Are total bilirubin and high-sensitivity C-reactive protein independently associated with Type 2 diabetes mellitus in postmenopausal women?

BACKGROUND: Various studies have reported contradictory results regarding the relationship of total bilirubin and high-sensitivity C-reactive protein levels (hsCRP) with diabetes mellitus Type 2 (DM2). Therefore, we aimed to examine which one of them could be more convenient for the estimation of DM2 risk in postmenopausal women. MATERIALS AND METHODS: A total of 150 healthy postmenopausal women (mean age 57[53-60] years) and 79 postmenopausal women with DM2 (mean age 66 [61-71] years) were enrolled in cross-sectional study. Examinees were recruited consecutively in the study during their regular check-up visit in the Primary Health Care Center in Podgorica, Montenegro, in a period from October 2012 to May 2016. Anthropometric measurements, biochemical parameters, and blood pressure were obtained. Multivariable logistic regression analysis was used to find the independent predictors for DM2 development in postmenopausal women. RESULTS: Age, waist circumference, and total bilirubin were the independent predictors for DM2 development in postmenopausal women (odds ratio [OR] =1.224, 95% confidence interval [CI] [1.117-1.341], P < 0.001; OR = 1.137, [95% CI = 1.036-1.215], P < 0.001, and OR = 0.727, [95% CI = 0.611-0.866], P < 0.001, respectively), whereas hsCRP lost its independent predictive role (OR = 1.155, [95% CI = 0.854-1.560], P = 0.349). CONCLUSION: Unlike hsCRP, total bilirubin independently correlated with DM2 in postmenopausal women.

CARDIOMETABOLIC RISK AMONG MONTENEGRIN URBAN CHILDREN IN RELATION TO OBESITY AND GENDER.

Considering previously reported discrepant results in the literature, we aimed to investigate the impact of gender and overweight/obesity on cardiometabolic risk (CMR) among Montenegrin urban children. The cross-sectional study included random sample of 201 schoolchildren aged 7-12 years (64% of boys) from Podgorica. Children's nutritional status was determined according to the International Obesity Task Force criteria. CMR was assessed using a sum of z values of the following five indicators: glucose, total cholesterol, inverted value of high-density lipoprotein cholesterol, triglycerides, and hypertension. Higher CMR was found among both overweight and obese boys compared to normal weight boys (p<0.001). The effect size of the difference in CMR between overweight and obese girls and normal weight counterparts was less prominent (p<0.05). Logistic regression analysis revealed that body mass index was independent predictor of high CMR [odds ratio (OR)=1.06; 95% confidence interval (CI)=1.02-1.10); p=0.002]. On the contrary, we found no impact of socioeconomic status, physical activity or sedentary time on CMR in the examined cohort of schoolchildren. In conclusion, both overweight and obesity even among young population are related to higher CMR and this effect is more prominent among boys as compared to girls.

Lipid profile and left ventricular geometry pattern in obese children.

BACKGROUND: Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular and all-cause mortality. Previous studies reported conflicting results concerning the relationship between serum lipid levels and left ventricular geometry pattern. We sought to explore the relationship between standard serum lipid profile measures with left ventricular geometry pattern in obese children. PATIENTS AND METHODS: In this cross-sectional study, a total of 70 obese children were examined. Fasting blood samples were taken to measure total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TGs), glucose, and insulin. Based on these values TG/HDL ratio, BMI and HOMA index were calculated. We also measured the average 24-h ambulatory systolic blood pressure (SBP) and two-dimensional (2/D) transthoracic echocardiography was performed to determine left ventricular mass index (LVMI) and relative wall thickness (RWT). Multiple regression analyses were conducted to explore relationships between study variables and the LVMI or RWT as outcome variables. The final model with LVMI included TG/HDL ratio, BMI, 24 h-average SBP, age and sex, while for the RWT we included BMI, insulin, age and sex. RESULTS: Our study included 70 children (65.71% boys and 34.29% girls) median age (14 years, IQR = 12-16)." We demonstrated independent and positive association of TG/HDL ratio, BMI and 24 h-average SBP with LVMI (effect = 3.65, SE = 1.32, p < 0.01; effect = 34.90, SE = 6.84, p < 0.01; effect = 0.32, SE = 0.12, p < 0.01, respectively). On the other hand, in model with RWT as outcome variable, only BMI and insulin were significantly linked (BMI: effect = 13.07, SE = 5.02, p = 0.01 Insulin: effect = 2.80, SE = 0.97). CONCLUSION: Increased TG/HDL ratio in obese children is associated with the development of eccentric left ventricular hypertrophy while increased BMI and insulin were associated with concentric left ventricular hypertophy.

