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Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes mellitus, and dyslipidemia. It is well known that the presence of visceral fat increases the risk for metabolic complications of obesity, especially... more
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes mellitus, and dyslipidemia. It is well known that the presence of visceral fat increases the risk for metabolic complications of obesity, especially NAFLD. The visceral adiposity index (VAI), a novel marker of visceral fat dysfunction, shows a strong association with insulin resistance and also cardiovascular and cerebrovascular events. However, there is conflicting data regarding the association between VAI and NAFLD. Our aim was to assess the relationship between VAI, insulin resistance, adipocytokines, and liver histology, in nondiabetic subjects with NAFLD. A total of 215 male patients with biopsy-proven NAFLD were included. Among this group, serum levels of adiponectin, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were measured in 101 patients whose blood samples were available. High gamma-glutamyl transferase (GGT), high total cholestero...
Patients with hypogonadism have poor cardiovascular and metabolic outcomes, and the effect of testosterone replacement therapy (TRT) is not clear. We investigated the presence of inflammation, insulin resistance and endothelial... more
Patients with hypogonadism have poor cardiovascular and metabolic outcomes, and the effect of testosterone replacement therapy (TRT) is not clear. We investigated the presence of inflammation, insulin resistance and endothelial dysfunction in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and the effect of TRT on these subjects. A total of 60 patients with CHH (mean age 21.82±2.22 years) and 70 healthy control subjects (mean age 21.32±1.13 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), TNF-like weak inducer of apoptosis (TWEAK), high sensitive C reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured before and after TRT. The patients had higher Waist Circumferences (WC) (p=0.009), Diastolic Blood Pressures (p=0.02), Triglycerides (p=0.03), ADMA, insulin and HOMA-IR levels (p<0.001 for all) and lower TWEAK levels (p<0.001), compared to the healthy controls. After 5.56±2.04 months of TRT, the patients had significantly elevated systolic blood pressures (p=0.01), body mass indexes and WC (p<0.001 and p=0.001 respectively) and decreased total and HDL cholesterol levels (p=0.032 and p<0.001 respectively). ADMA levels significantly increased (p=0.003), while the alterations in TWEAK, hsCRP and HOMA-IR were not significant. The results of the present study show that endothelial dysfunction, inflammation and insulin resistance are prevalent even in the very young subjects with CHH, who have no metabolic or cardiac problems at present. This increased cardiometabolic risk however, do not improve but even get worse after six months of TRT. Long term follow-up studies are warranted to investigate the unfavorable cardiometabolic effects of TRT.
Objective. The waist circumference (WC) cutoff levels defined for the Caucasian people may not be representative for different ethnic groups. We determined sex specific WC cutoff points to predict obesity, metabolic syndrome, and... more
Objective. The waist circumference (WC) cutoff levels defined for the Caucasian people may not be representative for different ethnic groups. We determined sex specific WC cutoff points to predict obesity, metabolic syndrome, and cardiovascular risk in Turkish adults. Design and Methods. The demographic characteristics of 1898 adult males and 2308 nonpregnant females from 24 provinces of 7 different regions of Turkey (mean age 47 ± 14 yrs) were evaluated. Results. The WC levels of 90 cm and 100 cm define overweight and obese males while the levels of 80 cm and 90 cm define overweight and obese females. With these cutoff values, 239 additional males (12.6%) are diagnosed as overweight and 148 additional males (7.8%) as obese. Instead, 120 females (5.1%) are free of being labeled as obese. Conclusions. This is the first nationwide study to show the action levels of WC for overweight and obese Turkish adults. The ideal cutoff levels of WC to predict metabolic syndrome are 90 cm and 80 ...
Smoking is closely associated with insulin resistance, though the mechanism is not clear. Adiponectin, a novel anti-atherosclerotic and anti-inflammatory adipose tissue product, which is closely associated with insulin resistance, was... more
Smoking is closely associated with insulin resistance, though the mechanism is not clear. Adiponectin, a novel anti-atherosclerotic and anti-inflammatory adipose tissue product, which is closely associated with insulin resistance, was reported to be low in smokers with cofactors for atherosclerosis. However, the effects of smoking on circulating adiponectin levels in otherwise healthy people are unknown. In this study, a case control design was implemented to search for the effect of smoking on plasma adiponectin and insulin sensitivities in healthy people. Sixty-four healthy male smokers, with no family history of hypertension and diabetes mellitus were compared with appropriate 36 age and body mass index matched controls. Both the patients and controls were the soldiers of a troop with regular daily physical activity. Plasma adiponectin, high sensitive C-reactive protein (hsCRP), insulin and lipid levels, and insulin sensitivity as assessed by homeostasis model assessment index (H...
