Introduction: Medullary thyroid cancer (MTC) is characterized by overexpression of cholecystokinin-2/gastrin receptors (CCK2R). There are limitations of calcitonin as a tumor marker in MTC diagnosis and prognosis. Procalcitonin is gaining a role as a complementary tumor marker. This study aimed to assess the feasibility of procalcitonin measurements on top of the calcitonin measurements after CCK2R agonist stimulation in patients with MTC. Material and methods: The assessment was part of the GRAN-T-MTC translational study conducted through a Phase I multicenter clinical trial in patients with locally advanced and/or disseminated MTC. Patients were administered intravenously the CCK2R agonist CP04 labelled with indium-111 ([In-111]In-CP04); the first four patients at a lower mass amount of 10 mu g, and afterwards the whole group at a higher mass amount of 50 mu g. Blood samples for calcitonin and procalcitonin measurements were obtained shortly before and 2, 5, 10, and 20 minutes after start of [In-111]In-CP04 administration. Results: Sixteen patients were included in the study. After injection of the higher mass amount of [In-111]In-CP04, the median maximum ratio for stimulated calcitonin was 2.97 (interquartile range [IQR] 2.35) pg/mL and procalcitonin 2.01 (IQR 2.07) pg/mL. The maximum stimulated/baseline calcitonin ratio was 5.2 +/- 4.0 and 4.1 +/- 3.8 in the low and high mass amount groups, respectively, and the maximum stimulated/baseline procalcitonin ratio was 4.6 +/- 5.1 and 2.9 +/- 3.1 in the low and high mass amount groups, respectively. There was a significant linear correlation between calcitonin and procalcitonin concentrations (p < 0.001) at each test time point and between the maximum procalcitonin and maximum calcitonin increment ratio (r = 0.94, p < 0.0001). Mild, short-lasting side effects (transient tachycardia, flushing) were observed in one patient during the injection of low and in two patients during the injection of high mass amount of [In-111] In-CP04. The side effects were not related to the baseline calcitonin or procalcitonin concentrations. Conclusion: Procalcitonin concentrations after CP04 stimulation were highly correlated with calcitonin concentrations. Unlabeled CP04, if available commercially, may be considered an alternative stimulating agent in MTC patients, even in lower mass amounts. Further studies, including healthy controls, are required to prove this concept and calculate the diagnostic thresholds.

INTRODUCTION:Medullary thyroid cancer (MTC) is a rare malignant tumour of the parafollicular C-cells with an unpredictable clinical course and currently suboptimal diagnostic and therapeutic options, in particular in advanced disease. Overexpression of cholecystokinin-2 receptors (CCK2R) represents a promising avenue to diagnostic imaging and targeted therapy, ideally through a theranostic approach. MATERIALS AND METHODS:A translational study (GRAN-T-MTC) conducted through a Phase I multicentre clinical trial of the indium-111 labelled CP04 ([111In]In-CP04), a CCK2R-seeking ligand was initiated with the goal of developing a theranostic compound. Patients with proven advanced/metastatic MTC or short calcitonin doubling time were enrolled. A two-step concept was developed through the use of low- and high-peptide mass (10 and 50 μg, respectively) for safety assessment, with the higher peptide mass considered appropriate for therapeutic application. Gelofusine was co-infused in a randomized fashion in the second step for the evaluation of potential reduction of the absorbed dose to the kidneys. Imaging for the purpose of biodistribution, dosimetry evaluation, and diagnostic assessment were performed as well as pre-, peri-, and postprocedural clinical and biochemical assessment. RESULTS:Sixteen patients were enrolled. No serious adverse events after application of the compound at both peptide amounts were witnessed; transient tachycardia and flushing were observed in two patients. No changes in biochemistry and clinical status were observed on follow-up. Preliminary dosimetry assessment revealed the highest dose to urinary bladder, followed by the kidneys and stomach wall. The effective dose for 200 MBq of [111In]In-CP04 was estimated at 7±3 mSv and 7±1 mSv for 10 μg and 50 μg CP04, respectively. Administration of Gelofusine reduced the dose to the kidneys by 53%, resulting in the organ absorbed dose of 0.044±0.019 mSv/MBq. Projected absorbed dose to the kidneys with the use of [177Lu]Lu-CP04 was estimated at 0.9±0.4 Gy/7.4 GBq. [111In]In-CP04 scintigraphy was positive in 13 patients (detection rate of 81%) with superior diagnostic performance over conventional imaging. CONCLUSION:In the present study, [111In]In-CP04 was shown to be a safe and effective radiopharmaceutical with promising theranostic characteristics for patients with advanced MTC.