Body mass index is independently associated with xanthine oxidase activity in overweight/obese population.

PURPOSE: The pathophysiological mechanism of the relationship between xanthine oxidase (XO) activity and obesity has not been completely elucidated. Since inflammation and oxidative stress are regarded as key determinants of enlarged adipose tissue, we aimed to investigate the association between oxidative stress (as measured with XO activity), inflammation [as measured with high-sensitivity C-reactive protein (hsCRP)] and obesity [as measured with body mass index (BMI)]. In addition, we wanted to examine whether hsCRP itself plays an independent role in XO activity increase or it is only mediated through obesity. METHODS: A total of 118 overweight/obese volunteers (mean age 54.76 ± 15.13 years) were included in the current cross-sectional study. Anthropometric, biochemical parameters, and blood pressure were obtained. RESULTS: Significant differences between age, BMI, waist circumference, concentrations of uric acid and hsCRP, as well as xanthine dehydrogenase (XDH) activities were evident among XO tertile groups. Multiple linear regression analysis revealed that BMI (beta = 0.241, p = 0.012) and XDH (beta = - 0.489, p < 0.001) are the independent predictors of XO activity (R2-adjusted = 0.333), whereas hsCRP lost its independent role in XO activity prediction. CONCLUSION: Obesity (as determined with increased BMI) is an independent predictor of high XO activity in overweight/obese population. LEVEL OF EVIDENCE: Level V: cross-sectional descriptive study.

Are visceral adiposity index and lipid accumulation product reliable indices for metabolic disturbances in patients with type 2 diabetes mellitus?

BACKGROUND: Visceral adiposity index (VAI) and Lipid accumulation product (LAP) are novel visceral adiposity indexes, proposed for the evaluation of cardiometabolic risk in adult population. Considering contradictory results obtained from many studies so far, we aimed to examine the potential benefit of applicability of VAI and LAP, over simple anthropometric indices and traditional lipid parameters in individuals with type 2 diabetes mellitus (DM2). METHODS: A total of 180 DM2 (of them 50% females) and 119 controls who volunteered to participate in this cross-sectional study were enrolled. Anthropometric and biochemical parameters, as well as blood pressure were obtained. VAI and LAP were calculated. RESULTS: Multivariate logistic regression analysis showed that high-density lipoprotein cholesterol (HDL-c), (P<.001), waist circumference (WC), (P=.027), age (P=.001), hypolipemic therapy (P=.024), and LAP (P=.005) were independent predictors of DM2 in adjusted models. In Receiver Operating Characteristic curve analysis, used to discriminate subjects with DM2 from those who did not have it, good accuracy of the applied procedures was only achieved with models which were consisted of parameters used in VAI (Body mass index, WC, HDL-c, triglycerides) and LAP (WC, triglycerides) indexes equations, respectively [Area under the curve (AUC)=0.819 and AUC=0.800, respectively], but not with VAI (AUC=0.781) and LAP (AUC=0.784) indexes themselves. CONCLUSION: Visceral adiposity index and Lipid accumulation product may not be better than parameters that enter its equation in type 2 diabetes prediction.

Visceral Adiposity Index is not Superior over Anthropometric Parameters with regards to Inflammation in Healthy Adolescent Girls.