The role of reversibility of nontraditional risk factors, like inflammation and CKD-mineral bone disorder, in the reduction of cardiovascular risk after renal transplantation is still scarcely defined. The longitudinal relationship... more
The role of reversibility of nontraditional risk factors, like inflammation and CKD-mineral bone disorder, in the reduction of cardiovascular risk after renal transplantation is still scarcely defined. The longitudinal relationship between C-reactive protein, CKD-mineral bone disorder biomarkers, and intima media thickness was investigated in a series of 178 patients (age=32±10 years) with stage 5 CKD maintained on chronic dialysis who underwent echo-color Doppler studies of the carotid arteries before and after renal transplantation. Smokers and patients with diabetes were excluded from the study. In all patients, immunosuppression was performed by a standard regimen on the basis of calcineurin inhibitors. Healthy controls were specifically selected to match the age and sex distribution of the patients. Biochemical and intima media thickness assessments were repeated 6 months after transplantation. Before transplantation, intima media thickness in patients with stage 5 CKD on dialy...
Hemoglobin (Hb) regulates the endothelial function by modulating the bio-availability of NO at the tissue level. A significant direct relationship is present between the Hb levels and endothelial functions in patients with Type 2... more
Hemoglobin (Hb) regulates the endothelial function by modulating the bio-availability of NO at the tissue level. A significant direct relationship is present between the Hb levels and endothelial functions in patients with Type 2 diabetes. Testing whether this association also exists in subjects with prediabetes is important because prediabetes is associated with an increased risk of cardiovascular disease and mortality. Therefore, we investigated the association of Hb both with the classical cardiac risk factors and the markers for endothelial dysfunction and inflammation, in subjects with impaired glucose tolerance (IGT). We enrolled 69 normotensive, and cardiovascular events free subjects with IGT (M=40, age=45.50+/-6.8 yr). Plasma insulin, hsCRP, soluble CD40L, vonWillebrand factor, p-selectin levels were measured. The parameters given according to the higher and lower median Hb values of the subjects were compared. Subjects with the higher Hb levels exhibited lower HDL-C (46.68...
Özet: Araştirmanin amaci, Aydin il merkezinde doğum öncesi bakim (DÖB) hizmetlerini nicelik ve nitelik olarak değerlendirmektir. Araştirma kesitsel tiptedir. Aydin merkezinde yaşayan 195 kadin (gebe/lohusa) araştirmaya katilmiştir.... more
Özet: Araştirmanin amaci, Aydin il merkezinde doğum öncesi bakim (DÖB) hizmetlerini nicelik ve nitelik olarak değerlendirmektir. Araştirma kesitsel tiptedir. Aydin merkezinde yaşayan 195 kadin (gebe/lohusa) araştirmaya katilmiştir. Kadinlar, il merkezindeki 10 sağlik ocağindan, (her bir sağlik ocağindan bir kirsal ve bir kentsel sağlik evi olacak şekilde) basit rastgele ve küme örneklem metoduyla seçilmiştir. Veri yüz yüze anket yöntemiyle toplanmiştir. Türkiye
Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We... more
Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessed and ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Card...
CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes... more
CD40 ligand interaction with its receptor (CD40) not only mediates lymphocyte communication, but also associates with chronic inflammation and atherothrombosis. High soluble CD40L (sCD40L) levels were reported in dyslipidemia, diabetes mellitus, and coronary disease. So far, there are no data about sCD40L levels in hypertension. We investigated sCD40L and high sensitive C reactive protein (hsCRP) levels in 30 nonobese young hypertensive men and 30 matched controls. sCD40L and hsCRP levels were not different, and there were no correlations between blood pressure and sCD40L or hsCRP levels. These results might indicate lack of any inflammatory state in new onset hypertension.
