Angiotensin converting polymorphism in obese patients

Obesity is a complex disorder caused by the interaction of environmental and genetic susceptibility associated with increased risk of morbidity from a variety of disorders. The aim of the present study was to investigate the association between ACE I/D polymorphism and obesity and its contribution to the different risk factors among obese patients which may constitute the basis for strategies to manage this serious problem. Fifty-four male obese patients with BMI >/= 30 kg/m[2] were recruited. Twenty-six healthy men with BMI < 25 kg/m[2] of comparable age were selected as a control group. All patients and controls were subjected to thorough history taking, anthropometric measurements [weight, height, BMI, waist and hip circumference and WHR] and BP measurement. ECG was done. Laboratory investigations included FPG, PPPG, HbA[1c], OGTT, lipid profile and fasting serum insulin. IR was determined by the computer updated 1996 version of HOMA2. ACE I/D polymorphism was determined by PCR. Eighteen and a half percent of obese patients had a family history of CHD and 31.5% were smokers. Nineteen patients were categorized as prehypertensives while 20 had stage 1 or stage 2 hypertension. IHD was diagnosed in five obese patients. Hyperlipidemia, IGT and DM were detected in 61.1%, 50% and 22.2% of obese patients, respectively; 29.6% of patients had grade I obesity, 29.6% had grade II and 40.7% had grade III obesity. Sixty-three percent of patients had a waist circumference> 102 cm and 38.9% had a WHR> 1.0. Obese patients had significantly higher FPG, PPPG, HbA[1c], fasting serum insulin, HOMA2-IR and HOMA2-%B as compared to controls. On the other hand, HOMA2-% S was significantly lower in obese patients. All studied lipid parameters were significantly higher in obese patients except HDL-cholesterol which was significantly lower in obese patients. The distribution of the ACE genotype for obese patients was 38.9%, 46.3% and 14.8%, for the DD, ID and II, respectively. In controls, 34.6% were DD, 46.2% were ID and 19.2% were II genotype. There was no statistically significant difference between obese patients and controls as regards the genotype frequency [Pearson X[2]=0.296; P=0.862]. Relative allele frequencies in both groups were D allele: 0.620 in obese versus 0.577 in controls and I allele: 0.380 versus 0.423, respectively with no statistically significant difference as well. There was a statistically significant difference between the three ACE I/D genotypes of obese patients as regards BMI, waist circumference and WHR. The DD genotype was associated with higher values of these obesity markers. No such differences were observed for control participants. There were no significant differences in age, SBP and DBP among the three ACE genotypes of obese patients. However, there was a tendency towards DD genotype in the older age group and in patients with higher BP. There was no significant difference between DD, ID and II ACE genotypes of obese patients as regards any of the studied metabolic parameters. However, numerically higher values of FPG, PPPG, HbA[1c], fasting serum insulin, HOMA2-IR, serum triglycerides, total cholesterol and LDL-C and lower values of HOMA2-%S and HDL-cholesterol were observed among DD genotypic obese patients. Overall, DD homozygote obese patients showed a tendency for family history of CHD, smoking, abdominal adiposity, hypertension, hyperlipidemia and DM. ACE I/D polymorphism was significantly associated with abdominal adiposity, hyperlipidemia and DM in obese patients when compared with patients having no such risk factors [P=0.021, P=0.049, P=0.045, respectively]. Nine obese patients showed a maximum of five associated risk factors that were added to obesity, while only two obese patients presented with no such associated risk factors at all. Seven of those nine obese patients were DD homozygotes. It was found that the more the number of studied risk factors added to obesity, the more the prevalence of the DD homozygote genotype [LLR=27.153; P=0.002]. The results of the present study could indirectly suggest that the DD genotype contributes a genetic factor for the development of abdominal obesity and that this would predispose obese patients to further risk for development of CHD. ACE inhibitor therapy can induce improvements in atherosclerosis and IR and therefore they are ideal drugs to be used in obese hypertensive patients

Bone metabolism in dialysis patients assessed by biochemical markers and densitometry