OBJECTIVE: Better than simple anthropometric parameters, the visceral adiposity index (VAI) has recently been proposed as a predictor of cardiometabolic risk in adults. However, there are conflicting results on the associations of these parameters in children and adolescents. Therefore, we aimed to estimate this potential relationship between VAI, anthropometric parameters (i.e., body mass index [BMI], waist circumference [WC], and waist-to-height ratio [WHtR], respectively), and inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) levels in a cohort of adolescent girls. METHODS: A total of 90 adolescent girls from 16 to 19 years old were included in cross-sectional study. Anthropometric and biochemical parameters (glucose, lipid parameters, and hsCRP) were measured. The VAI, derived from anthropometric and lipid parameters, calculated {[WC/36.58 + (1.89 × BMI)] × (triglycerides/0.81) × (1.52/HDL-cholesterol)} was calculated. RESULTS: A comparison of the receiver operating characteristic (ROC) curves showed that all the curves for the anthropometric parameters (e.g., BMI, WC, WHtR) had excellent discriminatory capability with regard to inflammation level status (low vs. high level) and significantly larger areas under the curve (AUC = 0.885, AUC = 0.863, AUC = 0.860, respectively; P < 0.001) than the ROC curve for VAI did (AUC = 0.686; P = 0.021). CONCLUSION: Visceral adiposity index is not superior over anthropometric parameters in relation to inflammation as measured by high sensitivity C-reactive protein in adolescent girls.

The association between follicle stimulating hormone and glutathione peroxidase activity is dependent on abdominal obesity in postmenopausal women.

PURPOSE: Menopause is frequently associated with an increase in visceral fat, thus modifying redox status by promoting oxidative damage and decreasing antioxidant defense systems. It is known that at higher concentrations estradiol has some antioxidant properties, while its decline in postmenopause is associated with pro-oxidant effects. However, the role of follicle stimulating hormone (FSH) in antioxidant defense in postmenopausal women is still not well elucidated. Therefore, we aimed to evaluate the potential complex association between visceral obesity, FSH and enzymatic antioxidant defense as measured by glutathione peroxidase (GPx) in postmenopausal women. METHODS: A total of 150 postmenopausal women (mean age 56.6 ± 4.8 years), among them 50 normal weight and 100 overweight/obese, were included. GPx activity, FSH, luteinizing hormone, estradiol, total testosterone, cardiometabolic and anthropometric parameters, were determined. RESULTS: With increasing tertiles of serum FSH levels, significant increase in GPx activity (P = 0.005) was found. Also, the highest number of overweight/obese subjects were in the group with the lowest FSH values (χ 2 = 14.9, P < 0.001). After multiple linear regression analysis, the relationship between GPx and FSH disappeared, whereas only higher waist circumference (ß = -0.218, P = 0.045) predicted lower FSH level (adjusted R 2 = 0.227). CONCLUSION: Higher GPx activity is associated with higher FSH level, but abdominal obesity may be the underlying determinant of this relationship.

Retinol-binding protein 4 versus albuminuria as predictors of estimated glomerular filtration rate decline in patients with type 2 diabetes.

BACKGROUND: Since the increase in some tubular damage biomarkers can be observed at the early stage of diabetic nephropathy, even in the absence of albuminuria, we aimed to investigate if urinary albumin is superior than tubular damage marker, such as serum retinol-binding protein 4 (RBP4), in predicting renal function decline (defined as estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) in the cohort of patients with type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: A total of 106 sedentary T2D patients (mean [± standard deviation] age 64.9 [±6.6] years) were included in this cross-sectional study. Anthropometric and biochemical parameters (fasting glucose, glycated hemoglobin [HbA1c], lipid parameters, creatinine, RBP4, high sensitivity C-reactive protein [hsCRP], urinary albumin excretion [UAE]), as well as blood pressure were obtained. RESULTS: HsCRP (odds ratio [OR] =0.754, 95% confidence interval [CI] (0.603-0.942), P = 0.013) and RBP4 (OR = 0.873, 95% CI [0.824-0.926], P < 0.001) were independent predictors of eGFR decline. Moreover, although RBP4 and UAE as single diagnostic parameters of renal impairment showed excellent clinical accuracy (area under the curve [AUC] = 0.900 and AUC = 0.940, respectively), the Model which included body mass index, HbA1c, triglycerides, hsCRP, and RBP4 showed statistically same accuracy as UAE, when UAE was used as a single parameter (AUC = 0.932 vs. AUC = 0.940, respectively; P for AUC difference = 0.759). As well, the Model had higher sensitivity and specificity (92% and 90%, respectively) than single predictors, RBP4, and UAE. CONCLUSION: Although serum RBP4 showed excellent clinical accuracy, just like UAE, a combination of markers of tubular damage, inflammation, and traditional markers has the higher sensitivity and specificity than UAE alone for prediction renal impairment in patients with T2D.

