Ocena stężeń FGF-21 — nowej adipocytokiny w cukrzycy typu 2

Introduction: Fibroblast growth factor 21 FGF-21 is a newly discovered adipocytokine which may play a vital role in improvement of insulin sensitivity and pathogenesis of type 2 diabetes. The aim of the study was to assess FGF-21 concentrations in the serum of patients with type 2 diabetes, in comparison to a control group, and evaluate the possible relationships between the studied cytokine and selected clinical and biochemical parameters Material and methods: The study was conducted in 64 patients with type 2 diabetes, 28 women and 36 men aged 47-70 (median age 61.5), with a median duration of diabetes of 8.5 years. In fasting serum samples, concentrations of glucose, insulin, lipids profile parameters, creatinine, C-reactive protein (CRP), fibrinogen, HbA1c, adiponectin, and FGF-21 were determined. The control group comprised 20 healthy persons matched for age to the study group, with no disturbances in carbohydrate metabolism: 14 women and 8 men. Results: We found significant differences concerning the medians of body mass index (BMI) 32.4 kg/m2 v. 24.1 kg/m2, p < 0.001; waist circumference 114 cm v. 81 cm, p < 0.001; HDL cholesterol 42.5 mg/dl v. 62.5 mg/dl, p < 0.001; triglyceride (TG) 152 mg/dl v. 99 mg/dl, p < 0.01 in the studied group, in comparison with the control group, respectively. In patients with diabetes, median FGF-21 concentration was 239.9 pg/ml and was significantly greater in comparison to the control group: 112.6 pg/ml p < 0.01. Median adiponectin concentration in patients with type 2 diabetes was significantly lower in comparison to the control group, 7.5 ng/ml v. 9.95 ng/ml, p < 0.05. Significant correlations between FGF-21 concentrations and adiponectin (r = -0.24, p < 0.05), weight (r = 0.27, p < 0.05), glucose (r = 0.27, p < 0.05), HDL cholesterol (r = -0.26, p < 0.05), TG (r = 0.27, p < 005), and estimated glomerular filtration rate (eGFR) (r = -0.28, p < 0.05) were observed. No significant correlations between FGF-21 and parameters of metabolic control, markers of inflammatory status, and insulin resistance, or the presence of vascular complications of diabetes, were noticed. Conclusions: On the basis of the conducted studies it can be concluded that the greater FGF-21 concentration observed in the examined group of patients with type 2 diabetes may result from a compensatory reaction to metabolic disturbances or tissue resistance to this cytokine. The negative correlation between FGF-21 and eGFR suggests renal elimination of the examined compound. (Pol J Endocrinol 2010; 61 (1): 50-54)Wstęp: Czynnik wzrostu fibrolastów 21 (FGF-21, fibroblast growth factor 21) jest stosunkowo niedawno odkrytą adipokiną, mogącą odgrywać istotną rolę w poprawie insulinowrażliwości i patogenezie cukrzycy tytu 2. Celem pracy była ocena stężenia FGF-21 w surowicy krwi pacjentów cukrzycą typu 2 w porównaniu z grupą kontrolną, oraz znalezienie zależności pomiędzy tą cytokiną a innymi parametrami klinicznymi i biochemicznymi. Materiał i metody: Badania wykonano u 64 pacjentów z cukrzycą typu 2, w tym 28 kobiet i 36 mężczyzn w wieku 47-70 lat (średnia wieku 61,5), z medianą czasu trwania choroby 8,5 roku. W próbkach krwi pobranej na czczo wykonywano oznaczenia stężeń glukozy, insuliny, białka C-reaktywnego (CRP, C-reactive protein), fibrynogenu, lipidogramu, kreatyniny, HbA1c, adiponektyny i FGF-21. Grupę kontrolną stanowiło 20 osób (14 kobiet i 8 mężczyzn) z medianą wieku 58 lat, bez zaburzeń gospodarki węglowodanowej. Wyniki: W grupie badanej stwierdzono, w porównaniu z grupą kontrolną, istotne różnice w zakresie median wskaźnika masy ciała (BMI, body mass index) 32,4 kg/m2 v. 24,1 kg/m2, p < 0,001; obwodu talii 114 cm v. 81 cm, p < 0,001; cholesterolu frakcji HDL 42,5 mg/dl v. 62,5 mg/dl, p < 0,001; triglicerydów (TG, triglyceride) 152 mg/dl v. 99 mg/dl, p < 0,01. U pacjentów z cukrzycą mediana stężenia FGF-21 wynosiła 239,8 pg/ml i była istotnie wyższa w porównaniu z grupą kontrolną: 112,6 pg/ml, p < 0,001. Mediana stężenia adiponektyny u pacjentów z cukrzycą była istotnie niższa w porównaniu z grupą kontrolną, 7,5 ng/ml v. 9,95 ng/ml, p < 0,01. Zaobserwowano istotne zależności pomiędzy stężeniami FGF-21 a adiponektyną (r = -0,24, p < 0,05), masą ciała (r = 0,27, p < 0,05), glukozą (r = 0,27, p < 0,05), cholesterolem frakcji HDL (r = -0,26, p < 0,05), TG (r = 0,27, p < 005) oraz wielkością przesączania kłębuszkowego (eGFR, estimated glomerular filtration rate) (r = -0,28, p < 0,05). Nie znaleziono istotnych zależności pomiędzy stężeniem FGF-21 a parametrami wyrównania metabolicznego, wykładnikami stanu zapalnego i insulinooporności, jak również obecnością powikłań naczyniowych choroby. Wnioski: Na podstawie przeprowadzonych badań można przypuszczać, że obserwowane wyższe stężenia FGF-21 w badanej grupie pacjentów z cukrzycą typu 2, mogą wynikać z kompensacyjnej reakcji na zaburzenia metaboliczne bądź też są wynikiem tkankowej oporności na tę cytokinę. Ujemna korelacja stężeń FGF-21 z eGFR sugeruje eliminację drogą nerkową badanego związku. (Endokrynol Pol 2010; 61 (1): 50-54