Introduction. Matrix Gla proteins (MGPs) are usually considered as natural inhibitors of soft tissue calcification in chronic inflammatory disorders. However, MGP levels in acute inflammation related to myocardial ischemia have been poorly investigated. This study aimed to compare the serum concentrations of uncarboxylated MGPs (ucMGPs) between patients with ST-segment elevation myocardial infarction (STEMI) vs. with chronic coronary syndromes (CCS) and to investigate the association between ucMGP concentration and an increased risk of major adverse cardiovascular events (MACE) in STEMI patients. Material and methods. 155 consecutive patients were enrolled (mean ± standard deviation age, 64 ± 13 years), including 80 patients with a first STEMI and 75 ones with CCS as controls. Blood samples were obtained within the first 24 h from hospital admission to evaluate ucMGP levels. Combination of MACE [all-cause mortality, heart failure (HF) within the first 30 days after myocardial infarction] was evaluated. Results. ucMGP levels were higher in patients with STEMI than in controls (2929 ± 96.5 ng/mL vs. 67.3 + 32.3 ng/mL; p < 0.0001). A significant positive correlation between ucMGP and high-sensitivity C-reactive protein, troponin levels was found. Multivariate analysis showed that ucMGP was an independent associate of STEMI [odds ratio (OR) 1.39; confidence interval (CI): 0.78–2.14, p = 0.01]. Although ucMGP did not predict the combined MACE, however it was an independent associate of HF occurrence 30 days after STEMI (OR, 1.20; 95% CI: 1.07–1.30, p = 0.04). Conclusion. Elevated ucMGP levels in patients with STEMI indicate that some MGPs may be involved in disorders related not only to chronic but also acute inflammatory states.

Introduction: The relationship between the gut and skeleton is increasingly recognized as a component of the regulation of carbohydrate metabolism. The aim of our study was to assess the relationship between bone mineral density (BMD), incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), intestinotrophic peptide glucagon-like peptide-2 (GLP-2) and osteocalcin isoforms in patients with long-term type 1 diabetes (T1D) when compared to healthy controls. Methods: Eighty two patients with long term T1D, treated in the Department of Metabolic Diseases and 53 healthy controls were recruited to the study. Long term disease duration was defined as lasting for more than 10 years. The control group was selected among age- and sex-matched healthy people. Fasting blood samples were collected to measure levels of incretin hormones (GLP-1, GLP-2, GIP), two forms of osteocalcin (uncarboxylated (ucOC), and carboxylated (cOC)), and additional biochemical parameters associated with glucose and bone metabolism (HbA1c, calcium, phosphorus, 25(OH)D3, PTH). Results: Patients with T1D had higher BMI than in controls (p = 0.02). There was no difference in BMD at the lumbar spine and the femoral neck between patients with long-term T1D and healthy ones. Z-score values in both groups were within normal ranges. The level of GIP was significantly higher in T1D patients (p = 0.0002) in comparison to the healthy ones. The levels of GLP-1 and GLP-2 did not differ between T1D patients and controls. In the T1D group, strong, positive associations were found between serum levels of GLP-1 and cOC (r = 0.546, p < 0.001) and between GLP-1 and total OC (r = 0.51, p < 0.001), also after adjusting for BMI (p < 0.001 and p < 0.001, respectively). Significant positive associations were also found between serum levels of GLP-2 and cOC (r = 0.27, p = 0.013) and between GLP-2 and total OC (r = 0.25, p = 0.018), also in a multivariate regression (p = 0.009, p = 0,175, respectively). Moreover, in T1D patients, GLP-1 correlated positively with the femoral neck BMD (g/cm(2)) (r = 0.265, p = 0.016) and this association was statistically significant after adjusting for BMI (p = 0.011). These correlations were not present in the control group. The only significant correlation observed in the control group was between OC and BMD of the neck (p = 0.049 for neck BMD g/cm(2), and p = 0.041 for neck Z-score). Conclusions: Our data suggests an effect of gut hormones on bone in long-term T1D, which could be associated with OC activity, however we did not find a direct connection with glucose metabolism. GLP-1 could have a possible, protective role on bone mineral density in patients with T1D. The data from our study suggests that gut hormones could be considered as a new link in the skeleton - pancreatic endocrine loop in patients with T1D.

