Hulya Yalcin

Biomarkers and cytokines of bone turnover: extensive evaluation in a cohort of patients with ankylosing spondylitis

BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory disease of spine and sacroiliac joints; it is characterized by new bone formation, and the disease processes can be accompanied by osteoporosis. In the present study, we investigated changes in bone mineral density (BMD) and in the levels of various bone turnover-related biomarkers and cytokines in a cohort of AS patients, with regard to clinical parameters, disease activity, and treatment regimen.Methods55 AS patients and 33 healthy controls included in the study. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI), and radiologic changes were scored by the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Patients were also evaluated with the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Bone mineral density (BMD) assessed by dual energy X-ray absorptiometry. Various biomarkers and cytokines of bone turnover including osteoprotegerin (OPG), serum band 5 tartrate-resistant acid phosphatase (TRAP-5), soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), and sclerostin were studied.ResultsThe levels of TRAP-5, NTX, sRANKL, sclerostin, sFRP-1, DKK-1, and IFNγ, were similar between the patients and controls (p > 0.05), while BMD of femoral neck, and OPG levels were significantly lower in AS patients (p < 0.05). In a subgroup analysis, patients with active disease had significantly higher concentrations of OPG compared with the inactive group. Rest of the biomarkers and cytokines of bone turnover were similar between the active and inactive disease groups. Subgroup analysis of patients receiving anti-TNFα agents and conventional therapy revealed that OPG concentrations were significantly lower in the patients receiving biological drugs, while BAP and DKK-1 were significantly higher in the patients treated with conventional agents.ConclusionsIn this cross-sectional study we showed that OPG levels were significantly lower in AS patients compared to healthy subjects. On the other hand, the levels of wingless (Wnt) signal pathway inhibitors seem not altered. Ectopic bone formation in AS may be related to dysfunction of these molecules at the cellular level.

Postload hyperglycemia is associated with increased subclinical inflammation in patients with prediabetes.

Abstract Background/aims. In this present study, we aimed: (i) To clarify if prediabetes is associated with subclinical inflammation independent of underlying obesity, and (ii) to evaluate the effect of postload glucose concentration on subclinical inflammation markers in a group of patients with elevated fasting glucose. Material and methods. In a cohort of 165 patients with newly detected fasting hyperglycemia, according to 75 g oral glucose tolerance test (OGTT), subjects were classified either as newly diagnosed type 2 diabetes (diabetes group, n = 40), impaired fasting glucose (IFG) plus impaired glucose tolerance (IGT) (IFG/IGT group, n = 42) or IFG only (IFG group, n = 83). A control group (n = 47) consisted of age- and body mass index (BMI)-matched healthy subjects with a normal OGTT. Circulating concentrations of lipids, insulin, interleukin-6 (IL-6), interleukin-8 (IL-8) and high sensitive C-reactive protein (hsCRP) were measured. HOMA index was calculated. Results. Subclinical inflammation markers were elevated in patients with diabetes and IFG/IGT compared to healthy controls and also IFG patients (diabetes vs. control: p < 0.05 for hsCRP, IL-8, and IL-6; IFG/IGT vs. control: p < 0.05 for hsCRP, and IL-6; diabetes vs. IFG: p < 0.05 for hsCRP, and IL-6; IFG/IGT vs. IFG: p < 0.05 for hsCRP, and IL-6). In multiple regression analysis, postload glucose concentration was independently associated with circulating hsCRP and IL-6 concentrations when the data was controlled for age, gender, BMI and lipid concentrations (p < 0.05 for hsCRP, and IL-6). Conclusion. Our results suggest that patients with prediabetes, independent of underlying obesity, have increased concentrations of subclinical inflammation which is mostly driven by postload glucose concentrations.

S1000A12, Chitotriosidase, and Resolvin D1 as Potential Biomarkers of Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterised by periodic inflammatory attacks. We investigated changes in monocyte-granulocyte derived S10012A and chitotriosidase in both the attack and silent period of FMF for better estimation of inflammation. Endogenous resolvin was determined for utility to restrict inflammation. This study included 29 FMF patients (15 M/14 F) and 30 healthy controls (15 M/15 F). Serum levels of highly sensitive C-reactive protein, serum amiloid A (SAA), S100A12, chitotriosidase, and resolvin D1 were measured. Age, sex, body mass indexes, and lipids were similar between patients and controls. Biomarkers including hs-CRP, SAA, S100A12, chitotriosidase, and resolvin D1 were higher in the attack period of FMF patients compared to controls (P < 0.001). When FMF patients in the silent period were compared with their attack period, hs-CRP, SAA, and chitotriosidase were found elevated in the attack period (P < 0.001, P < 0.001, and P = 0.02 respectively). Serum levels of SAA, S100A12, chitotriosidase, and resolvin D1 in the silent period of FMF patients were still found elevated compared to healthy controls, indicating subclinical inflammation (P < 0.001, P < 0.001, P = 0.009, and P < 0.001 respectively ). In subgroup analysis, patients with M694V homozygote and heterozygote mutations had higher S10012A and hs-CRP compared to other mutation carriers. Our findings indicate that chitotriosidase and S10012A are useful in diagnosis and detection of subclinical inflammation and/or assessment of disease activity in FMF patients. They could be more informative for inflammation in various disease states compared to hsCRP and SAA. Resolvin D1 is elevated in both the attack and silent periods of FMF. It may be helpful to restrict inflammation. Graphical Abstract

