Serkan Tapan

Plasma Apelin and ADMA Levels in Patients with Essential Hypertension

Both apelin and asymetric dymethyl arginine (ADMA) regulate blood pressures. Low apelin and high ADMA levels have been reported in several cardiometabolic disorders. However, there is no data about ADMA and apelin levels in essential hypertension and any relationship between them. We investigated a group of newly diagnosed and untreated 30 young hypertensive men and 30 healthy controls. Apelin levels were significantly lower and the ADMA levels were significantly higher in the patients (p = 0.04 for both). Both ADMA and apelin were related to the systolic blood pressures (SBP) (beta = −0.393, p = 0.003; beta = 0.285, p = 0.03, respectively). Future studies are necessary in order to clearly define the role of ADMA and apelin in the pathogenesis of essential hypertension.

Plasma fetuin-A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome (MetS) is closely associated with an increased risk of cardiovascular disease. Fetuin‐A is associated with MetS and NAFLD. We investigated the relationship of circulating fetuin‐A level with markers of endothelial dysfunction and presence of carotid atherosclerosis in subjects with NAFLD.

LDL-cholesterol lowering increases plasma apelin in isolated hypercholesterolemia

Apelin, a relatively newer adipokine with various actions in cardiovascular system, was recently reported to decrease in dyslipidemia. The present study addresses whether plasma apelin increases after hypolipidemic intervention either through therapeutic life style change (TLC) or statin treatment. A total of 134 patients were subjected to treatment with a TLC intervention for 12 weeks. Of these, 116 successfully completed the period, and LDL-cholesterol level decreased to target level (<160 mg/dL) in 54 (46.5%) individuals. The remaining 62 patients were treated with rosuvastatin for 12 weeks, and 56 of them finished the study. Circulating apelin, adiponectin, leptin, TNF-alpha, hsCRP and insulin levels were determined both at baseline and after TLC intervention and statin treatment. There was no significant change in plasma apelin concentration in patients unresponsive to TLC (p=0.110). LDL-cholesterol lowering either through TLC or statin treatment was accompanied by an increase in plasma apelin (p=0.000, p=0.020) and adiponectin (p=0.001, p=0.011). Serum leptin decreased after successful TLC (p=0.042/male, p=0.023/female) but not after statin treatment (p=0.959/male, p=0.134/female). Serum TNF-alpha (p=0.902) and plasma hsCRP (p=0.135) levels remained unchanged after TLC intervention but decreased after statin treatment (p=0.000, p=0.023, respectively). Plasma insulin and homeostasis model assessment scores decreased after TLC (p=0.000 for both) but not rosuvastatin treatment (p=0.865, p=0.722, respectively). In conclusion, independent of the type of treatment, reduction in LDL-cholesterol levels in otherwise healthy people with isolated dyslipidemia results in an increase in plasma apelin concentration. More experiments may show a substantial role for this peptide in the mechanism of atherosclerosis.

Mean platelet volume and its relationship with carotid atherosclerosis in subjects with non-alcoholic fatty liver disease.

Abstract Background. Non-alcoholic fatty liver disease (NAFLD) is linked to an increased risk of cardiovascular disease. Mean platelet volume (MPV), a determinant of platelet activation, is an emerging risk factor for atherothrombosis. Aims. The aim of this study was to investigate the levels of MPV in subjects with NAFLD having no confounding factors for atherosclerosis such as obesity, diabetes mellitus, and hypertension. In addition, the possible relationship between MPV and carotid artery intima media thickness (CIMT), a well known marker of subclinical atherosclerosis, was also studied. Methods. MPV and CIMT levels were measured in 60 biopsy-proven NAFLD subjects and 54 healthy controls. Age and sex were similar between two groups. Results. Body mass index and waist circumference levels were higher in the NAFLD group when compared to the controls. There were no differences between the two groups regarding LDL cholesterol levels, whereas HDL cholesterol levels were lower in the NAFLD group. MPV and CIMT levels were not different between the two groups. According to the correlation analyses, CIMT levels were positively correlated to age in patients with NAFLD. However, no significant correlation was found between MPV and CIMT levels. Conclusions. The results of this study do not show any difference in MPV levels between subjects with NAFLD and controls. These finding suggests that in the absence of other metabolic risk factors, MPV might not be involved in the mechanism(s) of increased cardiovascular risk in NAFLD.