The Association Between Retinol-Binding Protein 4 and Cardiovascular Risk Score is Mediated by Waist Circumference in Overweight/Obese Adolescent Girls

Retinol-binding protein 4 (RBP4) is an emerging risk factor for atherosclerotic disease in adults. However, to our knowledge, there are no studies examining the relationship between RBP4 and cardiovascular risk in young population. Therefore, we aimed to estimate this potential relationship in overweight/obese adolescent girls. Seventy overweight/obese adolescent girls, mean age 17.6±1.20 years, were included. Anthropometric and biochemical parameters were measured. Cardiovascular risk score (CVRS) was calculated by adding points for each risk factor (e.g., sex, high-density lipoprotein cholesterol (HDL-c), non-HDL-c, smoking, blood pressure and fasting glycemia). According to the risk status, we divided adolescent girls into low, medium and high risk groups (-2≤ CVRS ≤1, 2≤ CVRS ≤4 and CVRS ≥5, respectively). We found significantly higher RBP4 in the high risk group as compared with low risk group (p<0.001). However, multiple linear regression analysis showed waist circumference (beta=0.257, p=0.031) to be the only independent predictor of higher cardiovascular risk (adjusted R(2)=0.342, p<0.001). In conclusion, RBP4 may be associated with higher cardiovascular risk in overweight/obese adolescent girls, but this association is mediated by abdominal obesity.

Association between unfavorable lipid profile and glycemic control in patients with type 2 diabetes mellitus.

BACKGROUND: Recent studies hypothesize that dyslipidemia can predict glycated hemoglobin (HbA1c) and could be important contributing factor to the pathogenesis of type 2 diabetes mellitus (DM2). Therefore, we aimed to evaluate the influence of lipid parameters on long-term glycemic control in DM2. MATERIALS AND METHODS: A total of 275 sedentary DM2 (mean [±standard deviation] age 60.6 [±10.0] years) who volunteered to participate in this cross-sectional study were enrolled. Anthropometric (body weight, body hight, and waist circumference), biochemical parameters (fasting glucose, HbA1c, lipid parameters, creatinine), as well as blood pressure were obtained. RESULTS: Total cholesterol (odds ratio [OR] =1.30, 95% confidence interval [CI] [1.02-1.66], P = 0.032), triglycerides (OR = 1.34, 95% CI (1.07-1.67), P = 0.010), and low density lipoprotein cholesterol (OR = 1.42, 95% CI [1.10-1.83], P = 0.006) were the independent predictors of higher HBA1c, and as they increased by 1 mmol/L each, probabilities of higher HBA1c increased by 30%, 34%, and 42%, respectively. Low level of high-density lipoprotein cholesterol (HDL-c) was found to be the independent predictor of higher HBA1c (OR = 0.44, 95% CI [0.20-0.67], P = 0.039), and increase in HDL-c by 1 mmol/L, reduced the probability of higher HBA1c by 56%. CONCLUSION: Unfavorable lipid profile can predict HbA1c level in DM2 patients. Early diagnosis of dyslipidemia, as well as its monitoring and maintaining good lipids control can be used as a preventive measure for optimal long-term glycemic control.

Serum soluble transferrin receptor levels are independently associated with homeostasis model assessment of insulin resistance in adolescent girls.

Introduction: Markers of iron homeostasis are related to insulin resistance (IR) in adults. However, studies in children and adolescents are scarce and show contradictory results. The aim was to evaluate the potential relationship between iron status markers and IR. Additionally, no previous study has explored the mutual effect of biomarkers of iron homeostasis and inflammation (i.e. high sensitivity C-reactive protein (hsCRP)), and adipokines (i.e. retinol-binding protein 4 (RBP4)) on IR in the cohort of adolescent girls. Material and methods: A total of 60 girls age between 16 and 19 years were included in the study. Serum levels of ferritin, transferrin, soluble transferrin receptor (sTfR), hsCRP, and RBP4 were measured by immunonephelometry. Homeostasis model assessment of insulin resistance (HOMA-IR) and iron homeostasis indexes were calculated. Univariate and multivariate binary logistic regression analysis were used to investigate the possible independent associations of the examined biomarkers. Principal component analysis was used to examine their mutual effect on HOMA-IR in the studied girls. Results: Ferritin, sTfR, hsCRP and RBP4 were significant predictors for higher HOMA-IR in univariate analysis (p = 0.020, p = 0.009, p = 0.007, p = 0.003, respectively). Multivariate regression analysis after adjustment for waist circumference (WC) showed that serum sTfR levels remained positively associated with higher HOMA-IR (p = 0.044). Factorial analysis revealed that the obesity-inflammation related factor (i.e., WC and hsCRP) and adipokine-acute phase protein related factor (i.e., RBP4 and ferritin) showed significant differences between HOMA-IR < 2.5 and HOMA-IR ≥ 2.5. Conclusions: Serum sTfR levels are independently associated with HOMA-IR, whereas higher serum ferritin levels together with higher RBP4 are related to higher HOMA-IR in adolescent girls.