Endothelial dysfunction (ED) has a major role in the cardiovascular outcome of patients with chronic kidney disease (CKD). The aim of this study was to investigate the relation between fetuin A levels and ED in kidney transplant... more
Endothelial dysfunction (ED) has a major role in the cardiovascular outcome of patients with chronic kidney disease (CKD). The aim of this study was to investigate the relation between fetuin A levels and ED in kidney transplant recipients. Forty-two living donor kidney transplant recipients, 21 (11 male) on cyclosporine A and 21 (10 male) on tacrolimus-based regimes, were studied. Forty-two (21 male) healthy subjects were enrolled as controls. Fetuin A, highly sensitive C-reactive protein (hsCRP) levels, brachial artery endothelium-dependent vasodilatation (FMD), nitroglycerine mediated dilatation (NMD), and carotid intima-media thickness (CIMT) were measured before transplantation and on the 30th and 90th days posttransplant. Pretransplantation serum fetuin A concentrations and FMD values of patients were significantly lower than those of the controls (P<0.001 for both). These were significantly increased in the 30th and 90th days posttransplantation There was a significant positive correlation between Fetuin A and FMD levels both before and after kidney transplantation (r=0.534, r=0.576; respectively, P<0.001 for both). Carotid intima-media thickness and hsCRP levels decreased after transplantation (P<0.001 for all). According to the regression analysis, fetuin A, intact parathyroid hormone, and hsCRP levels were the independent determinants of FMD. The results of the present study suggest that low serum fetuin A levels in CKD may contribute to impaired endothelial functions in CKD. Future studies should clarify the role of fetuin A levels in cardiovascular outcomes of CKD.
Oxidative stress plays a role in the mechanism of chronic kidney disease (CKD), and antioxidant regimes are regarded as promising treatment modalities. We compared the effects of cilazapril, simvastatin, and hyperbaric oxygen (HBO)... more
Oxidative stress plays a role in the mechanism of chronic kidney disease (CKD), and antioxidant regimes are regarded as promising treatment modalities. We compared the effects of cilazapril, simvastatin, and hyperbaric oxygen (HBO) treatment on proteinuria and on oxidative stress in adriamycine (ADR)-induced proteinuria. Seventy male Sprague-Dawley rats were housed, and 60 were injected with ADR to induce nephrosis. After the stabilization of proteinuria, rats were treated for 6 weeks with simvastatin (n = 10, 4 mg/kg/day), cilazapril (n = 10, 10 mg/kg/day), HBO (n = 10, 2.8 athmosphere absolute, 90 min/daily), HBO + cilazapril (n = 10), HBO + simvastatin (n = 10), and vehicle (n = 10). After euthanization at 12 weeks, protein carbonyl (PCO), superoxide dismutase (SOD), and glutathion peroxidase (GPx) levels were analyzed from tissues. The histological alterations in the kidneys were determined by semiquantitative scoring. Protein carbonyl (PCO) levels were higher (p < 0.001), and the GPx and SOD levels were lower (p < 0.001 for all) in the nephrotic rats. Proteinuria was correlated to PCO (r = 0.483), GPx (r = -0.686), or SOD (r = -0.620) (p < 0.001 for all). Superoxide dismutase (SOD) (beta = -0.381, p = 0.02) and GPx (beta = -0.509, p < 0.001) were independently related to proteinuria levels. Both cilazapril and simvastatin significantly improved GPx, SOD, PCO, and proteinuria. When HBO was combined with either drug, the above markers further improved (p < 0.001). Both regimens caused distinct histological features, while the combination of HBO made much significant histological improvement. Both cilazapril and simvastatin regimens improve oxidative stress and proteinuria, while the effects significantly increase with the combination of HBO treatment. HBO seems to be a candidate antioxidant strategy in glomerular diseases.
Diabetic nephropathy (DN) is a major manifestation of microangiopathy in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major... more
Diabetic nephropathy (DN) is a major manifestation of microangiopathy in patients with Diabetes Mellitus (DM). Inflammation is one of the major factors in the formation of endothelial dysfunction. Endothelial dysfunction is a major contributor to the complications of DM. The aim of the present study was to investigate the possible relationship between inflammation, endothelial dysfunction and proteinuria in patients with diabetic nephropathy. Plasma TNF-α and IL-6, pro-inflammatory cytokines, concentrations were measured in 25 patients with DN and in 30 diabetic control subjects. Also, we evaluated the markers of endothelial dysfunction such as flow mediated dilatation (FMD), nitrate-mediated dilatation (NMD) and carotid intima-media thickness (CIMT). TNF-α, IL-6 and high-sensitivity C-reactive protein concentrations were significantly higher (p = 0.012, p = 0.006 and p < 0.001, respectively) in the patients with DN than the controls. And, urinary protein concentrations were significantly higher (p < 0.001) but eGFR levels were significantly lower (p < 0.001) in the patients with DN. FMD was significantly lower in DN patients (p < 0.001). We have observed that FMD correlated negatively with body mass index (r = -0.424, p < 0.05). And there was also a positive correlation between TNF-α and urinary protein concentrations in the patients with DN (p < 0.05). TNF-α, IL-6, hsCRP and urinary protein concentrations are higher in the DN patients. There were no correlations among pro-inflammatory cytokines concentrations and markers of vascular endotelial disfunction. These findings did not show vascular endothelial dysfunction, but may indicate glomerular endothelial dysfunction.
