The relationship between stathmin-2 level and metabolic parameters in newly diagnosed type 2 diabetes mellitus patients.

BACKGROUND: Stathmin is a phosphoprotein that plays a role in intercellular and intracellular signalization, inflammation, and differentiation. Our aim was to evaluate the stathmin-2 level and its relationship with the metabolic parameters of newly diagnosed type 2 diabetes mellitus (nT2DM) patients. MATERIAL AND METHOD: This case-control study included 76 patients with nT2DM and 76 healthy individuals with a normal oral glucose tolerance test who were matched for body mass index (BMI), age, and gender. In addition to laboratory and anthropometric measurements related to type 2 diabetes mellitus (T2DM), stathmin-2 levels were determined using an enzyme-linked immunosorbent assay. RESULTS: We observed significantly higher circulating stathmin-2 levels in subjects with T2DM compared to the control group (6.39±1.60 ng/mL and 4.66±0.80 ng/mL, p<0.0001). In patients with metabolic syndrome, circulating stathmin-2 levels were significantly elevated compared to those without metabolic syndrome in both the T2DM and control groups (T2DM: 7.16±1.24 vs 5.06±1.24 ng/mL, p<0.001; Control: 3.84±1.40 vs 3.82±1.40 ng/mL). In both groups, we observed a positive correlation between stathmin-2 levels and BMI and circumference. Moreover, stathmin-2 showed a positive correlation with high-sensitivity C-reactive protein (hs-CRP), homeostatic model assessment of insulin resistance, insulin, fasting blood glucose, hemoglobin A1c, BMI, low-density lipoprotein cholesterol, and total cholesterol. A negative correlation was observed with stathmin-2 and high-density lipoprotein cholesterol. Stathmin-2 did not show any correlation with age, triglyceride, and lactate dehydrogenase. CONCLUSIONS: Stathmin-2 levels were found to be elevated in patients with nT2DM and exhibited positive correlations with hyperinsulinaemia, hyperglycaemia, HOMO-IR and hs-CRP levels. These results indicate that stathmin-2 may play a role in T2DM pathogenesis.

Relationship of Serum Kallistatin Level With Arterial Stiffness and Metabolic Parameters in Obesity-Related Chronic Kidney Disease.

OBJECTIVES: We investigated the relationship between serum kallistatin and kidney disease and proteinuria in nondiabetic obesity-related chronic kidney disease and observed the effects on arterial stiffness. MATERIALS AND METHODS: We included 40 patients with nondiabetic obesity-related chronic kidney disease followed in our nephrology clinic and a control group of 40 participants without chronic kidney disease matched by age, sex, and mean body mass index (measured as weight in kilograms divided by height in meters squared). Pulse-wave velocity and augmentation index were measured oscillometrically by pulse-wave analysis (Mobil-O-Graph) by the same operator. Serum kallistatin levels were measured by sandwich enzyme-linked immunosorbent assay. RESULTS: Mean age of patients was 51 ± 7.5 years (range, 29-62 years), and 40% were female. Mean body mass index was 35 ± 3.1. Four patients (10%) had morbid obesity; 21 (52.5%) had hypertension. Glomerular filtration rate (42 ± 18 vs 83 ± 15 mL/min/1.73 m², respectively; P < .001) were significantly lower. However proteinuria (671 ± 1031 vs 80 ± 30 mg/d, respectively; P < .001) were significantly higher in patients than in controls. Also, serum kallistatin and arterial stiffness were significantly higher in patients (P < .05).''The Pulse Wave Velocity was higher in patients with hypertension (P = .01); GFR was lower (P < .01); serum uric acid level was higher (P < .001); and neutrophil-to-lymphocyte ratio (P < .05), C-reactive protein level (P < .05), and serum kallistatin level were higher (P < .05). CONCLUSIONS: Serum kallistatin levels increase in patients with obesity-related kidney disease. Especially hypertension and hyperuricemia are associated with an increase in serum kallistatin.

Epiregulin: A new prognostic molecule in non-Hodgkin lymphoma.