Analysis of serum homocysteine in the laboratory practice - comparison of the direct chemiluminescence immunoassay and high performance liquid chromatography coupled with fluorescent detection

Introduction: Effective diagnosis of cardiovascular diseases requires the right tools to be used enabling selective and sensitive analysis of their biomarkers. One of them is homocysteine (Hcy), nowadays determined by immunoassays and chromatographic methods. This study aims to compare the results obtained by direct chemiluminescence immunoassay (CLIA) and high performance liquid chromatography with fluorescent detection (HPLC-FD) using commercial kits. Materials and methods: Homocysteine concentration was determined in serum samples obtained from 101 individuals, using Atellica IM HCY (Siemens Healthineers, Erlangen, Germany) and HCY in plasma/serum – HPLC-FD (Chromsystems Instruments & Chemicals GmbH, Gräfelfing, Germany) tests validated for routine analysis. The latter was applied as a reference method. The comparability and agreement between the tested methods were evaluated using the Passing-Bablok (PB) regression analysis and the Bland-Altman (BA) method of the differences analysis. Results: Studies showed that CLIA gives higher Hcy concentrations (15.7 ± 4.14 μmol/L). Passing-Bablok regression analysis of the results obtained with CLIA (y) compared with HPLC-FD (x) yielded an intercept of 0.22 (95%CI: - 2.16 to 2.46) and slope of 1.58 (95%CI: 1.33 to 1.87). Bland-Altman analysis demonstrated a systematic positive bias for CLIA of 5.85 ± 2.77 μmol/L. Conclusions: Methods disagreement precludes their interchangeability. Lower Hcy values by HPLC-FD result from its greater selectivity. High performance liquid chromatography with fluorescent detection should be considered as preferential method for analysing Hcy in blood serum as well as the recommended reference method for routine clinical analysis. This fact, however, imposes the need to establish new reference ranges

Myeloperoxidase level and inflammatory markers and lipid and lipoprotein parameters in stable coronary artery disease

Abstract Background Myeloperoxidase (MPO) impairing endothelial functions. We investigated whether increasing concentration of myeloperoxidase (MPO) and inflammatory markers induce progression and incident acute coronary syndrome (ACS) in stable coronary artery disease (SCAD) patients. Therefore, the concentration of MPO, lipids, lipoproteins (apo(apolipoprotein) AI, apoB, lipoprotein associated phospholipase A2 (LpPLA2) level), inflammatory markers (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) concentration) were examined. Methods This study concerned 67 SCAD patients divided into groups: all patients, patients with MPO  300 ng/ml concentration and 15 controls. ApoAI, apoB and hsCRP levels were examined using the immunonephelometric method, and MPO, LpPLA2, IL-6, TNF-α concentration was performed by using Quantikine ELISA kit R&D Systems. Results In the all patients, and in group with MPO 200–300 ng/ml TC, LDL-C, nonHDL-C, LpPLA2 concentration and TC/HDL-C, LDL-C/HDL-C ratios were insignificant, and significantly higher concentration of TG, apoB, MPO, inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios but HDL-C, apoAI level and HDL-C/apoAI ratio were significantly reduced. In the group of patients with MPO  300 ng/ml concentration of TC, LDL-C, nonHDL-C, apoAII, LpPLA2 and LDL-C/HDL-C ratios were not significant, but HDL-C and apoAI concentrations were significantly decreased. The concentrations of TG, apoB, MPO and inflammatory markers and TG/HDL-C, MPO/apoAI, MPO/HDL-C ratios were significantly increased compared to the controls. The apoAI concentration was significantly decreased and the concentration of MPO and hsCRP as well as MPO/apoAI and MPO/HDL-C ratios were significantly higher as compared to the group of patients with MPO  300 ng/ml showed a positive correlation between the concentration of MPO and the level of hsCRP and IL-6, and a negative correlation between MPO/apoAI ratio and the concentration of HDL-C, apoAI and apoAII. Conclusion The results suggest that moderate dyslipidemia and dyslipoproteinemia deepening of inflammation, and inflammation slowly induce increase MPO concentration which decrease apoAI and HDL-C level and disturb HDLs function. The increasing MPO level and MPO/HDL-C, MPO/apoAI ratios can differentiate the SCAD patients at the risk of acute coronary syndrome (ACAD) and stroke