Oxidative stress and cardiometabolic biomarkers in patients with non-alcoholic fatty liver disease.

Oxidative stress is assumed to be the underlying feature of non-alcoholic fatty liver disease (NAFLD). To our knowledge, the mutual involvement of redox status homeostasis parameters [i.e., advanced oxidation protein products (AOPP), pro-oxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS) and oxidative-stress index (OSI)] and cardiometabolic biomarkers in subjects with NAFLD has not been examined yet. Accordingly, we aimed to investigate this potential relationship. A total of 122 subjects with NAFLD were compared with 56 participants without NAFLD. The diagnosis of NAFLD was confirmed by abdominal ultrasound. Anthropometric and biochemical parameters were measured. OSI, Castelli's Risk Index I (CRI-I) and Castelli's Risk Index II (CRI-II) were calculated. Univariate and multivariate binary logistic regression analysis were used to test the predictions of oxidative stress and cardiometabolic markers, respectively for NAFLD. Principal component analysis (PCA) was applied to explore its mutual effect on NAFLD status. Significant positive associations of CRI-I, CRI-II, high sensitivity C-reactive protein (hsCRP) and AOPP with NAFLD were found. PCA analysis extracted 3 significant factors: Oxidative stress-cardiometabolic related factor (i.e., triglycerides, AOPP, HDL-c and HbA1c)-explained 36% of variance; Pro-oxidants related factor (i.e., TOS and PAB)-explained 17% of variance; and Antioxidants related factor (i.e., TAS)-explained 15% of variance of the tested parameters. Moreover, binary logistic regression analysis revealed significant predictive ability of Oxidative stress-cardiometabolic related factor (p < 0.001) and Pro-oxidants related factor (p < 0.05) for NAFLD status. In addition to oxidative stress (i.e., determined by higher AOPP levels), dyslipidemia (i.e., determined by higher lipid indexes: CRI-I and CRI-II) and inflammation (determined by higher hsCRP) are independently related to NAFLD status. The mutual involvement of pro-oxidants (i.e., TOS and PAB), or the joint involvement of pro-oxidants (i.e., AOPP) and cardiometabolic parameters (i.e., HbA1c, triglycerides and HDL-c) can differentiate subjects with NAFLD from those individuals without this metabolic disorder. New studies are needed to validate our results in order to find the best therapeutic approach for NAFLD.

Factorial Analysis of the Cardiometabolic Risk Influence on Redox Status Components in Adult Population.

Different byproducts of oxidative stress do not always lead to the same conclusion regarding its relationship with cardiometabolic risk, since controversial results are reported so far. The aim of the current study was to examine prooxidant determinant ((prooxidant-antioxidant balance (PAB)) and the marker of antioxidant defence capacity (total sulphydryl groups (tSHG)), as well as their ratio (PAB/tSHG) in relation to different cardiometabolic risk factors in the cohort of adult population. Additionally, we aimed to examine the joint effect of various cardiometabolic parameters on these markers, since to our knowledge, there are no studies that investigated that issue. A total of 292 participants underwent anthropometric measurements and venipuncture procedure for cardiometabolic risk factors assessment. Waist-to-height ratio (WHtR), body mass index, visceral adiposity index (VAI), and lipid accumulation product (LAP) were calculated. Principal component analysis (PCA) grouped various cardiometabolic risk parameters into different factors. This analysis was used in the subsequent binary logistic regression analysis to estimate the predictive potency of the factors towards the highest PAB and tSHG values. Our results show that triglycerides, VAI, and LAP were positively and high density lipoprotein cholesterol (HDL-c) were negatively correlated with tSHG levels and vice versa with PAB/tSHG index, respectively. On the contrary, there were no independent correlations between each cardiometabolic risk factor and PAB. PCA revealed that obesity-renal function-related factor (i.e., higher WHtR, but lower urea and creatinine) predicts both high PAB (OR = 1.617, 95% CI (1.204-2.171), P < 0.01) and low tSHG values (OR = 0.443, 95% CI (0.317-0.618), P < 0.001), while obesity-dyslipidemia-related factor (i.e., lower HDL-c and higher triglycerides, VAI, and LAP) predicts high tSHG values (OR = 2.433, 95% CI (1.660-3.566), P < 0.001). In conclusion, unfavorable cardiometabolic profile was associated with higher tSHG values. Further studies are needed to examine whether increased antioxidative capacity might be regarded as a compensatory mechanism due to free radicals' harmful effects.