BACKGROUND: Epiregulin is a molecule that plays a role in cell proliferation, tumor development, inflammation, and angiogenesis in malignant diseases. AIM: Our study aims to reveal, for the first time, the predictive value of this molecule in non-Hodgkin lymphoma (NHL) and its association with disease stage, cell type, and extranodal involvement. METHODS: The study is an observational case-control trial involving 60 newly diagnosed NHL patients and 60 healthy individuals (control group) between 18 and 75 years old. Demographic characteristics of all volunteers, stages of patients' illnesses and lymphoma cell types, hemogram, biochemistry tests, beta 2-microglobulin, C-reactive protein (CRP), and epiregulin levels were measured and statistically evaluated. RESULTS: Epiregulin levels were significantly higher in NHL patients compared to the control group (P < 0.0001). Similarly, a significant increase in epiregulin levels was observed in advanced NHL patients. Furthermore, the most common NHL subgroup within the NHL group, diffuse Large B Cell Lymphoma (DLBCL), and the subgroup with extranodal involvement also had significantly higher levels of epiregulin. A positive correlation was found between the epiregulin molecule and CRP, beta 2-microglobulin, and lactate dehydrogenase (LDH) levels in NHL patients. CONCLUSION: Our study suggests that serum epiregulin levels, discovered to increase in NHL patients for the first time, may be an independent predictive molecule in an advanced stage, extranodal involvement, and the DLBCL subtype of this disease. Epiregulin positively correlates with prognostic molecules such as beta 2-microglobulin, LDH, and CRP. Illuminating its potential role in NHL pathogenesis could make epiregulin a vital drug target for treatment.

Assessment of osteoprotegerin and RANKL levels and several cardiovascular risk scoring systems in acromegaly.

PURPOSE: The OPG/RANKL (osteoprotegerin/receptor activator of nuclear factor kappa-B) system, which plays a crucial role in bone metabolism, is also associated with vascular calcification. Acromegaly is characterized by excessive secretion of growth hormone and insulin-like growth factor, and studies have demonstrated an elevated risk of cardiovascular disease in individuals with acromegaly. In this study, our objective was to investigate the relationship between OPG/RANKL and various cardiovascular risk scoring systems. METHODS: We recruited 44 consecutive acromegaly patients and 41 healthy controls with a similar age and gender distribution for this study. RESULTS: While RANKL levels were significantly higher in the acromegaly group compared to the controls, OPG levels were not found to be significantly different between the two groups. Furthermore, within the acromegaly group, RANKL levels were significantly higher in patients with active acromegaly compared to those with controlled acromegaly. Osteoprotegerin levels showed a positive correlation with the Framingham risk score (FRS) in the acromegaly group. Linear regression analysis revealed an association of OPG with FRS (adjusted R2 value of 21.7%). CONCLUSION: OPG and RANKL may serve as potential markers for assessment of cardiovascular calcification and prediction of the cardiovascular risk status in acromegalic patients.

The level of the neudesin in type-2 diabetic patients and the relationship between the metabolic parameters and carotid intima-media thickness.

BACKGROUND: Neudesin is a protein that is secreted from adipose tissue and central nervous system and has a regulatory function on energy metabolism. Although the effect of this protein is shown in the experimental model of type-2 diabetes mellitus (type-2DM), its effect in humans is not clearly known. In this study, we aimed to evaluate the relationship between serum neudesin level and metabolic, anthropometric and cardiovascular parameters in newly diagnosed type-2DM patients (group 1). METHODS: Forty patients in each were included in our study for group 1 and for the control group (group 2), which consisted of age and sex-matched healthy subjects. Serum neudesin, hs-CRP, carotid intima media thickness (CIMT), Body Mass Index (BMI) and insulin resistance (HOMA-IR) levels were compared prospectively. RESULTS: Serum neudesin levels were significantly higher in diabetic patients than in the control group (type-2DM: 64.69±3.06 ng/mL, control: 55.52±5.48 ng/mL, P=0.004*). There was an independent relationship between serum neudesin and HOMA-IR and BMI. Although there is a correlation between serum neudesin and CIMT; this feature disappeared in the regression analysis. CONCLUSIONS: Serum neudesin increased in new diagnosis type-2DM patients. This increase seems to be related to obesity and insulin resistance. However, more extensive research is needed to clarify this issue.

Associations Between Bioavailable Vitamin D and Remnant Cholesterol in Patients With Type 2 Diabetes Mellitus.

