Attila Peti

Relationship of Serum Resistin Level to Traits of Metabolic Syndrome and Serum Paraoxonase 1 Activity in a Population with a Broad Range of Body Mass Index

UNLABELLED The relationship between resistin, one of the adipokines, and metabolic syndrome is not fully elucidated. Altered activity of the HDL-associated antioxidant enzyme paraoxonase 1 (PON1) that participates in the antioxidant defense mechanisms of HDL may have an important role in the obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum levels of leptin have been demonstrated. Our aim was to investigate the association of serum levels of resistin with (i) PON1 activity, and (ii) parameters of metabolic syndrome, including some that are additional for research. A total of 74 Caucasian subjects were recruited into the study and divided into 3 age and sex-matched groups. Group 1, 25 non-diabetic overweight/obese subjects with BMI of 28-39.9 kg/m (2); group 2, 25 non-diabetic obese patients with BMI >or=40 kg/m (2); and the control group 3, 24 healthy, normal-weight control subjects. Serum levels of resistin were correlated negatively with BMI (r=-0.27, P<0.05), waist circumference (r=-0.28, P<0.05), serum levels of leptin (r=-0.28, P<0.05), non-esterified fatty acids (NEFA) (r=-0.23, P<0.05), and HbA (1C) (r=-0.26, P<0.05), systolic BP (r=-0.28, P<0.05), and lipid peroxidation (measured by TBARS) (r=-0.40, P<0.01), and correlated positively with PON1 (r=0.24, P<0.05). No association was detected between the serum concentrations of resistin and the following investigated parameters: diastolic BP, levels of uric acid, glucose, insulin, or insulin resistance (measured by homeostasis model assessment, HOMA-IR), triglyceride, total cholesterol, LDL-C, and HDL-C. During multiple regression analyses BMI and TBARS were independent predictors of PON1, while age, gender, blood pressure, HOMA-IR, LDL-C, HDL-C, and resistin were not. CONCLUSIONS Among the study subjects, serum levels of resistin showed a positive, although not independent correlation with serum PON1, and a negative correlation with numerous parameters of the metabolic syndrome (i.e. adiposity, blood pressure, levels of leptin, free fatty acid, glycosylated hemoglobin, and lipid peroxidation). BMI and TBARS are independent predictors of PON1 activity.

Relationship of adipokines and non-esterified fatty acid to the insulin resistance in non-diabetic individuals

Background: Altered secretion of adipokines and non-esterified fatty acid (NEFA) seems to play a pivotal role in the abdominal obesity-related insulin resistance (IR). Aim: To determine semi-quantitatively the impact of serum NEFA, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), leptin, adiponectin, and resistin levels on IR measured by homeostasis model assessment (HOMA-IR). Material/subjects: Seventy-four Caucasian subjects forming 3 age-, and sex-matched groups were included into the study [Group 1 and 2: non-diabetic obese patients, no.= 25, body mass index (BMI): 28–39.9 kg/m2, no.=25, BMI≥40 kg/m2, respectively, and Group 3: 24 healthy, normal weight control subjects]. Methods: Serum levels of NEFA and adipokines as well as other metabolic variables including HOMA-IR were measured. Results: HOMA-IR was associated positively with BMI, waist circumference, serum NEFA, leptin, IL-6, and TNF-α levels, negatively with adiponectin, with no significant relation to resistin. In multiple regression analyses, of these factors leptin was a strong, IL-6 and adiponectin were weak independent predictors of HOMA-IR, while the others were not significant determinants of HOMA-IR. However, even together, they explained only 35–36% of variance of HOMA-IR. Conclusions: Although IR has associations with many of the investigated parameters, of these, only serum level of leptin, and in lesser degree IL-6 and adiponectin are independent determinants of the severity of IR. Moreover, even together they explain only a minority of variance IR.

Associations of Adiponectin with Paraoxonase 1 and sE-Selectin in Hemodialyzed Patients

Background/Aims: In hemodialyzed (HD) patients, adiponectin and sE-selectin levels are elevated, while antioxidant paraoxonase 1 activity (PON1) is decreased. We determined if the hyperadiponectinemia in HD patients has a protective effect on the decrease in PON1 and elevation in sE-selectin in kidney failure. Methods and Design: Predialysis serum adiponectin, PON1 and sE-selectin as well as other metabolic variables were measured in 70 HD patients. Results: Adiponectin had (1) no association with PON1 or sE-selectin, (2) a positive association with dialysis efficiency and HDL-C, and (3) an inverse association with BMI, waist circumference, HOMA IR, triglyceride, hsCRP, fibrinogen, and albumin. Moreover, albumin, BMI, and HOMA-IR were independent negative predictors of adiponectin. Conclusions: In kidney failure, in contrast to normal renal function, higher adiponectin levels had no correlation with PON1 activity or the sE-selectin level. However, adiponectin has an association with dialysis efficiency and, similar to individuals with preserved kidney function, traits of metabolic syndrome. In addition to BMI and HOMA-IR, the serum albumin concentration is also one of the independent negative predictors of the serum adiponectin level. Collectively, these findings may add details to the understanding of the role that adiponectin plays in chronic renal disease related to ‘reverse epidemiology’.

Serum and follicular fluid fetuin-A in women undergoing in vitro fertilization.