Serum endocan levels in relation to traditional and non-traditional anthropometric indices in adult population.

BACKGROUND: Association between endocan and nontraditional anthropometric indices, as distinct cardiovascular disease risk factors, has not been examined in previous studies. Endocan is a novel inflammation biomarker with its higher levels involved in cardiometabolic diseases development. Taking into consideration that obesity is an independent risk factor for many cardiometabolic diseases, we aimed to explore the relationship between endocan levels and novel anthropometric indices [i.e., body adiposity index (BAI), cardiometabolic index (CMI), a body shape index, body roundness index, conicity index, lipid accumulation product index and visceral adiposity index] and traditional ones [i.e., waist circumference, hip circumference, body mass index, waist-to-height ratio and waist-to-hip ratio] in adult population. METHODS: A total of 177 participants were included. Anthropometric indices and biochemical parametres were measured. RESULTS: Univariate regression analysis demonstrated positive correlations of endocan and almost all anthropometric data. To explore independent associations of endocan and anthropometric parameters, the Model which fulfilled criteria for ordinal regression testing was created. Adjusted odds for BAI given in the Model (OR=1.120, 95% CI 1.036-1.212, P=0.004), demonstrated that a rise in BAI by 1 unit increased the probability of higher endocan concentration by 12%. As well, a rise in CMI for 1 unit, increased the probability for higher endocan levels for 2.6 times (OR=2.599, 95% CI 1.006-6.712, P=0.049). A total of 20.1% of variation in endocan levels could be explained by this Model. CONCLUSIONS: Non-traditional obesity indices, BAI and CMI independently correlated with higher serum endocan levels in adult population.

A novel mechanism of vitamin D anti-inflammatory/antioxidative potential in type 2 diabetic patients on metformin therapy.

INTRODUCTION: The performed study focused on determining the effect of vitamin D supplementation on enzymes involved in both inflammation and reactive oxygen species (ROS) production and ROS degradation in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: The 6-month follow-up, randomized, controlled study included 140 patients with T2DM, ≥ 30 years old, with good metabolic control, treated with metformin and lifestyle advice only. All patients were randomly assigned to two groups (70 each). Patients from the first group (Intervention group) were assigned to receive vitamin D3 50 000 IU or 14 000 IU regarding their vitamin D baseline levels. Patients from the second (Metformin) group continued to receive only metformin during the 6-month study period. RESULTS: After 6 months, the myeloperoxidase activity was significantly lower and gradually decreased in the Intervention group by about 40%, compared to the baseline measurement (p = 0.015) and compared to the Metformin group (p = 0.001). After 6 months, the xanthine oxidase (XO) activity decreased significantly in the Intervention group compared to the baseline and 3rd month levels (p < 0.001). In the Metformin group there was also a significant decrease in XO after 6 months compared to baseline (p < 0.001) and the 3rd month (p = 0.003). The catalase activity significantly increased within the Intervention group only when comparing the 3rd and 6th month (p = 0.027). CONCLUSIONS: Our study showed that vitamin D may improve endothelial dysfunction in patients with T2DM on metformin therapy by influencing two important factors implicated in the pathogenesis of diabetic complications - ROS production and inflammation, which can additionally contribute to a stable metabolic control during metformin therapy.

Is endocan a novel potential biomarker of liver steatosis and fibrosis?