Decreased small dense LDL levels in Gilbert's syndrome.

OBJECTIVE To investigate the role of small dense low density lipoprotein cholesterol (sd-LDL-C) in the mechanism of decreased incidence of cardiovascular disease in Gilberts syndrome (GS). DESIGN AND METHODS sd-LDL-C, ox-LDL, and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS (n=42) and compared to healthy controls (n=52). RESULTS Age, gender and body mass index (BMI) distributions were similar between the two groups. sd-LDL-C, ox-LDL and hs-CRP levels were lower in GS than the healthy controls (p<0.001, p<0.001 and p=0.001, respectively). Unconjugated bilirubin was negatively correlated with sd-LDL-C, ox-LDL and hs-CRP (r=-0.594, p<0.001; r=-0.249, p=0.016 and r=-0.373, p<0.001 respectively). In addition, sd-LDL-C was positively correlated with ox-LDL (r=0.307, p=0.003). CONCLUSIONS The findings of this preliminary study suggest that reduced sd-LDL-C, ox-LDL and hs-CRP levels may have a role in preventing atherosclerosis in subjects with GS.

Metformin and oral contraceptive treatments reduced circulating asymmetric dimethylarginine (ADMA) levels in patients with polycystic ovary syndrome (PCOS)

There is a little information in literature about circulating asymmetric dimethylarginine (ADMA) concentrations in polycystic ovary syndrome (PCOS) and the results reported are discrepant. In this study, therefore, we aimed (1) to determine the circulating ADMA concentrations in 44 women with PCOS and 22 age- and BMI-matched healthy controls, (2) to evaluate its correlations with insulin resistance, gonadotrophins, and androgen secretion, and (3) to compare effects of metformin and ethinyl estradiol-cyproterone acetate (EE/CPA) treatments on circulating ADMA concentrations. In conclusion, our data indicate that circulating ADMA concentrations in non-obese, non-hypertensive and young women with PCOS are significantly higher than healthy controls and they improved by a 3-month course of metformin and oral contraceptive treatments.

The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus

AIMS Circulating visfatin levels are altered in insulin resistant states. We evaluated the effects of two insulin-sensitizing hypoglycemic agents on plasma visfatin and adiponectin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM). METHODS Forty-four patients with T2DM were randomized to treatment either with pioglitazone (15-45mg/day) or metformin (1000-2000mg/day). Plasma visfatin and adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) scores were determined at baseline and at 12th week of treatment. RESULTS By the end of the 12th week, fasting plasma glucose, HbA1c, HOMA-IR scores and waist circumferences improved equally in both treatment arms. HDL cholesterol and adiponectin levels increased only in the pioglitazone group (p=0.01 and p=0.003, respectively). On the other hand, metformin treatment had additional regulatory effects on BMI, blood pressure and total and LDL-cholesterol levels (p=0.002, p=0.01, p=0.004, p=0.001 and p<0.001, respectively). Neither pioglitazone nor metformin displayed a significant effect on circulating visfatin concentration. CONCLUSIONS Despite improvements in insulin sensitivity and glycemic regulation, either pioglitazone or metformin treatment did not result in any effect on blood visfatin levels in patients with treatment naïve T2DM.

Soluble CD40 ligand and soluble P-selectin levels in Gilbert's syndrome: A link to protection against atherosclerosis?