BACKGROUND:Chronic kidney disease is linked to cardiovascular morbidity; therefore, relevant biomarkers are widely investigated.AIMS:We aimed to assess the relationship between nitric oxide (as measured by its metabolites, NOx), a key endothelial molecule, with markers of endothelial dysfunction, inflammation, antioxidant status, and mineral disorders as well as histologically assessed vascular calcification in uremic and hemodialysis patients with chronic kidney disease.METHODS:Plasma and serum samples were obtained from 62 patients with renal failure. NOx was assessed by the Griess method, while the other biomarkers were measured by the immunoenzymatic assay. Morphological analysis of arterial calcification was performed in a blinded, semiquantitative manner. Common carotid intima‑media thickness and atherosclerotic plaques were assessed by ultrasonography.RESULTS:In the simple analysis, NOx levels correlated positively with the parameters of renal function, mineral metabolism, endothelial injury, and inflammation. NOx predicted carotid intima‑media thickness in simple (P = 0.014) and multiple analysis (P = 0.036) adjusted for the Framingham risk score, C‑reactive protein, serum creatinine, and parathormone. The occurrence of atherosclerotic plaques in the common carotid artery was correlated with higher NOx concentrations (P = 0.021).CONCLUSIONS:In chronic renal failure, NOx is associated with surrogate markers of atherosclerosis, even after adjustment for traditional cardiovascular risk factors, inflammation, and renal function, but not with the presence or grade of medial arterial calcification. Endothelial injury, inflammation, and mineral metabolism markers are associated with NOx levels, though a causal link requires further study.

Background: Endothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. Patients: 80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-beta (TGF-beta), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1 alpha (SDF1 alpha) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. Results: After adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1 alpha, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1-3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions. Conclusion: Among novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.

Poster: EANM 19 / EPS-077 / Phase I clinical trial using a novel CCK2 receptor-localizing radiolabelled peptide probe for personalized diagnosis and therapy of patients with progressive or metastatic medullary thyroid carcinoma - final results by: Hubalewska-Dydejczyk1, R. Mikolajczak2, C. Decristoforo3, P. Kolenc-Peitl4, P. A. Erba5, K. Zaletel4, H. Maecke6, T. Maina7, M. W. Konijnenberg8, P. Garnuszek2, M. Trofimiuk-Muldner9, E. Przybylik-Mazurek9, I. Virgolini3, M. de Jong8, A. C. Froberg8, C. Rangger3, G. Goebel3, L. Scarpa3, B. Glowa10, K. Skorkiewicz10, L. Lezaic4, B. Solnica9, D. Fedak9, P. Gaweda9, A. Sowa-Staszczak9, B. A. Nock7, D. Bergant4, S. Rep4, V. Lenda-Tracz10; 1Jagiellonian University, Endocrinology Dep, Nuclear Med. Unit, KRAKOW, POLAND, 2NCBJ POLATOM, Otwock-Swierk, POLAND, 3Medical University, Innsbruck, AUSTRIA, 4University Medical Center, Ljubljana, SLOVENIA, 5University of Pisa, Pisa, ITALY, 6University Medical Center, Freiburg, GERMANY, 7National Center for Scientific Research Demokritos, Athens, GREECE, 8Erasmus MC, Rotterdam, NETHERLANDS, 9Jagiellonian University, Krakow, POLAND, 10University Hospital, Krakow, POLAND