BACKGROUND: Studies that evaluated endocan levels in nonalcoholic fatty liver disease (NAFLD) and liver fibrosis are scarce. We aimed to explore endocan levels in relation to different stages of liver diseases, such as NAFLD, as determined with fatty liver index (FLI) and liver fibrosis, as assessed with BARD score. METHODS: A total of 147 participants with FLI≥60 were compared with 64 participants with FLI <30. An FLI score was calculated using waist circumference, body mass index, gamma-glutamyl transferase and triglycerides. Patients with FLI≥60 were further divided into those with no/mild fibrosis (BARD score 0-1 point; n=23) and advanced fibrosis (BARD score 2-4 points; n=124). BARD score was calculated as follows: diabetes mellitus (1 point) + body mass index≥28 kg/m2 (1 point) + aspartate amino transferase/alanine aminotransferase ratio≥0.8 (2 points). RESULTS: Endocan was independent predictor for FLI and BARD score, both in univariate [OR=1.255 (95% CI= 1.104-1.426), P=0.001; OR=1.208 (95% CI=1.029-1.419), P=0.021, respectively] and multivariate binary logistic regression analysis [OR=1.287 (95% CI=1.055-1.570), P=0.013; OR=1.226 (95% CI=1.022-1.470), P=0.028, respectively]. Endocan as a single predictor showed poor discriminatory capability for steatosis/fibrosis [AUC=0.648; (95% CI=0.568-0.727), P=0.002; AUC= 0.667 (95% CI=0.555-0.778), P=0.013, respectively], whereas in a Model, endocan showed an excellent clinical accuracy [AUC=0.930; (95% CI=0.886-0.975), P<0.001, AUC=0.840 (95% CI=0.763-0.918), P<0.001, respectively]. CONCLUSIONS: Endocan independently correlated with both FLI and BARD score. However, when tested in models (with other biomarkers), endocan showed better discriminatory ability for liver steatosis/fibrosis, instead of its usage as a single biomarker.

Endocan and a novel score for dyslipidemia, oxidative stress and inflammation (DOI score) are independently correlated with glycated hemoglobin (HbA1c) in patients with prediabetes and type 2 diabetes.

INTRODUCTION: We aimed to examine serum endocan level and the summary involvement of dyslipidemia, oxidative stress (OS) and inflammation by calculation of its comprehensive score (i.e. Dyslipidemia-Oxy-Inflammation (DOI) score) in relation to glucoregulation in subjects with prediabetes and overt type 2 diabetes (T2D). MATERIAL AND METHODS: A total of 59 patients with prediabetes and 102 patients with T2D were compared with 117 diabetes-free controls. Glycated hemoglobin (HbA1c), inflammation, OS and lipid parameters were measured. Associations of clinical data with HbA1c level were tested with univariate and multivariate logistic ordinal regression analysis. HbA1c as a dependent variable is given at the ordinal level (i.e. < 5.7%; 5.7-6.4%, > 6.4%, respectively). RESULTS: Endocan was significantly higher in the T2D group than in the controls. As endocan concentration rose by 1 unit, the probability for higher HbA1c concentration increased by more than 3 times (OR = 3.69, 95% CI: 1.84-7.01, p < 0.001). Also, a rise in the dyslipidemia score, oxy score, inflammation score and DOI score by 1 unit increased the probability of higher HbA1c concentration by 19%, 13%, 51% and 11%, respectively. In the models, after adjustment for confounding variables, endocan and DOI score remained independent predictors of HbA1c level. CONCLUSIONS: Endocan and DOI score are independently correlated with HbA1c in patients with prediabetes and overt T2D.

Predictive Values of Serum Uric Acid and Alanine-aminotransferase for Fatty Liver Index in Montenegrin Population.