Introduction In circulation, 99% vitamin D is transported by binding to vitamin D binding protein (VDBP) and albumin. Vitamin D at free form and vitamin D binding to albumin are defined as bioavailable vitamin D. Vitamin D deficiency is associated with atherogenic lipid profile and insulin resistance. Remnant cholesterol is defined as the cholesterol component of triglyceride-rich lipoproteins and contributes to the atherosclerotic burden. The aim of this study was to investigate the association between bioavailable vitamin D and remnant cholesterol in patients with type 2 diabetes mellitus (T2DM). Methods A total of 198 T2DM patients and 208 non-diabetic subjects underwent biochemical measurements of lipid profiles, 25(OH)D, VDBP, CRP and albumin levels. Their demographic characteristics (age, sex) were questioned. Subjects with thyroid, kidney and liver dysfunction and using lipid-lowering therapy were not included in the study. The diagnosis of T2DM was made according to the American Diabetes Association ADA 2016 criteria. Classification of vitamin D levels was done according to the Endocrine Society. Bioavailable vitamin D concentrations were calculated. Results High-density lipoprotein cholesterol (HDL), 25(OH)D, free vitamin D and bioavailable vitamin D levels were significantly lower in diabetic patients than in non-diabetic patients while triglyceride, remnant cholesterol and CRP levels were found to be significantly higher. VDBP was positively correlated with CRP and remnant cholesterol in diabetic patients, but not in non-diabetic patients. Cut-off values were determined from non-diabetics as 3.56 ng/mL for bioavailable vitamin D and 26.56 mg/dL for remnant cholesterol. Logistic regression analysis in the control group showed that the odds ratio for increasing remnant cholesterol above the cut-off value was determined as 2.01 for low bioavailable vitamin D and 1.1 for elevated CRP. However, in T2DM there was no significant relationship. In all subjects, low bioavailable vitamin D increased the remnant cholesterol above the cut-off by 2.18-fold independent of the presence of T2DM. However, there was no significant risk to increase remnant cholesterol, considering a total 25(OH) D deficiency in all groups. Conclusions Low bioavailable vitamin D was found to be a risk factor for elevated remnant cholesterol. This relationship was not detected in patients with T2DM. We believe that the inflammation observed in Diabetes Mellitus may increase the concentrations of VDBP and a decrease in bioavailable vitamin D levels. Therefore, measuring VDBP and calculating the bioavailable vitamin D may provide additional information about the actual vitamin D status.

Impact of chemerin, lipid profile, and insulin resistance on disease parameters in patients with multiple sclerosis.

INTRODUCTION: Plasma chemerin, which has chemotactic and adipogenic functions, is increased in several inflammatory diseases. However, its relationship with multiple sclerosis (MS) has not been explored yet. In this study, we aimed to determine chemerin levels and their possible role in MS. METHODS: Chemerin serum concentrations were evaluated by using ELISA kit in 91 clinically definite MS patients and 52 healthy controls. The mean serum chemerin, insulin, and cholesterol levels were compared. Patients were divided into two groups according to the body mass index (BMI), and the relationships between clinical and metabolic parameters were evaluated. RESULTS: Serum chemerin levels were 10.46 ± 1.65 ng/mL in MS patients and 10.26 ± 2.14 ng/mL in the control group. No significant difference was found between patients and controls (p = 0.55). We found no difference regarding age, gender, and BMI between two groups (p = 0.053, p = 0.54, p = 0.41). However, female patients with MS had higher chemerin levels than male patients. There were no associations between serum chemerin levels and EDSS score, annualized relapse rate, BMI, insulin resistance, and serum cholesterol levels in MS patients. CONCLUSION: In this study, we aimed to determine serum chemerin levels in patients with MS. However, in our study, there was no significant difference between serum chemerin levels of MS patients and healthy controls'. Additionally, chemerin levels were not associated with other metabolic parameters, as well as cognitive dysfunction. Further studies are needed to evaluate the role of chemerin in MS patients.

The comparison of analytical performances of Mindray CL-1000i and Beckman Coulter Access II Troponin I methods in the light of recent guidelines and the quality requirements.

