Teoman Dogru

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.

Effect of a hypocaloric diet on serum visfatin in obese non-diabetic patients

OBJECTIVE Obesity and insulin resistance are associated with classic and new cardiovascular risk factors, such as inflammatory markers and adipocytokines. The aim of this study was to examine whether weight reduction could change visfatin serum concentrations in obese patients. METHODS This was an interventional longitudinal study analyzing a population of 80 obese non-diabetic outpatients. Weight, blood pressure, fasting serum glucose, C-reactive protein, plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols, and insulin resistance (homeostatic model assessment) were measured before and after 3 mo on a hypocaloric diet. RESULTS Eighty patients were enrolled. The mean age was 46.7 +/- 16.7 y, the mean body mass index was 34.1 +/- 4.8 kg/m(2), with 20 men (25%) and 60 women (75%). After 3 mo on a hypocaloric diet, body mass index, fat mass, waist circumference, systolic blood pressure, fasting serum glucose, total cholesterol, and low-density lipoprotein cholesterol decreased. The serum concentration of visfatin decreased with weight loss (112.14 +/- 70.2 versus 99.4 +/- 58.1 ng/mL, P < 0.05). In the multivariate analysis of visfatin concentration before and after treatment, as a dependent variable, only age remained an independent predictor in the model (F = 12.5, P < 0.02), with an inverse correlation: visfatin decreased 4.1 g/mL (F = 12.5, P < 0.05) and 3.7 g/mL (95% confidence interval 1.2-6.1), respectively, for each year of age. CONCLUSION Weight reduction after a 3-mo period of a hypocaloric diet is associated with a significant decrease in circulating serum concentrations of the novel adipokine visfatin in obese subjects. Visfatin is inversely correlated with age.

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.

The relationship of serum uric acid with non-alcoholic fatty liver disease.

OBJECTIVES Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological entity which is characterized by the presence of fat droplets in hepatocytes without alcohol consumption, representing a spectrum of hepatic injuries, ranging from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. In recent years, experimental and observational studies suggest a role for serum uric acid (SUA) in NAFLD. However, there are few reports investigating SUA in histologically proven NAFLD. The aim of the present study was to evaluate the relationship of SUA with liver histology in non-diabetic patients with NAFLD. DESIGN AND METHODS A total of 242 male patients with NAFLD (102 with NASH and 140 with SS) were included. Histopathological evaluation was carried out according to Kleiners scoring scale. Hyperuricemia was diagnosed as SUA of more than 7 mg/dL. RESULTS The prevalence of hyperuricemia was 33.4%. SUA levels in patients with NASH were significantly higher than those of SS (p=0.035). Univariate and multivariate analyses both demonstrated that hyperuricemia had a significant association with younger age [OR (95%CI), 0.930 (0.884-0.979), p=0.005], higher body mass index [OR (95%CI), 1.173 (1.059-1.301), p=0.002] and hepatocellular ballooning [OR (95%CI), 1.678 (1.041-2.702), p=0.033]. CONCLUSIONS Hyperuricemia is a common finding in patients with NAFLD and is independently associated with early histological findings in this clinically relevant condition. Further longitudinal studies are needed to characterize the role of SUA in the natural history of NAFLD.

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.

Elevated Plasma Levels of Apelin in Children with Type 1 Diabetes Mellitus

ABSTRACT Background: Apelin is a novel adipocytokine produced by white adipose tissue that binds the APJ receptor with high affinity. Insulin may have a role in regulation of apelin synthesis and secretion from the adipose tissue. Objective: To investigate blood apelin concentrations in children with type 1 diabetes mellitus (T1DM) and display association of apelin with adiponectin, body mass index (BMI), lipids and insulin sensitivity. Methods: Thirty patients with T1DM and 45 healthy controls were enrolled. Apelin levels were measured along with BMI, lipids, fasting plasma glucose, HbA1c and adiponectin levels. Results: Plasma apelin and adiponectin levels were significantly higher in the diabetic group when compared to controls. No correlation was found between the apelin blood concentrations and adiponectin, BMI, lipids and insulin sensitivity. Conclusions: Children with T1DM have significantly increased circulating apelin levels when compared to healthy controls. However, no significant relation was found between the apelin and BMI, glucose, lipids and adiponectin levels, and also insulin sensitivity.