γ-amino butyric acid (GABA) level as an overall survival risk factor in breast cancer

Introduction The γ-amino butyric acid (GABA) plays important role in the proliferation and migration of cancer cells. The aim of the study was to evaluate the level of GABA in breast cancer, in relation to clinical and epidemiological data. Material and Methods The study was conducted on 89 patients with breast cancer in stage I-II. GABA level was assessed using spectrofluorometric method in tumour homogenates. Immunoexpression of E-cadherin was evaluated histologically on paraffin fixed specimens. Overall and disease-free survival was assessed for a 15-year interval period. Results Median overall survival was significantly longer (127.2 months) in patients with a high level of GABA (>89.3 μg/1), compared with a group with a low level of the amino acid (106.4 months). Disease-free survival was insignificantly different – 99 and 109 months, respectively. A significantly longer overall survival (131.2 months) was seen among patients with a high level of GABA and positive E-cadherin immunoexpression, compared with a group characterized by a low level of GABA and lack of E-cadherin immunorectivity (98.1 months). The co-existence of negative immunoexpression of E-cadherin and low GABA concentration resulted in a six-fold increase in the risk of death (HR=6.03). Conclusions GABA has a significant prognostic value in breast cancer. Co-existence of a low level of GABA and loss of E-cadherin immune-expression seems to be a new, independent, and negative prognostic marker of the neoplasm

γ-amino butyric acid (GABA) level as an overall survival risk factor in breast cancer

Introduction The γ-amino butyric acid (GABA) plays important role in the proliferation and migration of cancer cells. The aim of the study was to evaluate the level of GABA in breast cancer, in relation to clinical and epidemiological data. Material and Methods The study was conducted on 89 patients with breast cancer in stage I-II. GABA level was assessed using spectrofluorometric method in tumour homogenates. Immunoexpression of E-cadherin was evaluated histologically on paraffin fixed specimens. Overall and disease-free survival was assessed for a 15-year interval period. Results Median overall survival was significantly longer (127.2 months) in patients with a high level of GABA (>89.3 μg/1), compared with a group with a low level of the amino acid (106.4 months). Disease-free survival was insignificantly different – 99 and 109 months, respectively. A significantly longer overall survival (131.2 months) was seen among patients with a high level of GABA and positive E-cadherin immunoexpression, compared with a group characterized by a low level of GABA and lack of E-cadherin immunorectivity (98.1 months). The co-existence of negative immunoexpression of E-cadherin and low GABA concentration resulted in a six-fold increase in the risk of death (HR=6.03). Conclusions GABA has a significant prognostic value in breast cancer. Co-existence of a low level of GABA and loss of E-cadherin immune-expression seems to be a new, independent, and negative prognostic marker of the neoplasm

Levels of renalase and advanced oxidation protein products with regard to catecholamines in haemodialysed patients

Introduction The main mediators of the sympathetic nervous system in the effectors part are catecholamines (CA). An increased sympathetic nerve activity observed in chronic kidney disease (CKD), is due to a raised level of CA in plasma. Renalase is a protein secreted by the kidneys, composed of 342 amino acids, which is able to metabolize the circulating CA and possibly play an important role in the regulation of sympathetic tone and blood pressure. Also, oxidative stress, defined as a disruption of the equilibrium between the generation of oxidants, is a crucial factor in the development of the inflammatory syndrome associated with CKD. The advanced oxidation protein products (AOPP) represent exquisite markers of phagocyte-derived oxidative stress. Objective The aim of the study was to investigate the concentration of renalase and explore the associations between AOPP with regards to CA in haemodialysis (HD) patients. Material and Methods The study was conducted among 50 residents of the municipality and neighbouring villages in the province of Lublin, central-eastern Poland. Results In the studied patients, it was found that an average concentration of renalase was 44.8 ± 6.5 μg/mL, whereas of AOPP plasma levels – 57.5 ± 21.5 μmol/L. The results demonstrated the correlation between levels of renalase and AOPP in the HD patients. Indeed, elevated levels of renalase and AOPP in HD may be due to the presence of uremic toxins in blood. The concentration of urea affects the plasma concentrations of AOPP and renalase causing a direct relationship between renalase and AOPP. However, there is no clear relationship between renalase and circulating catecholamines in HD patient

Can chronic heart failure induce kidney function damage?