BACKGROUND: The results of cardiac troponin I (cTnI) methods used in the diagnosis of acute myocardial infarction (AMI) are highly variable. In this study, it was aimed to compare the analytical performance of the Mindray CL-series TnI method with the Beckman Coulter-Access II AccuTnI+3 method. METHODS: Analytical performance and method comparison experiments for cTnI measurement with Mindray CL-1000i and Beckman Coulter-Access II instruments were with the Clinical and Laboratory Standards Institute (CLSI) documents EP15-A3 and EP9-A3. Precision studies were performed with commercially available third-party quality control (QC) materials. Method comparison experiments were performed by using patient samples. Furthermore, the limit of quantification (LoQ), total analytical error (TAE), and sigma metrics of both methods was determined. RESULTS: The repeatability CV% for the three levels of Mindray CL-series TnI were 1.86, 1.75, and 1.08, while within the laboratory, CV% values were 3.36, 5.27, and 5.82. The quantification limits for Mindray CL-series and Beckman AccuTnI+3 were found to be 0.0085 and 0.0366 ng/mL with a CV level of less than 10%, respectively. The Mindray CL-series TnI results in the method comparison study were higher compared to the Beckman Coulter Access II AccuTnI+3 method. CONCLUSIONS: With low repeatability, low bias, and low LoQ, The Mindray CL-series cTnI method shows it may be used safely in its category. The significant difference between the two methods in the method comparison study reveals cTnI methods in the market should be standardized to ensure global traceability.

Correlation of serum C1q-tumour necrosis factor-related protein 5 levels with metabolic parameters and carotid intima-media thickness in newly diagnosed type 2 diabetes mellitus patients.

PURPOSE: Recent studies have shown that cytokines secreted from adipose tissues play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). CTRP5 (C1q-TNF-related protein 5) is a novel adipokine that has been shown to be associated with glucose and lipid metabolism. Varying levels of CTRP5 have been reported in individuals with diabetes, obesity and coronary artery disease. The aim of this study was to examine serum levels of CTRP5 and to show the relationship with cardiometabolic parameters in T2DM patients. METHOD: The study included 40 T2DM patients and 40 age- and sex-matched healthy control subjects. All the study participants were evaluated with respect to BMI, waist circumference, lipid profile, insulin resistance (HOMA-IR), serum CTRP5 levels, carotid intima-media thickness, and hs-CRP. RESULTS: No statistically significant differences were found between the control group and the diabetic group in terms of age, sex, or BMI. Serum CTRP5 levels (T2DM = 94.55 ± 28.70 ng/ml, control = 76.02 ± 27.22 ng/ml, P = 0.004*) were significantly higher in the group of newly diagnosed diabetic patients. A positive correlation was found between CTRP5 and the cardiometabolic parameters of carotid intima-media thickness (CIMT), hs-CRP, HOMA-IR and BMI. Regression analysis results showed that CTRP5 levels were independently correlated with insulin resistance estimated by HOMA-IR. CONCLUSION: Serum CTRP5 levels were correlated with cardiometabolic parameters and could therefore be a promising indicator of metabolic status and a possible biomarker of insulin resistance. However, the contradictory results reported in different studies indicate the need for further research to assess the significance of CTRP5 for diagnosis and monitoring of treatment efficacy.

Neudesin: a neuropeptide hormone decreased in subjects with polycystic ovary syndrome.

Neudesin is a neuropeptide hormone involves in female reproduction system via promoting effects of progesterone. Polycystic ovary syndrome (PCOS) is a metabolic and reproductive disorder associated with hypothalamic-pituitary-ovarian axis abnormalities and impaired negative feedback mechanism of progesterone upon gonadotropin-releasing hormone secretion. Our aims were to discover whether neudesin levels were altered in PCOS women comparing to controls and to determine the link of neudesin with hormonal-metabolic parameters in PCOS women. The current research was designed as a case-control study. Sixty-eight subjects with PCOS and 67 age- and body mass index (BMI)-matched subjects as controls were enrolled into the study. Circulating neudesin levels were measured by ELISA. Neudesin levels were significantly lower in PCOS subjects compared to controls (4.07 ± 1.22 vs. 6.02 ± 2.07 ng/ml, p < .001). Neudesin exhibited an inversely independent link with luteinizing hormone, free-androgen index, and BMI whereas it showed a positively independent link with progesterone in women with PCOS. Logistic regression analysis revealed that decreased neudesin levels were parallel with increased risk of having PCOS. Decreased neudesin levels were associated with hormonal disturbances in PCOS women, suggesting that neudesin may play a role in pathophysiology of PCOS.