A decrease in bone mineral density is common in patients with chronic renal failure. It is also a risk factor for fractures in this population. The aim of the study was to evaluate bone mineral density-BMD and some biochemical markers of bone metabolism in patients on chronic hemodialysis. The study was performed on 50 patients on chronic hemodialysis. Bone mineral density was measured using dual energy x-ray absorptiometry [DEXA] in the distal left forearm. Concentrations of iPTH and carboxy terminal propeptide of type I collagen [PICP] was measured by commercially available Kits. Mean T scores of the distal left forearm were -2.7 +/- 2.2 for men and -2.2 +/- 1.9 for women T scores in the range of osteopenia were present in 30% of patients, and in the osteoporosis range in 54% of patients. Patients with bone mass measurements in the osteoporosis range had significantly increased iPTH levels compared with patients with T scores in the osteopenic/normal range. There was statistically significant negative correlation between BMD T scores and iPTH [r=-0.63, P0.0032] and with PICP [r=-0.820, P=0.0001]. On the basis of our finding we conclude that bone loss is seen in patients on chronic hemodialysis. Bone turnover markers estimated in this population correlated well with BMD measurements at sites of pure cortical bone as the distal radius

Cytokine elimination during continuous hemofiltration. A feasible clinical modality for septic patients

Tumour necrosis factor a [TNF-alpha] and interleukin 6 [IL-6] arc important prognostic markers in intensive care unit [ICU] septic patients. The aim of the study was to determine whether continuous venovenous hemofiltration [CVVH]. using Fresenius hemofilter AV600s, leads to elimination of TNF-alpha and IL-6 in 20 septic patients with multi-organ failure. At the start of hemofiltration [o], 6 and 12 hours the mean afferent plasma concentration +/- SD of TNF-alpha [41.9 +/- 9.56, 30.85 +/- 6.2. 25.5 +/- 5.28 pg/ml] and that of IL-6 [890 +/- 183.96, 635 +/- 149.65, 410 +/- 168.27, pg/ml]. 'the different plasma concentrations were significantly lower than tile corresponding afferent concentrations. TNF-alpha and IL-6 were detectable in the ultra filtrate of all patients. The plasma clearance of TNF-alpha and IL-6 significantly decreased after 12 hours as a result of the adsorptive elimination of the mediators due to progressive membrane saturation. We demonstrated that CVVH could represent an appropriate tool to remove a broad spectrum of proinflammatory mediators, if such removal is required in septic patients

Plasma total homocysteine levels in patients with tType 1 diabetes: effect of chronic cigarette smoking

Aim: The purpose of this study was to compare plasma total homocysteine [tHcy] levels, a recognized cardiovascular risk factor, in non-diabetic subjects and type 1 diabetic patients, and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma tHcy levels in these patients. Subjects and To achieve this aim, plasma tHcy concentrations were measured in 50 young type 1 diabetic patients without clinical evidence of macroangiopathy and in 50 healthy control subjects who were matched for age, sex, BMI and smoking habit. It was found that plasma tHcy levels were significantly higher in type 1 diabetic patients than in control subjects [12.5 +/- 4.9 vs 10.3 +/- 2.3micro mol/l, P<0.01]. Comparing the clinical and biochemical characteristics of diabetic subjects grouped according to smoking status, diabetic smokers had higher levels of plasma triglycerides, but no significant differences were found in age, sex, BMI, total cholesterol, creatinine, glycometabolic control, blood pressure, duration of diabetes, and the presence of chronic microvascular complications. Nevertheless, plasma tHcy levels were markedly elevated in diabetic smokers [by -50%] versus nonsmokers, [15.5 +/- 5.6 vs 10.6 +/- 2.9 micro mol/l, P<0.0001] in a dose-dependent fashion, when subjects were categorized for the number of cigarettes smoked daily. Conclusions: We concluded that chronic cigarette smoking seems to adversely affect plasma tHcy levels in young adults with type 1 diabetes

Matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, parathyroid hormone related protein and tissue expression of CD44v6 in metastatic breast cancer