Accelerated atherosclerosis and increased cardiovascular events have been extensively documented in patients with end stage chronic kidney disease

Levels of renalase and advanced oxidation protein products with regard to catecholamines in haemodialysed patients

Introduction The main mediators of the sympathetic nervous system in the effectors part are catecholamines (CA). An increased sympathetic nerve activity observed in chronic kidney disease (CKD), is due to a raised level of CA in plasma. Renalase is a protein secreted by the kidneys, composed of 342 amino acids, which is able to metabolize the circulating CA and possibly play an important role in the regulation of sympathetic tone and blood pressure. Also, oxidative stress, defined as a disruption of the equilibrium between the generation of oxidants, is a crucial factor in the development of the inflammatory syndrome associated with CKD. The advanced oxidation protein products (AOPP) represent exquisite markers of phagocyte-derived oxidative stress. Objective The aim of the study was to investigate the concentration of renalase and explore the associations between AOPP with regards to CA in haemodialysis (HD) patients. Material and Methods The study was conducted among 50 residents of the municipality and neighbouring villages in the province of Lublin, central-eastern Poland. Results In the studied patients, it was found that an average concentration of renalase was 44.8 ± 6.5 μg/mL, whereas of AOPP plasma levels – 57.5 ± 21.5 μmol/L. The results demonstrated the correlation between levels of renalase and AOPP in the HD patients. Indeed, elevated levels of renalase and AOPP in HD may be due to the presence of uremic toxins in blood. The concentration of urea affects the plasma concentrations of AOPP and renalase causing a direct relationship between renalase and AOPP. However, there is no clear relationship between renalase and circulating catecholamines in HD patient

Polycystic ovary syndrome: clinical implication in perimenopause

Polycystic ovary syndrome (PCOS), a hyperandrogenic disorder, is the commonest endocrinopathy in premenopausal women. This syndrome is associated with fertility problems, clinical manifestations of hyperandrogenism and metabolic disturbances, particularly insulin resistance and obesity. There is a great body of evidence that patients with PCOS present multiple cardiovascular risk factors and cluster components of metabolic syndrome from early ages. The presence of comorbidities such as abdominal obesity, insulin resistance, type 2 diabetes, hypertension places these females at an increased risk of future cardiovascular events. However, the extent to which PCOS components are present in perimenopausal women and the degree to which PCOS increases various risk factors in addition to the known risk of the perimenopausal period have not been fully determined. The perimenopausal period per se is associated with weight gain and an increased cardiovascular risk, which may be additionally aggravated by the presence of metabolic disturbances connected with PCOS. The phenotype of PCOS may improve with aging and it is still uncertain whether the presence of PCOS significantly increases the cardiovascular risk later in women’s life. Most recent data suggest that the prevalence of cardiovascular diseases and the related long-term consequences in females with PCOS seem to be lower than expected. This manuscript reviews long-term consequences of PCOS and considers their clinical implications in perimenopause

Relationship between microRNA-146a expression and plasma renalase levels in hemodialyzed patients.

microRNA (miRNA) belongs to the non-coding RNAs family responsible for the regulation of gene expression. Renalase is a protein composed of 342 amino acids, secreted by the kidneys and possibly plays an important role in the regulation of sympathetic tone and blood pressure. The aim of the present study was to investigate plasma renalase concentration, and explore the relationship between miRNA-146a-5p expression and plasma renalase levels in hemodialyzed patients.The study population comprised 55 subjects who succumbed to various cardiac events, 27 women and 28 men, aged 65-70 years. The total RNA including miRNA fraction was isolated using QiagenmiRNEasy Serum/Plasma kit according to the manufacturer's protocol. The isolated miRNAs were analyzed using a quantitative polymerase chain reaction (qRT-PCR) technique. The plasma renalase levels were measured using a commercial ELISA kit.In the group of patients with high levels of renalase, higher miRNA-146a expression was found, compared with those with low concentration of renalase. Patients with simultaneous low miRNA-146a expression and high level of renalase were confirmed to deliver a significantly longer survival time compared with other patients.miRNA-146a and plasma renalase levels were estimated as independent prognostic factors of hemodialyzed patients' survival time. Patients with low miRNA-146a expression demonstrated a significantly longer survival time in contrast to the patients with a high expression level of miRNA-146a. Moreover, a significantly longer survival time was found in patients with high renalase activity compared with patients with low activity of the enzyme