Relation of Decreased Circulating Sortilin Levels With Unfavorable Metabolic Profiles in Subjects With Newly Diagnosed Type 2 Diabetes Mellitus.

BACKGROUND: Sortilin, a pluripotent peptide hormone, plays a role in glucose and lipid metabolism. A link between sortilin and insulin sensitivity has been implicated. However, the clinical implications of this link remain elusive. Our aims were to investigate whether sortilin levels were altered in subjects with newly diagnosed type 2 diabetes mellitus (nT2DM) compared with subjects with normal glucose tolerance (NGT) and to determine whether a link exist between sortilin levels and metabolic parameters. MATERIALS AND METHODS: A total of 150 subjects including 75 nT2DM patients and 75 subjects with NGT who were matched in age, body mass index, and sex were enrolled into this case-control study. The circulating levels of sortilin were measured using enzyme-linked immunosorbent assay. A 2-hour 75-g oral glucose tolerance test was used for diagnosis of T2DM. Metabolic parameters of enrolled subjects were also determined. RESULTS: The circulating levels of sortilin were found to be significantly lower in subjects with nT2DM than in controls (138.44 ± 38.39 vs. 184.93 ± 49.67 pg/mL, P < 0.001). Sortilin levels showed a negative correlation with insulin resistance and unfavorable lipid profiles, while they were positively correlated with high-density lipoprotein cholesterol in subjects with nT2DM. Linear regression analysis showed an independent and inverse link between sortilin and insulin resistance and unfavorable lipid profiles. Moreover, logistic regression analysis revealed that the subjects with the lowest sortilin levels had an increased risk of nT2DM compared with those subjects with the highest sortilin levels. CONCLUSIONS: Decreased circulating levels of sortilin were associated with unfavorable metabolic profiles in subjects with nT2DM.

Increased urocortin 3 levels are associated with the risk of having type 2 diabetes mellitus.

BACKGROUND: Urocortin 3 (UCN3) is a peptide hormone playing a pivotal role in glucose and lipid metabolisms. However, its clinical implications remain unclear. Our aims were to investigate the altered levels of UCN3 in newly diagnosed type 2 diabetes mellitus (nT2DM) patients in comparison to subjects with normal glucose tolerance (NGT) and to determine the presence of any possible link between UCN3 levels and metabolic parameters. METHODS: Eighty nT2DM and 80 age-, body mass index (BMI)-, and gender-matched NGT subjects were enrolled into this case-control study. The circulating UCN3 levels were measured using the enzyme-linked immunoabsorbent assay (ELISA). Metabolic parameters of enrolled subjects were also determined. A standard 75-g 2-hour oral glucose tolerance test was used for diagnosis of type 2 diabetes mellitus (T2DM). RESULTS: UCN3 levels were higher in subjects with nT2DM than in controls (115.64 ± 39.26 vs 86.16 ± 22.81 pg/mL, P < .001). UCN3 levels were increased in subjects with metabolic syndrome compared to subjects without metabolic syndrome in both nT2DM and NGT groups. UCN3 levels showed a positive correlation with BMI in both groups. Moreover, UCN3 levels were positively and independently associated with insulin, fasting blood glucose, insulin resistance, 2-hour plasma glucose, glycosylated hemoglobin, and triglycerides, whereas UCN3 levels were negatively and independently associated with high-density lipoprotein cholesterol. According to logistic regression analysis, increased risk of T2DM and metabolic syndrome were parallel with the highest elevated levels of UCN3. CONCLUSIONS: Increased levels of UCN3 are associated with unfavorable metabolic profiles in T2DM, indicating a potential role of UCN3 in glucose and lipid metabolisms in T2DM.

Assessment of subclinical atherosclerotic cardiovascular disease in patients with ankylosing spondylitis.