Matrix metalloproteinases [MMPs] and their inhibitors [TIMPs] modulate ECM composition and may affect breast cancer invasion and metastases. Bone metastases are a frequent complication of advanced breast cancer. This work investigated the relationship between plasma levels of MMP-9, TIMP1, PTHrP, tissue expression of CD44v6 and the development of nodal and bone metastases in 40 female patients with different stages of breast cancer. The control group comprised 10 females with benign breast lesions. All studied parameters were significantly higher in patients than in controls. Patients with lymph node involvement has significantly higher plasma MMP-9, MMP9/TIMP-1 ratio and CD44c6 expression than those without nodal affection, [p= 0.018, 0.006 and 0.02 respectively]. Higher MMP-9 MMP9/TIMP-1 ratio and PTHrP were found in patients with than those without bone metastases [p = 0.013, 0.01 and 0.0002 respectively]. CD44v6 expression was associated with increased MMP-9 and TIMP-1 levels as well as higher tumour grade. Post-operative MMP-9 was significantly lower than pre-operatively. Our data indicate that increased plasma MMP-9 and MMP-9 / TIMP-1 imbalance may be useful markers for development of nodal and bone meatstases in breast cancer patients and in predicting post-operative recurrence. While CD44v6 is involved in nodal metastases, PTHrP seems to be an important determinant of development of bone secondaries

Acute effects of somatostatin injection on glucorgulation in states of hyperinsulinemia

Aim: Hyperinsulinemia is a constant feature of insulin resistant states. Insulin resistance appears to be a syndrome that is associated with type 2 diabetes mellitus, obesity, hypertension, lipid abnormalities and atherosclerotic cardiovascular disease. This study aimed at studying the effects of insulin suppression in hyperinsulinemic states regarding glucoregulation. Thirty patients were allocated in three groups: GIII: Obese nondiabetic [n =10], GIl: lean essential hypertensive patients [n =10], and Gill: obese type 2 diabetic patients [n =10]; together with 10 normal individuals as control. All cases were subjected to measurement of BMI, blood pressure, serum insulin and whole venous blood glucose fasting and after 60 minutes interval for 3 hours after 100 micro g subcutaneous injection of long acting somatostatin analogue. Fasting hyperinsulinemia was found in 80% of obese non-diabetics; 60% of lean essential hypertensive patients and in 90% of obese type 2 diabetic patients. Hyperinsulinem was positively correlated with the degree of BMI in group I and III. Maximal percentage suppression of insulin Was inversely correlated with BMI in the three different group. Blood glucose levels were significantly elevated in the second and third hours following somatostatin analogue injection in obese nondiabetic and lean hypertensive groups. Meanwhile it decreased significantly during the whole three hours in obese type 2 diabetic patients. Conclusions: One can conclude that suppression insulin by somatostatin analogue has significant effects on glucose regulation in patients with hyperinsulinemia. These effects were of dubious biological importance

Role of the kidney in removing circulating leptin in humans

To assess the role of the kidney in removing circulating leptin in humans by studying the leptin metabolism across the renal bed of normal human kidney and also studying the circulating leptin levels in end stage renal disease [ESRD] patients maintained on hemodialysis [HD]. The study included 14 human subjects with intact renal functions and who were scheduled for elective cardiac catheterization. Aortic, renal vein, peripherial arterial and urine samples were withdrawn from each subject. A separate cohort of 32 patients with ESRD maintained on HD were also included in the study. A blood sample was taken from the arterial limb of the vascular access of each patient before and after the HD session. For all samples, leptin levels were determined by radioimmunoassay [RIA]. In subjects with intact renal functions, plasma leptin concentrations were significantly increased in the aorta than in the renal vein [11.3 +/- 3.1 vs. 10.1 +/- 2.9 ng/ml] indicating net renal leptin uptake [RU]. The calculated RU was 849 +/- 184 ng/min which accounted for 65% of all leptin removed from the circulation. The calculated renal leptin fractional extraction [Fx] was 15.6 +/- 2%. Lineweaver-Burk analysis indicated that RU followed saturation kinetics with an apparent Michaelis-Menten constant of 10.7ng/ml and maximal velocity of 1700 ng/min. Leptin was generally undetectable in urine. In ESRD patients on HD, the peripheral arterial leptin levels standardized for body mass index were increased by fourfold as compared to control subjects with intact renal function. In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Human kidney plays a substantial role in leptin removal from the circulation by taking up and degrading the peptide. ESRD patients have higher levels of circulating leptin which are not cleared by hemodialysis using modified cellulose membrane