Abstract Backgrounds: This case-control study was designed to assess the possible role of fetuin-A, a multifunctional protein, in reproductive processes of women undergoing in vitro fertilization (IVF). Methods: Paired serum and follicular fluid (FF) samples were obtained from 35 unselected patients who received IVF treatment. Their main clinical chartacteristics: age 35.2±5.4 years, BMI 22.9±2.8, duration of infertility 3.2±2.0 years, gonadotropin administered 1199.4±202.3 IU, and estradiol level on day 6 of stimulation 1827±1342 pmol/L. In total 25 healthy women of similar age admitted for minor elective surgery served as controls for serum analysis. Fetuin-A and high-sensitivity C-reactive protein (hsCRP) were measured in serum and FF by using commercially available ELISA kits and turbidimetric immunoassay, respectively. Results: Serum fetuin-A levels of patients participating IVF are markedly elevated when compared to those of healthy women (1.30±0.58 g/L vs. 0.55±0.09 g/L, p<0.000). Fetuin-A in FF proved to be comparable to its serum levels (1.17±0.45 g/L) and no relationship could be detected between the respective individual values. Moreover, markers of reproductive potential (number of oocytes and embryos) appeared to be independent of serum and FF fetuin-A. hsCRP in serum and FF was not related to fetuin-A and did not influence the number of oocytes and embryos. Conclusions: Fetuin-A concentration is high in FF of patients undergoing IVF, however, it can not be used as an estimate of fertilization success.

The Impact of Osteocalcin, Osteoprotegerin and Osteopontin on Arterial Stiffness in Chronic Renal Failure Patients on Hemodialysis

Background/Aims: This cross-sectional study was designed to assess the relationship between vascular stiffness (VS) and bone-related proteins involved in the development of arteriosclerosis in patients on regular hemodialysis (HD). Methods: 68 consecutive patients in stable clinical condition who received regular HD in the FMC Dialysis Center, Pécs were included. VS parameters (carotid-femoral pulse wave velocity – PWV, aortic augmentation index - AIx) were determined by applanation tonometry (SphygmoCor, AtCor Medical, Sidney) and the routine latoratory test were completed with measurements of osteocalcin (OC), osteopontin (OP) and osteoprotegerin (OPG) by using commercially available ELISA kits. 35 heathcare workers served as controls. Results: In patients on regular HD PWV markedly increased and there was several-fold elevation in the interrelated bone-specific proteins (OC, OP, OPG). PWV was found to be independently associated only with OC (β:-0.25, p<0.029) and age (r=0.411,p<0.000), but risk factors for arterial calcification had significant impact on OC (systolic blood pressure, hsCRP, BMI), OPG (age, BMI) and OP (LDL-cholesterol). Conclusion: Except for OC, our results failed to document direct association of vascular lesion with OP and OPG, therefore their high circulating levels may be an epiphenomenon or they may have counter-regulatory role to attenuate the uremic calcification process.

PS 05-63 PRO- AND ANTI-INFLAMMATORY FACTORS AND VASCULAR STIFFNESS IN END-STAGE RENAL DISEASE PATIENTS

Objective: Vascular calcification (VC) has crucial importance in the accelerated arteriosclerosis of chronic renal disease patients. The aim of this study was to assess the extent of arteriosclerotic lesions and to relate vascular stiffness parameters to pro-inflammatory markers (hsCRP, TNF-&agr;, TGF-&bgr;1) and to protective factors (&agr;-Klotho, fetuin-A, vitamin D3) in patients on chronic hemodialysis. Design and Method: 96 consecutive patients in stable condition were enrolled. 20 healthy individuals served as controls. Beside routine biochemical parameters, TNF-&agr;, TGF-&bgr;1 &agr;-Klotho and fetuin-A were measured with ELISA. Carotid-femoral pulse wave velocity was measured using applanation tonometry (SphygmoCor, AtCor Medical Australia) before hemodialysis sessions. Carotid-femoral pulse wave velocity (cfPWV) was calculated. Results: Pro-inflammatory (pro-calcigenic) biomarkers (hsCRP, TNF-&agr;, TGF-&bgr;1) were elevated (p < 0.01), whereas anti-inflammatory (anti-atherosclerotic) factors (fetuin-A: p < 0.05, &agr;-Klotho: p < 0.01, vitamin D3 p < 0.01) depressed compared to controls. cfPWV correlated positively with total cholesterol (r = 0.244, p < 0.05) and fetuin-A (r = 0.282, p < 0.05) but inversely with the time spent on dialysis (r = -0.262, p < 0.05). hsCRP was negatively influenced by plasma vitamin D3 (&bgr; = −0.23, p < 0.01), sodium (&bgr; = −0.26, p < 0.00) and albumin levels (&bgr; = −0.36, p < 0.00), positively by BMI (&bgr; = 0.76, p < 0.00). TNF&agr; and TGF&bgr;1 as dependent variables were found to correlate with &agr;-Klotho (&bgr; = 0.41, p < 0.00) and plasma creatinine (&bgr; = 0.30, p < 0.003), as well as with fetuin-A (&bgr; = −0.24, p < 0.02) and plasma albumin (&bgr; = 0.33, p < 0.002), Fetuin-A showed significant negative correlation with age (&bgr; = −0.225, p < 0.05), TGF-&bgr;1 (&bgr; = −0.228, p < 0.02), and dialysis time (&bgr; = −0.26, p < 0.01), while positive relationship was found between fetuin-A and triglyceride levels (&bgr; = 0.43, p < 0.00). &agr;-Klotho correlated positively with TNF-&agr; (&bgr; = 0.44, p < 0.00) and negatively with plasma calcium (&bgr; = −0.24, p < 0.01). Conclusions: Our study confirmed that the pro-inflammatory cascade of arteriosclerosis was activated and inflammatory biomarkers (hsCRP, TNF-&agr;, TGF-&bgr;1) prevailed over protective factors (vitamin D, &agr;-Klotho, Fetuin-A) in patients on hemodialysis. We demonstrated that PWV was significantly affected by total cholesterol, fetuin-A and dialysis time. Several clinical and laboratory factors were associated with pro- and anti-inflammatory biomarkers rather than PWV.