reactive protein (CRP) and estimation of serum AIF-1 by ELISA technique.
In the current study, the meanof HDL-C in diabetic atherosclerotic group (group 2) was significantly lower than the control group (p=0.000). the meanof TG and LDL level in diabetic atherosclerotic group were significantly higher than the control group (p=0.000).Also, there was a significant increase in BP in the diabetic atheroscleroticpatients (p=0.004) as compared to controls.
When diabetes is accompanied by other major cardiovascular risk factors such as hypertension, dyslipidemia, and smoking the incidence of atheroscelerosis is markedly increased.
In this study, the CIMT was significantly higher in the group of diabetic atherosclerotic group when compared to the control group (p=0.000).
Carotid-wall intima–media thickness is a surrogate measure of atherosclerosis associated with cardiovascular risk factors and with cardiovascular outcomes.
Results of the present work revealed that the levelof AIF-1 was significantly higher in the diabetic atherosclerotic group when compared to the control group(p=0.000),Also, there was a significant positive correlation between CIMT and AIF-1 (r=0.468, p= 0.000) in the group of diabetic atheroscleroticpatients .
In the present study the level of HbA1c was significantly higher in diabetic atheroscleroticpatients (group 2) when compared to the control group , (p=0.000).
Also, there was a significant positive correlation between CIMT and HbA1c (r=0.257, p= 0.047) in the group of diabetic atheroscleroticpatients ,that suggested that poor glycemic control is associated with structural changes in the carotid artery that are consistent with early atherosclerosis.
In the present work,by drawing receiver operating characteristic (ROC)in the studied groups,the area under the curve (AUC) for AIF-1 was 0.843, p=<0.0001.
The sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of AIF-1 as a marker of atherosclerosis at a cutoff value of 120 pg/ml were 98.33%, 70%, 91%, 93% and 91%respectively.
from the previous results it can be noticed that AIF-1 can be used as a helpful marker for detection of atherosclerosis and prediction of cardiovascular complications in type 2 diabetic patients.