OBJECTIVE To investigate the role of CD40 ligand and P-selectin in the mechanism of decreased incidence of cardiovascular disease in Gilberts syndrome (GS). DESIGN AND METHODS The soluble forms of CD40 ligand (sCD40L) and P-selectin (sP-selectin), and high sensitive C reactive protein (hs-CRP) levels were investigated in subjects with GS (n=25) and compared to healthy controls (n=53). RESULTS sCD40L and hs-CRP levels were significantly lower in GS compared to the controls (0.33+/-0.27 vs 0.71+/-0.37 ng/mL, p<0.001 and 0.51+/-0.45 vs 1.16+/-1.31 mg/L, p=0.046, respectively). Both sCD40L and hs-CRP were negatively correlated with total bilirubin (r=-0.5, p<0.001 and r=-0.34, p=0.002, respectively). sP-selectin levels were lower in GS when compared to the controls but the difference did not reach statistical significance (p=0.052). No correlation was found between the plasma levels of sCD40L, sP-selectin and hs-CRP. CONCLUSION These novel findings suggest that reduced sCD40L and hs-CRP concentrations may have a role in the mechanism of protection against atherosclerosis in GS.

Comparison of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels using mass spectrometer and urine albumin creatinine ratio as a predictor of development of diabetic nephropathy.

Abstract Background. Measurement of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) has recently become more popular as a means of assessing oxidative stress in the human body. The aim of this study is to compare the levels of urine 8-OHdG in patients with type 2 diabetes with and without nephropathy and to evaluate its role as a biochemical marker for distinguishing these patients from healthy and patients without complications. Methods. For this purpose, 52 patients with type 2 diabetes mellitus (32 with nephropathy (DMN), 20 without nephropathy (DM)) and 20 healthy control subjects (C) were included in this study. The urine concentrations of 8-OHdG were measured by modified LC-MS/MS method and compared with the first morning voiding urine albumin/creatinine ratio (UACR) and HbA1c values of the same patients. Results. The concentrations of urine 8-OHdG in DMN and DM patients were higher than those of the control subjects (3.47 ± 0.94, 2.92 ± 1.73, 2.1 ± 0.93 nmol/mol creatinine, respectively). But there was no statistical difference between DMN and DM (p = 0.115). There is significant correlation between urinary 8-OHdG and UACR (r = 0.501, p < 0.001). According to ROC analysis, the AUC value of HbA1c was higher than the value of the AUC of 8-OHdG (0.882 and 0.771, respectively). Conclusions. This study shows that the urine 8-OHdG levels increase in diabetic patients. However, urinary 8-OHdG is not a useful clinical marker, compared with UACR, to predict the development of diabetic nephropathy in diabetic patients.

Comparison of plasma and erythrocyte membrane fatty acid compositions in patients with end-stage renal disease and type 2 diabetes mellitus

BACKGROUND In this study, we aimed to compare the serum lipid profile and fatty acid (FA) compositions of erythrocyte membrane (EM) and plasma in three different patient groups (group 1: type 2 diabetes mellitus (T2DM)+end-stage renal disease (ESRD), group 2: ESRD, group 4: T2DM) and healthy controls (group 3) simultaneously. METHODS 40 ESRD patients treated with hemodialysis (HD) in Gulhane School of Medicine (20 with T2DM) and 32 controls (17 with T2DM, 15 healthy controls) were included in the study. Plasma and EM FA concentrations were measured by gas chromatography-flame ionization detector (GC-FID). RESULTS Plasma and EM palmitic acid (PA) and stearic acid (SA) levels were significantly higher in T2DM patients compared to controls (p=0.040 and p=0.002 for plasma, p=0.001 and p=0.010 for EM, respectively). EM docosahexaenoic acid (DHA) levels were also significantly lower in patients with ESRD+T2DM and ESRD compared to controls (p=0.004 and p=0.037, respectively). CONCLUSIONS Patients with insulin resistance display a pattern of high long chain saturated FAs (PA, SA and arachidic acids). However, while there are no recognized standards for normal EM DHA content, decreased levels of EM DHA in ESRD patient groups (groups 1 and 2) suggest that there may be reduced endogenous synthesis of DHA in HD subjects, due to the decreased functionality of desaturase and elongase enzymes. Because membrane PUFA content affects membrane fluidity and cell signaling, these findings are worthy of further investigation.