Human peroxisome proliferator-activated receptor 2 [PPAR 2] pro 12 Ala polymorphism: a possible association with risk of diabetic nephropathy in type 2 diabetes

Mutations of the nuclear receptors PPAR-gamma confer an extreme phenotype of partial lipodystrophy, early-onset severe insulin resistance, type 2 diabetes, dyslipidemia, hypertension, and hepatic steatosis. The association between the Pro 12 Ala polymorphism in PPAR-gamma and obesity, insulin sensitivity, and type 2 diabetes was studied. It appears that the Ala 12 allele confers modest protection against the onset of type 2 diabetes and is also associated with an increased BMI in overweight individuals. This study was conducted to investigate an association between Pro 12 Ala polymorphism and the incidence of diabetic nephropathy in obese patients with long-lasting type 2 diabetes. The study was carried on sixty patients with type 2 diabetes mellitus, they were divided to 2 groups, group 1 included 30 patients with diabetic nephropathy and group 2 include 30 patients without diabetic nephropathy. Thirty healthy subjects of matched age and sex were included as controls [group 3]. Pro 12 Ala polymorphism was statistically significant more frequent in the diabetic group without nephropathy [group 2] in comparison to diabetic patients with nephropathy [group 1] p<0.0001, and the control group [group 3], p<0.0001. but there was no significant difference between the diabetic nephropathy group [group 1] and control group [group 3]. PPAR gamma receptor polymorphism was positive in 7 patients [23.33%] and negative in 23 patients [76.67%] of the diabetic nephropathy group [group 1]. In the diabetic group without diabetic nephropathy, it was positive in 24 patients [80%], negative in 6 patients [20%]. On the other hand, patient with diabetic nephropathy [group 1] associated with hypertension [21 patients] were all negative regarding PPAR gamma Pro 12 Ala polymorphism. Whereas, those without hypertension only 2 out of 9 patient were negative and the remaining 7 cases were positive regarding polymorphism. There were no significant differences between the two diabetic groups of patients regarding BMI, lipid profile and duration of diabetes. There was also no association between PPAR polymorphism and duration of diabetes, BMI and any of the biochemical parameters measured. In conclusion, the presence of the Ala allele of the PPAR gamma Pro 12 Ala polymorphism seems to be associated with a decreased risk of diabetic nephropathy in patients with type 2 diabetes. This association needs to be confirmed in other patient populations. More basic studies will be required to uncover the molecular mechanisms underlying the association between PPAR gamma Pro 12 Ala polymorphism and diabetic nephropathy risk

Clinical implications of markers of apoptosis in patients with myocardial infarction

To examine the possible participation of the Fas/Fas ligand [Fas-L] system and tumor necrosis factor-alpha [TNF-alpha] in the pathogenesis of acute and old myocardial infarction [AMI and OMI] in a trial to explore the role of immune mechanisms in the pathogenesis of these conditions. Serum levels of sFas, sFasL and TNF-alpha were measured in 10 patients with AMI, 12 patients with OMI and 15 normal subjects as control group. We excluded AMI patients with congestive heart failure, concomitant inflammatory disease, cancer or other significant heart diseases. Serum levels of sFas, sFas ligand and TNF-a were determined by ELISA. Serum levels of sFas and TNF-alpha were greater than normal only in patients with AMI compared to normal subjects, however, there was no difference among serum levels of sFasL for all groups. We found that circulating levels of sFas and TNF-alpha in patients with AMI increase during the early phase of disease whereas levels of sFas ligand remained unchanged. Therefore circulating sFas and TNF-a could play an important role as marker of pathophysiologic conditions associated with cardiomyocyte apoptosis in AMI

Plasma endothelin-1 levels in patients with cirrhosis and their relationship to the severity of cirrhosis

This study focused on the possible role of endothelin-1 [ET-1] in the pathogenesis of portal hypertension and also its relation with the degree of liver affection. The plasma levels of ET-1 were measured in 10 healthy control subjects and 80 patients with cirrhosis and they were correlated with various clinical and laboratory parameters. There was a significant elevation of ET-1 in all patients with cirrhosis compared with the control group [14.59 +/- 3.57 pg/ml vs. 4.2 +/- 0.34 pg/ml, respectively]. The highest level of ET-1 was obtained in the group of cirrhotic patients with ascites. Plasma ET-1 levels were significantly elevated in cirrhotic patients with bleeding esophageal varices [12.21 +/- 0.45 pg/ml] compared with those without [10.03 +/- 0.37 pg/ml]. Plasma ET-1 level was positively correlated with total and direct bilirubin, ALT, AST, PT and serum creatinine. The plasma level of ET-1 was negatively correlated with albumin and PC. It was concluded that plasma ET-1 is elevated in liver cirrhosis in a disease stage-dependent manner, which may have diagnostic and prognostic values and may be used as a marker for the progression of the disease

Plasma endothelin-1 levels in patients with type II diabetes mellitus with vascular complications

The aim of this study was to evaluate plasma endothelin-1 [ET-1] levels in patients with non insulin dependent diabetes mellitus [NIDDM] and its relation to the presence of diabetic vascular complications. The study was conducted on 40 patients with NIDDM with fatty liver and divided into 2 groups. Group 2 [G2] consisted of 20 patients with NIDDM associated with hypertension. Group 3 [G3] consisted of 20 patients with NIDDM with various diabetic vascular complications. Twenty of apparently healthy subjects, age and sex matched, served as a control group [G1]. The results showed that the plasma ET-1 concentration was significantly highly increased in the two patients' groups compared with the control group and was significantly highly increased in group 2 compared with group 3. Plasma ET-1 was positively correlated with the duration of diabetes mellitus, fasting blood glucose, postprandial blood glucose, triglyceride, total cholesterol, low density lipoprotein and serum urea and negatively correlated with high density lipoprotein. It was concluded that ET-1 might represent a new marker of diabetes related vascular damage