OBJECTIVE: The aim of the present study was to compare patients with ankylosing spondylitis (AS) with healthy controls with respect to subclinical atherosclerotic cardiovascular disease (CVD). METHODS: A total of 44 patients with AS with no history of CVD, diabetes mellitus, hypertension, chronic kidney disease, and lipid-lowering drug use were compared with 40 age- and sex-matched healthy controls with respect to carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), which are surrogate markers of subclinical atherosclerosis. Correlation analysis was also performed to examine the association between surrogate markers and disease activity with inflammation [Ankylosing spondylitis disease activity score with C-reactive protein (ASDAS-CRP)]. RESULTS: In addition to age and sex, both groups were comparable with respect to cigarette smoking, body mass index, and high-density lipoprotein cholesterol (p=0.425, p=0.325, and p=0.103, respectively). The level of total cholesterol was significantly lower in patients with AS (p=0.002). Nonsteroidal anti-inflammatory drug and tumor necrosis factor alpha inhibitor use ratios in patients with AS were 79.5% and 65.9%, respectively. There was no significant difference between both groups regarding PWV and CIMT (p=0.788 and p=0.253, respectively). In patients with AS, there was a significant correlation between ASDAS-CRP and CIMT (r=0.315, p=0.038), but the correlation between ASDAS-CRP and PWV was not significant (r=-0.183, p=0.234). CONCLUSION: The results of the present study could not provide sufficient evidence whether disease activity with inflammation caused subclinical atherosclerotic CVD in patients with AS without overt CVD. The increased atherosclerotic CVD risk is most probably multifactorial in patients with AS, but the extent of the contribution of disease activity with inflammation to increased atherosclerosis is controversial.

Evaluation of Analytical Performance of Variant II Turbo HbA1c Analyzer According to Sigma Metrics.

BACKGROUND: Hemoglobin A1c, (HbA1c) which is the major constituent of glycated hemoglobin, has been used in the follow-up of retrospective glycemia for years and in the diagnosis of diabetes mellitus nowadays. Since the analytical performance of HbA1c should be high likewise all laboratory tests, various quality control measures are used. Sigma metrics is one of these measures and it is the combination of bias, precision and total allowable error that ensures a general evaluation of analytical quality. The aim of our study was to evaluate the analytical performance of Bio-Rad's Variant Turbo II HbA1c analyzer according to sigma metrics. METHODS: Sigma levels were calculated using the data obtained from two levels of internal and 12 external quality control materials (Bio-Rad) of Variant II Turbo HbA1c analyzer according to σ = (TEa% - Bias%) / CV% formula. RESULTS: The mean sigma levels for low and high quality control materials were found to be 3.0 and 4.1, respectively. CONCLUSIONS: The annual mean analytical performance of Variant II Turbo HbA1c analyzer was found to be acceptable according to sigma metrics. In order to be sure of the difference in HbA1c results indicating the success or failure in treatment but not arise from analytical variation, it is thought that more stringent quality control measures should be applied to reach higher sigma levels.

Association of decreased C1q/tumor necrosis factor-related protein-5 levels with metabolic and hormonal disturbance in polycystic ovary syndrome

Objective: C1q/tumor necrosis factor-related protein-5 (CTRP5) is a novel peptide hormone involved in the metabolism of energy regulation. Polycystic ovary syndrome (PCOS), which is a reproductive and metabolic disorder, is associated with insulin resistance. The aim of the current study was to compare circulating levels of CTRP5 in women with and without PCOS and to investigate possible associations between CTRP5 and metabolic-hormonal parameters. Material and Methods: The present cross-sectional study contained 80 women with PCOS and 80 age and body mass index-matched women without PCOS. Circulating levels of CTRP5 were calculated using an enzyme-linked immunosorbent assay. We also measured hormonal and metabolic parameters. Results: Patients with PCOS had lower levels of circulating CTRP5 compared with women without PCOS (6.90±2.64 vs 11.73±3.66 ng/mL, p<0.001). CTRP5 was negatively correlated with insulin resistance, free-androgen index, and body mass index in both the PCOS and control groups. Moreover, patients with PCOS who had insulin resistance showed lower circulating CTRP5 levels compared with those without insulin resistance. In both the control and PCOS groups, overweight subjects had lower circulating levels of CTRP5 compared with participants of normal weight. Logistic regression analyses indicated that subjects in the lowest tertile for CTRP5 level had higher risk for PCOS compared with those in the highest tertile of CTRP5. Conclusion: Decreased circulating levels of CTRP5 were associated with higher risk of PCOS, as well as having metabolic disturbance among women with PCOS.