INTRODUCTION The prevalence of cardiovascular (CV) comorbidity in patients with chronic kidney disease (CKD) is high, particularly in end-stage renal disease (ESRD). There is an ongoing search for novel biomarkers of CV disease in this population. OBJECTIVES We aimed to investigate the associations of matrix proteoglycans (PGs) and glycosaminoglycans (GAGs), collagen, and arterial calcifications with selected serum and plasma markers of endothelial dysfunction, inflammation, oxidative stress, and bone turnover in patients with ESRD. PATIENTS AND METHODS We enrolled 47 adult patients (32 men) with stage 5 CKD. The following parameters were investigated: fibrinogen, soluble thrombomodulin (sTM), plasminogen activator inhibitor 1 (PAI-1), stromal cell-derived factor 1 alpha (SDF-1 alpha), calcium (Ca), phosphate (Pi), intact parathormone, interleukin 6, high-sensitivity C-reactive protein (hs-CRP), ferric reducing ability of plasma, 2,2-diphenyl-1-picrylhydrazyl scavenging, ferric reducing ability of ascorbate in plasma, fetuin-A, fibroblast growth factor 23, osteopontin, osteoprotegerin, osteocalcin, transforming growth factor beta (TGF-beta), hepatocyte growth factor, secreted protein acidic and rich in cysteine, as well as matrix metalloproteinase 2. Radial artery specimens were stained with alizarin red for calcifications, alcian blue for PGs and GAGs, and sirius red for collagen. RESULTS We observed positive correlations between PG and GAG, collagen, and calcification staining. The most intense (grade 3) alcian blue staining was significantly correlated with diabetes as well as higher levels of Ca x Pi product, hs-CRP, fibrinogen, SDF-1 alpha, PAI-1, and sTM. However, PAI-1 was the only significant predictor of grade 3 alcian blue staining in a multiple logistic regression model adjusted for hemodialysis, Ca x Pi product, and hs-CRP levels. CONCLUSIONS Coagulation disorders and endothelial dysfunction are the hallmarks of ESRD. The levels of SDF-1 alpha, PAI-1, sTM, and fibrinogen may be novel predictors of early vascular wall alterations and may serve as CV risk markers.

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima-media thickness (CCA-IMT). Moreover, we studied the relationship between OPG levels and all-cause and cardiovascular (CV) mortality during a 5-year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C-reactive protein, interleukin-6, tumor necrosis factor receptor II (TNFRII), transforming growth factor-, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA-IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39-20.4; P=0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA-IMT values (OR 6.56; 95%CI 1.06-40.6; P=0.036). OPG levels above the median were associated with higher CCA-IMT values (1.02 +/- 0.10 vs. 0.86 +/- 0.13; P<0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84-72.9; P<0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA-IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow-up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA-IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all-cause mortality in CKD patients with advanced medial arterial calcification.