BACKGROUND: Alanine-aminotransferase (ALT) and uric acid cut-off levels used in non-alcoholic fatty liver disease (NAFLD) diagnosis are advised to be lowered. Due to contradictory results on the utility of both these biomarkers for NAFLD screening, we aimed to determine their cut-off levels that can be applied to Montenegrin population with the fatty liver disease. METHODS: A total of 771 volunteers were enrolled. A fatty liver index (FLI) score ≥60 was used as proxy of NAFLD. The receiver operating characteristic curve analysis with the area under the curve (AUC) was used to determine the cut-off values of ALT and uric acid associated with FLI ≥60. RESULTS: ALT was independent predictor of FLI in both men and women, whereas serum uric acid was its independent predictor only in women. Lower cut-off levels of ALT are associated with the increased prevalence of NAFLD [i.e., ALT was 19 IU/L (AUC=0.746, sensitivity 63%, specificity 72%, P<0.001) in women and 22 IU/L (AUC=0.804, sensitivity 61%, specificity 95%, P<0.001) in men]. The cut-off value for uric acid was 274 µmol/L (AUC=0.821, sensitivity 68%, specificity 82%, P<0.001) in women. CONCLUSIONS: Lower cut-off levels of ALT in both genders, and serum uric acid in females, can be reliable predictors of the FLI.

Older age and HDL-cholesterol as independent predictors of liver fibrosis assessed by BARD score.

BACKGROUND: It is known that non-alcoholic fatty liver disease (NAFLD), and in particular non-alcoholic steatohepatitis, can progress to advanced fibrosis. However, pathophysiological mechanisms implicated in this evolution are not elucidated yet. We aimed to investigate the independent predictors of liver fibrosis in patients with NAFLD, determined by BARD score, one of the most used algorithms for fibrosis evaluation. METHODS: This prospective study enrolled a total of 301 participants with NAFLD, as determined by a Fatty Liver Index (FLI) ≥60. All patients were categorized into two groups: with no/mild fibrosis (BARD score 1, N.=62) and with advanced fibrosis (BARD score 2, 3 and 4 N.=239). RESULTS: Serum high density lipoprotein cholesterol (HDL-c), glucose and glycated hemoglobin were higher (P=0.028, P<0.001 and P=0.002, respectively), whereas serum transaminases and gamma glutamil transferase levels were lower in patients with advanced fibrosis than in those with no/mild fibrosis (P=0.010, P<0.001 and P=0.005, respectively). There were no significant differences in oxidative stress (i.e., advanced oxidant protein products and malondialdehyde) and anti-oxidative protection markers (i.e., catalase) between patients with no/mild fibrosis and advanced fibrosis. Multivariate ordinal regression analysis showed independent associations and predictions of ages (OR=1.071, 95% CI 1.004-1.097, P<0.001), and HDL-c levels (OR=2.549, 95% CI 1.087-5.989, P=0.032) on BARD score categories in patients with NAFLD. CONCLUSIONS: In conclusion, we found that older age and higher HDL-c, are independent predictors for advanced liver fibrosis assessed with the BARD score. Future investigations are needed to further explore this relationship.

Nitric Oxide Products are not Associated with Metabolic Syndrome.

BACKGROUND: Nitric oxide (NO) is oxidative stress biomarker which is regarded as one of the key determinants of energy metabolism and vascular tone. Considering the controversial reports on the association between nitric oxide products (NOx) and metabolic syndrome (MetS), the aim of the current study was to examine that potential relationship. Additionally, we aimed to evaluate a broad spectrum of other oxidative stress biomarkers [i.e., malondialdehyde (MDA), advanced oxidation protein products (AOPP), xanthine oxidoreductase (XOD), xanthine oxidase (XO) xanthine dehydrogenase (XDH)] in relation with MetS. METHODS: A total of 109 volunteers (46.8% of them with MetS) were included in this cross-sectional study. Biohemical and anthropometric parameters, as well as blood pressure, were obtained. The MetS was diagnosed according to the International Diabetes Federation criteria. RESULTS: Multivariate logistic regression analysis showed that XOD (OR=1.011; 95% CI 1.002-1.019; p=0.016), XO (OR=1.014; 95% CI 1.003-1.026; p=0.016), MDA (OR=1.113; 95% CI 1.038-1.192; p=0.003) and AOPP (OR=1.022; 95% CI 1.005-1.039; p=0.012) were the independent predictors of MetS, whereas no association between NOx and MetS was found. As XOD rose for 1 U/L, XO for 1 U/L, MDA for 1 µmol/L and AOPP for 1 T/L, probability for MetS rose for 1.1%, 1.4%, 11.3% and 2.2%, respectively. Adjusted R2 for the Model was 0.531, which means that 53.1% of variation in MetS could be explained with this Model. CONCLUSION: Unlike XOD, MDA and AOPP, NOx is not associated with MetS.