Evaluation of maternal serum ischemia modified albumin and total antioxidant status in ectopic pregnancy.

BACKGROUND: Ectopic pregnancies constitute about 2% of all pregnancies which are the leading cause of pregnancy-related deaths and a considerable cause of maternal morbidity. Oxidative stress can lead to a number of pregnancy related diseases including miscarriage, eclampsia and preterm labor. Ischemia modified albumin (IMA) which reflects the oxidative stress may be used as a marker for ectopic pregnancy. Our aim was to compare the levels of IMA and total antioxidant status (TAS) in ectopic and normal pregnancies and to understand if IMA can be used as a marker to diagnose ectopic pregnancy. MATERIALS AND METHODS: Our case-control study consisted of 38 women with ectopic and 42 women with normal pregnancy. IMA and TAS levels were determined in serum samples with an albumin-cobalt binding test and by commercially available kits, respectively. IMA levels were adjusted according to serum albumin levels. Index of oxidation (IOS) was calculated by dividing adjusted IMA (A-IMA) levels with TAS. A receiver operating characteristics (ROC) curve analysis was made and cut-off values for the biomarkers were investigated in SPSS 21.0 program (SPSS, Chicago, IL). Data were presented as mean ± standard deviation and a p value < .05 was accepted as statistically significant. RESULTS: There was a statistically significant difference in IMA, A-IMA, and IOS levels between ectopic and normal pregnancies. Although TAS level was not different statistically, it was lower in ectopic pregnancy. According to ROC curve analysis, IOS had the largest area under curve. A cut-off value of 0.545 for IOS had 81.6% sensitivity and 59.5% specificity. CONCLUSIONS: According to our study, oxidative stress plays an important role in ectopic pregnancy and either A-IMA or IOS can be evaluated as a marker of ectopic pregnancy after further studies.

The low levels of bone morphogenic protein-4 and its antagonist noggin in type 2 diabetes.

OBJECTIVE: Bone morphogenic protein-4 (BMP-4) is a proinflammatory cytokine which is controlled by BMP-4 antagonists. Our aim was to investigate the levels of BMP-4 and its antagonists, noggin and matrix Gla protein (MGP), in prediabetes and diabetes. DESIGN: One hundred and forty-two type 2 diabetic, 32 prediabetic, and 58 control subjects participated in this cross-sectional study. BMP-4, noggin, and MGP were measured with the ELISA method. RESULTS: There was a significant difference between the three groups in relation to sex, hypertension, fasting plasma glucose, HbA1c, lipid profiles, and diastolic blood pressure (p < 0.05). BMP-4 levels were significantly lower in the diabetic group compared to the control group (108.5 and 127.5 ng/mL, respectively, p < 0.001 diabetes vs. control). Noggin levels were significantly lower in the diabetic group compared to the prediabetic and control groups (10.5, 11.5, and 12.0 ng/mL, as median, respectively, p < 0.001; diabetes vs. control, p = 0.002; diabetes vs. prediabetes). BMP-4 was associated significantly with noggin in the entire study population (ß coefficient = 0.796, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve was 0.708 (95% CI 0.551-0.864, p = 0.011) for BMP-4 levels. The optimal cutoff value of BMP-4 for detecting albuminuria was 118.5 ng/mL for which sensitivity was 71.4% and specificity was 66.4%. CONCLUSIONS: BMP-4 and noggin levels were lower in the diabetic group. High BMP-4 levels were significantly associated with albuminuria. Further studies are warranted to determine the role of BMP-4 in the pathogenic processes underlying albuminuria and hyperglycemia in patients with type 2 diabetes.

Matrix metalloproteinase-9, 10, and stress hyperglycaemia in acute kidney injury.