Carboxylated osteocalcin (Gla-OC) contributes to the bone formation, whereas its undercarboxylated form (Glu-OC) takes part in the energy metabolism. In vitro studies had shown that treatment of osteoblast-like cells with advanced glycation end product-modified bovine serum resulted in reduced synthesis of collagen 1 and osteocalcin. The aim of this study was to find association between Gla-OC and markers of protein glycation, oxidation and nitration, as well as pro-inflammatory and antioxidant defense markers in obese subjects. Non-obese [(body mass index (BMI)<30 kg/m; n=34)] and obese subjects (30<BMI <40 kg/m2; n=98), both sexes, aged 25 to 65 years, were included in this study. Urinary glycation, oxidation and nitration free adduct concentrations were determined by stable isotopic dilution analysis liquid chromatography and mass spectrometry, and normalized to creatinine. Obese subjects had lower Gla-OC serum levels when compared to the non-obese controls. Obese subjects had increased serum concentrations of insulin, C reactive protein, interleukin 6, leptin and insulin resistance index (HOMA IR). Urinary early glycation and advanced glycation end product (AGE) free products, Nε-fructosyl-lysine and 3-deoxyglucosone-derived hydroimidazolone, respectively, and oxidative damage marker, N-formylkynurenine free adduct, were increased in the obese compared to the non-obese subjects. Serum Gla-OC was negatively correlated with urinary methylglyoxal-derived AGE, hydroimidazolone MG-H1, and N-formylkynurenine free adducts. The Gla-OC/Glu-OC index negatively correlated with the MG-H1 free adduct, and correlated positively with the antioxidant defense marker - the glutathione peroxidase activity. Our results suggest that increased AGEs and protein oxidative damage markers in the course of obesity may contribute to decreased Gla-OC level and, consequently, future risk of decreased bone formation.

INTRODUCTION:The aim of the study was to assess the arterial stiffness and serum levels of selected metalloproteinases (MMPs) in hypertensive patients and their changes following antihypertensive therapy.MATERIAL AND METHODS:The study group consisted of 95 patients with essential arterial hypertension (HT) stage 1 or 2 (mean age: 53.1 ±13.0 years). The control group consisted of 31 normotensives of the same age range. Hypertension patients were randomized to one of the following monotherapies for 6 months: quinapril, losartan, amlodipine, hydrochlorothiazide or bisoprolol. Carotid-femoral pulse wave velocity (PWV) was measured using a Complior device. Serum concentrations of MMPs (proMMP-1, MMP-2, MMP-3, MMP-9) and plasma concentration of tissue inhibitor of MMPs (TIMP-1) were measured using ELISA.RESULTS:Pulse wave velocity and serum concentrations of MMP-2 and MMP-9 were higher in HT patients than in the control group. In HT patients PWV was significantly associated (R2 = 0.41) with age (B = 0.408, p = 0.00027), systolic blood pressure (SBP) (B = 0.441, p = 0.0011), and MMP-3 (B = 0.204, p = 0.0459). After 6 months of treatment, regardless of the agent used, we observed a significant decrease of PWV, SBP, MMP-2 and MMP-3 and an increase of TIMP-1 plasma concentration. The decrease of PWV was significantly associated with a decrease of SBP (R2 = 0.07, B = 0.260, p = 0.015) only.CONCLUSIONS:In patients with arterial hypertension, beside age and systolic blood pressure, the determinants of arterial stiffness include serum MMP-3 concentration. For drugs compared in the study with the same hypotensive effect obtained, the arterial stiffness reduction effect is not dependent on the drug used. Systolic blood pressure is one of the independent factors responsible for the reduction of arterial stiffness in the course of antihypertensive treatment.