Adiponectin appears to be an important modulator for metabolic and vascular diseases. A case-controlled study was designed to measure plasma adiponectin levels and investigate the effects of rosiglitazone on adiponectin levels in type 2... more
Adiponectin appears to be an important modulator for metabolic and vascular diseases. A case-controlled study was designed to measure plasma adiponectin levels and investigate the effects of rosiglitazone on adiponectin levels in type 2 diabetic patients with proteinuria. Sixty-four patients (mean age, 46.1±4.6 yr; 30 male, 34 female) and 26 healthy volunteers (mean age, 45.3±4.8 yr; 14 male, 12 female)
Previous studies have demonstrated that elevated plasma leptin concentrations are associated with essential hypertension. It has also recently been shown that leptin plays a promoting role in angiogenesis, and the vascular endothelium... more
Previous studies have demonstrated that elevated plasma leptin concentrations are associated with essential hypertension. It has also recently been shown that leptin plays a promoting role in angiogenesis, and the vascular endothelium expresses the long form of leptin receptor. Those data led us to hypothesize that leptin might contribute to end-organ damage in hypertension. Thus, in the present study we evaluated the relationship between plasma leptin concentrations and hypertensive retinopathy (HR). One hundred and eleven patients newly diagnosed with essential hypertension [EHT; mean age, 43.5 +/-10.7 yr; body mass index (BMI), 28.1 +/- 4.4 kg/m2; male/female ratio, 71/40] and 79 healthy normotensive control subjects (NT; mean age, 43.6 +/- 9.2 yr; BMI, 28.2 +/- 3.3 kg/m2; male/female ratio, 50/29) were enrolled in the study. For the assessment of retinopathy according to the Keith-Wagener classification, direct and indirect ophthalmoscopy were performed in all subjects after dilatation of the pupils. Plasma leptin levels were significantly higher in EHT (11.8 +/- 11.1 ng/mL) than in NT (7.2 +/- 5.1 ng/mL) (P = 0.003). Plasma leptin concentrations were strongly correlated with BMI in both EHT (r = 0.45; P = 0.001) and NT (r = 0.38; P = 0.001) groups. Plasma leptin in patients with grade 2 HR (24.8 +/- 15.8 ng/mL; n = 22) was significantly higher than that in patients with grade 1 HR (16.1 +/- 4.9 ng/mL; n = 29; P = 0.001), grade 0 HR (5.1 +/- 3.1 ng/mL; n = 60; P = 0.001), and NT (P = 0.001). Plasma leptin in patients with grade 1 HR was also significantly higher than that in patients without retinopathy (P = 0.001) or in NT (P = 0.001). The estimated threshold of plasma leptin concentration for HR was 10.2 ng/mL. This critical leptin level served largely to separate patients with retinopathy from those without retinopathy. In summary, our results show that plasma leptin concentrations increase progressively with higher grades of hypertensive retinopathy even after correction for BMI, suggesting that a critical leptin level is needed for the development of retinopathy. Elevated concentrations of plasma leptin might be secondary to release of leptin by the vascular endothelium damaged by high blood pressure, as an epiphenomenon. However, a pathogenic role for leptin in hypertensive retinopathy cannot be excluded.