BACKGROUND: This study investigated the effect of matrix metalloproteinase (MMP)-9 and 10, and stress hyperglycaemia on the necessity of emergency renal replacement therapy (RRT) and mortality in nondiabetic geriatric patients with acute kidney injury (AKI). MATERIALS AND METHODS: The present observational and longitudinal study included 101 nondiabetic geriatric patients (age >65 years) with AKI. The serum levels of MMP-9 and MMP-10 were evaluated in these patients. Serum glucose level >140 mg/dL at the time of admission was accepted as stress hyperglycaemia. RESULTS: The average age of patients was 81 ± 7.1 years. Stress hyperglycaemia was diagnosed in 34.6% of the cases; the majority of these cases were patients with high-serum urea, CRP, and chronic kidney disease. The average levels of MMP-9 and MMP-10 were found to be 199 ± 38 and 16.5 ± 7.5 ng/mL, respectively. Thirty-one cases (30.6%) mortality during hospitalization and 20 cases (20%) underwent emergency RRT. Multiregression analysis showed the serum urea (P < .001) and stress hyperglycaemia (P = .03) to be independently associated with mortality. Also, serum urea (P = .01), potassium level (P = .03), and MMP-10 levels (P = .03) were independently associated with the necessity of the emergency RRT. The MMP-9 levels exhibited no relation with the necessity of emergency RRT and mortality. CONCLUSION: Stress hyperglycaemia is a common condition among nondiabetic geriatric patients with AKI and is related to mortality. Serum MMP-10 levels serve as an important predictor of the necessity of emergency RRT in these patients.

Relationship Between Serum Macrophage Migration Inhibitory Factor Level and Insulin Resistance, High-Sensitivity C-Reactive Protein and Visceral Fat Mass in Prediabetes.

BACKGROUND: Growing evidence suggest that macrophage migration inhibitory factor (MIF) plays a vital role in glucose metabolism. We aimed to ascertain whether MIF levels are altered in subjects with prediabetes and also to determine the relationship between MIF and metabolic parameters as well as visceral fat mass. MATERIAL AND METHODS: This cross-sectional study included 40 subjects with prediabetes and 40 age-, body mass index (BMI)- and sex-matched subjects with normal glucose tolerance. Circulating MIF levels were measured using enzyme-linked immunosorbent assay. Metabolic parameters of recruited subjects were evaluated. Visceral fat mass was measured using bioelectrical impedance method. RESULTS: Circulating MIF levels were found to be elevated in subjects with prediabetes compared to controls (26.46 ± 16.98 versus 17.44 ± 11.80 ng/mL, P = 0.007). MIF positively correlated with BMI, visceral fat mass and indirect indices of homeostasis model assessment of insulin resistance. In linear regression model, an independent association was found between MIF levels and metabolic parameters, including BMI, visceral fat mass and homeostasis model assessment of insulin resistance. Multivariate logistic regression analyses revealed that the odds ratio for prediabetes was higher in subjects in the highest quartile of MIF compared to those in the lowest quartile, after adjusting for potential confounders. CONCLUSIONS: Increased MIF levels are associated with the elevation of prediabetic risk.

Relationship between insulin resistance, hs-CRP, and body fat and serum osteoprotegerin/RANKL in prediabetic patients.

BACKGROUND: Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPN) are soluble members of the tumor necrosis factor superfamily. Growing evidence suggest that there is link between inflammation, insulin resistance and OPG, soluble RANKL (sRANKL). We aimed to ascertain whether OPG and sRANKL levels are altered in prediabetic subjects and there is association between OPG/sRANKL and metabolic parameters. METHODS: Forty prediabetic subjects and 40 age- and BMI-matched controls were recruited for this cross-sectional study. Circulating OPG, sRANKL were measured using ELISA. Anthropometric and metabolic parameters were also determined. RESULTS: Circulating sRANKL (97.74±17.67 vs. 55.00±11.19 pg/mL, P=0.010) and OPG (261.54±74.55 vs. 159.23±52.91 pg/mL, P=0.020) levels were found to be significantly higher in diabetic subjects compared with control subjects. There was a positive correlation between sRANKL and OPG. sRANKL also positively correlated with BMI, insulin resistance marker HOMA-IR, inflammatory marker hs-CRP. Logistic regression analyses revealed that the odds ratio was increased for prediabetes in subjects with having elevated sRANKL levels. CONCLUSIONS: Increased sRANKL and OPG levels were associated with prediabetic subjects. sRANKL and OPG may play a role in the pathogenesis of diabetes as well as metabolic disturbance.