BACKGROUND:Difficulties in diagnosis of inflammatory bowel disease (IBD) motivate the search for new diagnostic tools, including laboratory tests. The aim of this study was to evaluate concentrations of the neutrophil (NEU) proteins leukocyte elastase (HLE-α1AT), lactoferrin and calprotectin as potential biomarkers used in the diagnosis and assessment of clinical activity of Crohn's disease (CD) and ulcerative colitis (UC).MATERIAL/METHODS:The study included 27 patients with CD, 33 patients with UC and 20 healthy controls. Plasma concentrations of calprotectin, lactoferrin and HLE-α1AT were measured using ELISA.RESULTS:In patients with CD higher concentrations of HLE-α1AT (64.3±43.1 vs. 30.1±7.7 ng/l, P<0.001), calprotectin (151.6±97.8 vs. 69.9±22.1 ng/l, P<0.001) and lactoferrin (243.2±102.0 vs. 129.7±32.7 ng/l, P<0.001) than in the control group were found. In patients with UC higher plasma concentrations of HLE-α1AT (62.0±30.9 vs. 30.1±7.7 ng/l, P<0.001), calprotectin (149.6±72.3 vs. 69.9±22.1 ng/l, P<0.001) and lactoferrin (242.6±107.5 vs 129.7±32.7 ng/l, P<0.001) than in the control group were found. HLE-α1AT/NEU and lactoferrin/NEU ratios in patients with UC were significantly higher compared with patients with CD. Calprotectin (P=0.010) and lactoferrin (P=0.023) levels were higher in patients with the active compared with inactive phase of CD.CONCLUSIONS:The diagnostic characteristics of plasma granulocyte protein concentrations indicate the usefulness of these tests in the diagnosis of IBD. Higher HLE-α1AT and lactoferrin/NEU ratios in patients with UC than with CD may suggest the usefulness of these ratios in differential diagnostics. Plasma calprotectin and lactoferrin levels may be useful in CD activity assessment.

Purpose. During the transition from premenopause to postmenopause, many women experience weight gain and central fat deposition; therefore, we hypothesized that circulating growth factors can play a role in the pathogenesis of hypertension, metabolic syndrome, and subclinical organ damage in perimenopausal women.Basic Procedures. The study included 192 women aged 40 to 60 years; 152 had newly diagnosed essential hypertension that had never been treated, and 40 were normotensive age-matched controls. For all subjects, 24-h ambulatory blood pressure monitoring (ABPM), echocardiographic examination with assessment of left ventricular mass (LVM) and systolic and diastolic functions (GE Vivid 7.0, General Electric Vingmed Ultrasound, Horten, Norway), carotid ultrasound with measurement of intima-media thickness, and carotid femoral pulse wave velocity (PWV) measurement (SphygmoCor, AtCor Medical, Sydney, Australia) were performed. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 2 (IGFBP-2), and insulin-like growth factor-binding protein 3 (IGFBP-3) were measured using an immunochemical assay.Main Findings. Hypertensive women had significantly lower IGFBP-2 levels than did normotensive controls (162.9 +/- 83.7 vs. 273.1 +/- 103.0 mu g/L, p < 0.001); the groups did not differ regarding IGF and IGFBP-3 concentrations. After adjusting the covariates, multivariate analysis showed that IGFBP2 was significantly negatively correlated with 24-h systolic blood pressure (beta = -0.31, p = 0.02). The adjusted odds ratio for hypertension per standard deviation decrease in IGFBP-2 was 3.43 (95% confidence interval [CI] 1.65-7.13). IGFBP-2 showed a negative correlation with the number of metabolic syndrome components. Independent of body composition, IGFBP-2 was significantly related to left ventricular relative wall thickness and the ratio of mitral inflow velocities as parameter of diastolic function.Principal Conclusions. In perimenopausal women, decreased IGFBP-2 levels may play a role in blood pressure regulation and the development of subclinical left ventricular diastolic dysfunction. Whether IGFBP-2 is a marker or a mediator of cardiovascular disease in this population merits further investigation. (C) 2017 Elsevier Inc. All rights reserved.

Purpose Disrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin. Patients and methods The cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined. Results In total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta=0.22; p=0.016 and beta=0.26; p=0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age. Conclusions Our data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis.

