الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Diabetes mellitus (DM) has become a significant health problem in most nations with the number of patients dramatically increasing and expected to reach 366 million by the year 2030.Diabetes-related microvascular disease such as retinopathy and nephropathy are major causes of blindness and renal insufficiency.
Albuminuria is an independent risk factor of rapid progression of chronic kidney diseases (CKDs) and in T2DM considered a warning sign for DKD. The level of urinary albumin excretion has been associated with CVDs in diabetic patients with DKD. Subclinical myocardial dysfunction is even more common than overt heart failure in diabetic patients.
Screening for DN needs to be a routine component of diabetes care. The ADA recommends yearly screening for individuals with type 2 diabetes at the diagnosis and five years after diagnosis of type 1diabetes. Because urinary albumin excretion is recognized as an early predictor of diabetic nephropathy in addition to cardiovascular disease, it has become an important target for screening.
Morphological changes in DN known to start earlier than laboratory abnormality. Also some patient with albuminuria have normal renal structure, while some normoalbuminuric diabetic have well established nephropathic leisons. Also albumin excretion rate is a predictor of renal disease in hypertension and cardiovascular diseases, so it is not a sensitive marker for diabetic nephropathy. Thus, more earlier markers of diabetic nephropathy needed to be identified.
Deregulation of the lipid metabolism with a disturbed free fatty acid (FFA) metabolism is a characteristic of metabolic disorders including type 2 diabetes and obesity and likely contributes to end stage kidney disease irrespective of the underlying kidney disease.
FABP has 10 isoforms that are distinctly distributed in various tissues in mammals and that have distinct mechanisms in different organs and cells. Among them, heart type (H) FABP, also referred to as FABP3, is most predominantly expressed in the heart and less in the skeletal muscle, kidney, stomach and testis. It mediates the passage of fatty acids from the plasma membrane to sites of lipid synthesis.
H-FABP is undetectable in normal conditions but is released rapidly from cardiomyocytes into circulating blood after myocardial cell damage in association to left ventricular hypertrophy and dysfunction with various metabolic abnormalities such as central obesity, dyslipidemia, insulin resistance and T2DM, even in the absence of hypertension.
H FABP expression was significantly higher in proteinuric kidney diseases, including diabetic kidney disease and obesity associated glomerulopathy (ORG) and contributes to Podocyte cell injury. Albuminuria expresses underlying endothelial dysfunction as presence of chronic hyperglycemia cause disruption of the endothelial permeability through production and activation of mediators such as ROS, VEGF and pro inflammatory cytokines. This disturbance of endothelial cell podocyte communication contributes to and amplifies the endothelial lesions with subsequent interstitial fibrosis, and glomeruloscelorosis leading to renal function deterioration.