الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Diabetes mellitus is a metabolic disorder of multiple causes which is characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism.
Long-term hyperglycemia can lead to severe complications later in life. These complications of diabetes are divided into macrovascular and microvascular complications.
Diabetic nephropathy (DN) is one of the most important microvascular complications associated with type 2 diabetic patients and has emerged as a leading cause of the end-stage renal disease in developed countries. DN is characterized by structural abnormalities of kidney including hypertrophy of both glomerular and tubular elements, increase in the thickness of glomerular basement membranes, and progressive accumulation of extracellular matrix components, eventually leading to proteinuria and renal failure. Despite implementation of intensive glycemic and antihypertensive control, DN remains an important clinical problem.
It is known that tubulointerstitial damage plays an important role in diabetic nephropathy. Therefore, it would potentially be beneficial if albuminuria, as a marker of glomerular damage, could be supplemented by a marker of tubular damage to provide a more complete status of the kidney injury. This could help us first to more accurately predict the patients at risk of developing diabetic nephropathy and second to provide a better and possibly different treatment for diabetic nephropathy.
Liver-type fatty acid-binding protein (LFABP) is an intracellular carrier protein that is expressed in the proximal tubules in the human kidney and participates in fatty acid metabolism .In one clinical study, urinary excretion of L-FABP was reported to offer potential as a clinical marker to screen for kidney dysfunction and thereby to identify patients who are likely to experience deterioration of renal function in the future.
However, not all patients with diabetes-mediated hyperglycemia will develop this disease .It appears that both environmental and genetic factors play a role in the development of diabetic nephropathy, making diabetic nephropathy a complex disease. Thus, a major goal is to better understand the risk factors, including common genetic factors, that may influence the outcome of renal disease, with hope for better identification of susceptible individuals who might benefit from appropriate treatment.
One putative genetic determinant of diabetic nephropathy is the Pro12Ala (P12A) polymorphism in the gene encoding peroxisome proliferator-activated receptor g (PPARγ). PPARγ, a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors, plays a key role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis. The P12A single-nucleotide polymorphism (SNP) located in the adipocyte-specific PPARγ2 isoform has been associated with greater insulin sensitivity, significantly reduced risk of type 2 diabetes and reduced risk of myocardial infarction.
The present study aimed to evaluate the association between the urinary Liver- Type Fatty Acid–Binding Protein (u-LFABP) and PPARγ2 Pro12Ala polymorphism in a trial to find their association with the occurrence of diabetic nephropathy .
The present study were conducted on 80 subjects categorized as follows:
Group I: 20 diabetic patients with normoalbuminuria (ACR <30).
Group II: 20 diabetic patients with microalbuminuria ( ACR<30-300).
Group III: 20 diabetic patients with macroalbuminuria,( ACR >300).
Control subjects
Comprisied 20 non-diabetic healthy, age-matched subjects as the case groups.
Full clinical examination with special stress on history of the onset of diabetes mellitus and blood pressure measurement.
All of the patients underwent a standardized laboratory evaluation including Fasting and postprandial serum levels of glucose, Glycated hemoglobin (HbA1c). Fasting serum levels of creatinine, urea, uric acid, total cholesterol, high density lipoprotein- cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides (TG)and non esterified fatty acids (NEFA).
Levels of serum and urinary Liver-type Fatty Acid Binding Protein (L-FABP) has been determined, also Pro12Ala mutation in the PPARγ2 gene in blood using polymerase chain reaction /restriction fragment length polymorphismn (PCR/RFLP) technique has been detected.
Our results revealed that U-LFABP levels were significantly higher in the normoalbuminuric group versus the control group and significantly increased according to the severity of diabetic nephropathy.
Serum L-FABP was positively correlated with urinary L-FABP in all studied groups urinary L-FABP levels showed positive significant correlation with, NEFAand ACR.
The current study indicated that the genotypic distribution of the PPARγ2 Pro12Ala gene polymorphism was in Hardy-Weinberg equilibrium. Frequency of Pro allele was significant increase in diabetic nephropathy case subjects (miro and macro albuminuric) when compared to control group. However, there was no difference between normoalbuminuric diabetic group and control group as regard the allelic frequencies, while diabetic macrolbuminic patients had higher Pro allele frequency than in diabetic microalbuminuric patients.
Our data showed that Ala carriers (Ala/Ala and Pro/Ala) had a lower FFAlevel than the Pro/Pro homozygotes patients (P = 0.001) in all studied group
In the present study Our results showed that the level ofU L-FABP was significantly higher in Pro/Ala plus Ala/Ala carriers than subjects with Pro/Pro genotype (i.e., P = 0.001, 0.0021, 0.011, 0.0001 in controls, groups I, II and III, respectively).
There were no differences between Ala carriers (Ala/Ala and Pro/Ala) and noncarriers regarding age, diabetes duration, fasting plasma glucose, HbA1c, and blood pressure levels our data revealed that there were no significant differences in the lipid spectra (TG, CH, HDL-CH, LDL-CH between Ala carriers (Ala/Ala and Pro/Ala) and noncarriers (P>0.05).
Moreover Carriers of the Ala allele had lower serum urea and creatinine than subjects with the Pro/ Pro genotype in different studied groups (p<0.05)