Introduction:Fetuin-A plays an important role in bone turnover and vascular calcification.Aim:The aim of the study was to assess the relationship between serum fetuin-A concentrations, inflammatory and bone turnover markers of patients on maintenance hemodialysis.Materials and Methods:The study was performed in 71 patients (21 women, 40 men) aged 60 ± 12 years on chronic dialysis because of end-stage renal failure for a period of 75 ± 57.2 months. The routine laboratory tests were performed with Modular P analyzer (Roche Diagnostics), serum concentrations of iPTH were measured using Nichols method, hsCRP and IL-6 using nephelometric techniques while fetuin-A, bone-specific alkaline phosphatase (bALP), fully carboxylated osteocalcin (cOC), undercarboxylated osteocalcin (ucOC), and fibroblast growth factor-23 (FGF-23) were measured using commercially available ELISA kits.Results:Concentrations of fetuin-A were significantly positively correlated with albumin (r=0.37, p=0.003) and negatively associated with patients age (r=26, p=0.04), log (iPTH) (r=0.31, p=0.02), log (CRP) (r=0.31, p=0.02), log (IL-6) (r=0.41, p=0.001), log (ucOC) (r=-0.29, p=0.02), and log (FGF-23) (r=0.27, p=0.04).Conclusions:1. Patients on maintenance hemodialysis suffer from severe disturbances of bone turnover. 2. Low serum fetuin-A levels are associated with increase markers of bone turnover and inflammation.

AIMS:Diabetes is considered a state of increased oxidative stress. This study evaluates blood concentrations of selected markers of antioxidant defense in patients with type 2 diabetes.METHODS:The study included 80 type 2 diabetes patients and 79 apparently healthy controls. Measured markers included ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamyltransferase (GGT) and uric acid serum, and plasma and/or hemolysate levels.RESULTS:FRAP, uric acid, CRP, and GGT levels were significantly higher in patients with diabetes. Plasma and hemolysate GR was significantly higher whereas GPx activity was significantly lower in patients with diabetes. There were no significant differences in antioxidant defense markers between patients with and without chronic diabetes complications. Fasting serum glucose correlated with plasma GPx, plasma and hemolysate GR, FRAP, and serum GGT, and HbA1c correlated with serum GGT. Only FRAP and serum uric acid were significantly higher in obese (BMI > 30 kg/m(2)) patients with diabetes than in nonobese patients.CONCLUSIONS:Some components of antioxidant defense such as GR, uric acid, and GGT are increased in patients with type 2 diabetes. However, the whole system cannot compensate for an enhanced production of ROS as reflected by the trend toward decreased erythrocytes GSH.

BACKGROUND:Carboxylated osteocalcin (Gla-OC) participates in bone remodeling, whereas the undercarboxylated form (Glu-OC) takes part in energy metabolism. This study was undertaken to compare the blood levels of Glu-OC and Gla-OC in nonobese, healthy obese, and prediabetic volunteers and correlate it with the metabolic markers of insulin resistance and early markers of inflammation.METHODS:Nonobese (body mass index [BMI] <30 kg/m2 ; n = 34) and obese subjects (30 <BMI <40 kg/m2 ; n = 98), both sexes, aged 25 to 65 years, were divided into healthy control, normal weight subjects, healthy obese, and obese with biochemical markers of prediabetes. The subgroups with obesity and low or high Gla-OC or Glu-OC were also considered for statistical analysis. After 2 weeks of diet standardization, venous blood was sampled for the determination of Gla-OC, Glu-OC, lipid profile, parameters of inflammation (hsCRP, interleukin 6, sE-selectin, sPECAM-1, and monocyte chemoattractant protein 1), and adipokines (leptin, adiponectin, visfatin, and resistin).RESULTS:Gla-OC in obese patients was significantly lower compared to nonobese ones (11.36 ± 0.39 vs 12.69 ± 0.90 ng/mL, P = .048) and weakly correlated with hsCRP (r = -0.18, P = .042), visfatin concentration (r = -0.19, P = .033), and BMI (r = -0.17, P = .047). Glu-OC was negatively associated with fasting insulin levels (r = -0.18, P = .049) and reduced in prediabetic individuals compared with healthy obese volunteers (3.04 ± 0.28 vs 4.48 ± 0.57, P = .025).CONCLUSIONS:Decreased blood concentration of Glu-OC may be a selective early symptom of insulin resistance in obesity, whereas the decreased level of Gla-OC seems to be associated with the appearance of early markers of low grade inflammation accompanying obesity.