The effect of sleeve gastrectomy on serum irisin levels in patients with morbid obesity

INTRODUCTION Irisin, a recently identified myokine, is associated with increased energy expenditure and has a potential role in obesity. Therefore, we investigated circulating irisin levels in morbidly obese patients undergoing sleeve gastrectomy (SG). MATERIAL AND METHODS Thirty morbidly obese patients undergoing SG and 30 healthy subjects were included. All participants were evaluated at baseline and again at three months post-SG. Body weight and height, the lipid profile, and plasma glucose, HbA1c, insulin, and irisin levels were measured at each visit. RESULTS The two groups had similar mean age and sex distribution. Serum irisin was significantly lower in the morbidly obese subjects compared with the controls (p = 0.003) and negatively correlated with BMI, body weight, insulin levels, and HOMA-IR (p = 0.006, p = 0.011, p = 0.046, p = 0.048, respectively). When the morbidly obese patients were re-evaluated three months post-SG, their weight and BMI had significantly decreased (both p = 0.001). Similarly, the insulin, HbA1c, HDL-cholesterol, and HOMA-IR values significantly decreased (p = 0.001, p = 0.028, p = 0.006, and p = 0.001, respectively). However, irisin levels remained unchanged (p = 0,267). CONCLUSION Although the irisin levels were significantly lower in the morbidly obese subjects, they did not change after SG-induced weight loss. (Endokrynol Pol 2016; 67 (5): 481-486).

No association of serum PSA with vitamin D or total oxidant-antioxidant capacity in healthy men

Abstract Background and aim: Vitamin D deficiency and oxidative stress were suggested to be related to prostate cancer risk. We aimed to investigate the association of serum PSA concentration with vitamin D and total oxidant/antioxidant levels. Materials and methods: A total of 95 healthy men were enrolled for the cross sectional study. Serum PSA, 25(OH)D, serum total oxidant status, and total antioxidant status were measured. Results: Serum PSA was significantly negatively correlated with serum total oxidant status (r= −0.309, p = .003) but there was no significant correlation between PSA and 25(OH)D (p = .383) or total antioxidant levels (p = .233). After adjustment for age BMI and smoking status with multiple regression analysis, there was no significant association between serum PSA and total oxidant status. Conclusion: We find no evidence for an association between PSA and vitamin D levels or serum total oxidant/antioxidant levels.

The independent relationship between hemoglobin A1c and homeostasis model assessment of insulin resistance in non-diabetic subjects

Abstract Introduction: Determining the factors affecting hemoglobin A1c (HbA1c) levels may help better interpretation of HbA1c values. In this study, we investigated if insulin resistance is a significant parameter contributing to the variability of HbA1c values. Methods: We retrospectively analyzed serum fasting glucose, fasting insulin, 2 h glucose and HbA1c records of 18–85 years aged outpatients who underwent a 75 g oral glucose tolerance test (OGTT) in our hospital during the period January 2010–May 2014. Homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.5 was defined as insulin resistant. Results: Insulin resistant subjects with normal glucose tolerance had significantly higher HbA1c and fasting glucose levels compared to insulin sensitive subjects with normal glucose tolerance (p=0.002, p<0.001, respectively). Similarly, insulin resistant subjects with pre-diabetes had significantly higher HbA1c and 2-h glucose levels compared to insulin sensitive subjects with pre-diabetes (p=0.016, p=0.013, respectively). Regression analysis showed that HOMA-IR(log) is associated with HbA1c levels independent of fasting and 2h glucose concentrations (p<0.001). Age was the variable with highest standardized β coefficient in regression model. Conclusion: Our data showed that HOMA-IR is associated with glycated hemoglobin values independent of glycemic status and the effect of age on HbA1c values should not be ignored in non-diabetic subjects.

EDTA interference in electrochemiluminescence ACTH assay.

Background As plasma is the recommended sample type for Roche adrenocorticotropic hormone (ACTH) assay, we evaluated the effect of EDTA concentration on Cobas ACTH assay. Methods Samples containing twofold and fourfold higher concentrations of EDTA were prepared by adding plasma to empty K2EDTA tubes and by making under-filled EDTA tubes. All measurements were performed with four replicates. Results Increased EDTA concentration resulted in a significant decrease in ACTH concentration. Fifty-per cent-filled EDTA tube showed 19% decrease in ACTH concentration and 25% filled EDTA tube showed 50% decrease in ACTH concentration. Conclusion We recommend that inadequately filled EDTA specimens should be rejected when using Cobas ACTH assay.