Prediabetes has been associated with an increased risk of cardiovascular disease and mortality. Soluble P-selectin (sP-selectin) is an index of platelet activation and also a risk factor for future vascular events. sP-selectin levels were... more
Prediabetes has been associated with an increased risk of cardiovascular disease and mortality. Soluble P-selectin (sP-selectin) is an index of platelet activation and also a risk factor for future vascular events. sP-selectin levels were investigated in prediabetic subjects who had no confounding factors such as hypertension, obesity or dyslipidaemia. sP-selectin, hsCRP levels and HOMA-IR indexes were measured in 40 prediabetic subjects (n = 24 for IFG and n = 16 for IGT) and age-, sex- and BMI-matched 40 healthy controls. sP-selectin levels in prediabetic subjects were not significantly different compared with those in controls (p = 0.12). Prediabetic group had similar hsCRP (p = 0.29), higher HOMA-IR indexes (p < 0.001) and lower HDL cholesterol levels (p = 0.001) when compared with healthy controls. The power of the study was 0.93 for sP-selectin, 0.7 for hsCRP and 1.0 for HOMA. Our data suggest that sP-selectin may not contribute to the prothrombotic state as well as the accelerated atherogenesis associated with prediabetes.
Previous studies demonstrated elevated plasma leptin and angiotensinogen (PRA) levels in essential hypertension. However, a few studies investigated the relationship between leptin and angiotensinogen levels in both lean and overweight/... more
Previous studies demonstrated elevated plasma leptin and angiotensinogen (PRA) levels in essential hypertension. However, a few studies investigated the relationship between leptin and angiotensinogen levels in both lean and overweight/ obese hypertensives. The aim of the present study was therefore to examine the relationship between blood pressure, leptin and plasma renin activity in normotensives and in both lean and overweight/obese patients with essential hypertension. Two groups of subjects who were carefully matched for age, gender, waist:hip ratio and body mass index (BMI) were studied: 28 normotensives (NT) (age: 40.1+/-9.1 years old, BMI: 28.1+/-3.6 kg/m2, male/female: 18/10) and 33 newly diagnosed mild to moderate essential hypertensives (EHT) (age: 38.9+/-10 years old, BMI: 27.9+/-4.8 kg/m2, male/female: 22/11). No significant differences in age, gender, waist:hip ratio, fasting blood glucose and BMI were detected between EHT and NT groups. However, systolic and diastolic pressures, mean arterial blood pressures, plasma leptin levels and PRA were significantly higher in EHT group than in NT group (P = 0.001). Plasma leptin levels were strongly correlated with BMI in EHT (r=0.67, P = 0.001) and NT groups (r=0.44, P = 0.001). Plasma leptin levels were correlated with plasma PRA levels in both EHT and NT groups (r = 0.66 and r = 0.44; both P < 0.05, respectively). There was no correlation between leptin or PRA and systolic, diastolic pressures, or mean arterial blood pressures. Furthermore, the patients were divided as lean (n=16) and overweight/obese (n = 17) and compared with BMI-matched controls. In both subgroups, plasma leptin and PRA levels were also higher than those of controls. Our results showed that elevated plasma leptin and PRA are associated with hypertension in both lean and overweight/obese hypertensives. Moreover, plasma leptin was significantly correlated with plasma angiotensinogen levels. These findings suggest that adipose mass is an important determinant of blood pressure, although the mechanism is not clear.
Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low grade inflammation has been reported to participate in the pathogenesis of insulin resistance. Chitotriosidase (ChT), a protein secreted by activated... more
Polycystic ovary syndrome (PCOS) is characterized by insulin resistance. Chronic low grade inflammation has been reported to participate in the pathogenesis of insulin resistance. Chitotriosidase (ChT), a protein secreted by activated macrophages, has been shown to be involved in chronic inflammatory responses. In the present study, serum chitotriosidase activity and its relationship with insulin resistance were determined in patients with PCOS.34 patients with PCOS and 44 age and body mass index (BMI) matched healthy controls were enrolled in the study. ChT activity was measured by the fluorescence method. High sensitivity C reactive protein (hs-CRP) and adiponectin levels were determined by enzyme immunoassay (EIA). Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula.Plasma ChT activity, hs-CRP level and HOMA-IR score were significantly higher (p=0.024, p=0.002, p=0.001, respectively) while plasma adiponectin concentration was significantly lower (p=0.018) in women with PCOS compared to healthy controls. Blood ChT activity correlated positively with age, waist-to-hip ratio (WHR), BMI, hs-CRP, HOMA-IR and negatively with blood adiponectin level. After adjustment for age and BMI, ChT activity, total testosterone level and WHR remained as the independent predictors of HOMA-IR score in logistic regression analysis.ChT activity is increased in patients with PCOS in concordance with insulin resistance. These findings may reflect the pronounced risk for metabolic syndrome and atherosclerotic diseases in this particular patient group.

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