Performance Evaluation of a Novel Non-Invasive Test for the Detection of Advanced Liver Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) may progress to advanced liver fibrosis (ALF). We evaluated the diagnostic accuracy of a novel Liver Fibrosis Risk Index (LFRI) in MAFLD subjects using transient elastography (TE) as the reference method for liver fibrosis measurement and then the diagnostic performance of a new two-step non-invasive algorithm for the detection of ALF risk in MAFLD, using Fibrosis-4 (FIB-4) followed by LFRI and comparing it to the reference algorithm based on FIB-4 and TE. We conducted a prospective study on 104 MAFLD European adult subjects. All consenting subjects underwent TE and measurements of FIB-4 and LFRI. For FIB-4 and TE, validated cut-offs were used. An ROC analysis showed that LFRI diagnosed severe fibrosis with moderate accuracy in MAFLD subjects with a negative predictive value above 90%. Using the new algorithm with LFRI thresholds recommended by the manufacturer, the number of subjects classified into ALF risk groups (low, intermediate, or high) differed significantly when compared with the reference algorithm (p = 0.001), with moderate agreement between them (weighted kappa (95% CI) = 0.59 (0.41-0.77)). To improve the performance of the LFRI-based algorithm, we modified cut-off points based on ROC curves obtained by dividing the study population according to the reference algorithm and observed no difference between algorithms (p = 0.054) in categorizing ALF risk, with a slight increase in the total agreement (weighted kappa (95% CI) = 0.63 (0.44-0.82)). Our findings suggest that using the novel LFRI as a second-line test may represent a potential alternative for liver fibrosis risk stratification in MAFLD patients; however, modified cut-offs are needed to optimize its performance.

Reference values and biological determinants for cardiac myosin-binding protein C concentrations assessed with an enzyme-linked immunosorbent assay.

Background: Cardiac myosin-binding protein C (cMyC) is a novel cardio-specific biomarker of potential diagnostic and prognostic value for cardiovascular events. This study aims to determine reference values for cMyC and identify biological determinants of its concentration. Methods: A population of 488 presumably healthy adults were enrolled to define biological determinants which affect cMyC concentrations in serum. Concentrations of cMyC were assessed using enzyme-linked immunosorbent assays from commercially available kits. Eligibility for inclusion in this study evaluated all subjects' anthropometric, demographic and laboratory measurements. After applying strict inclusion criteria, a reference population (n=150) was defined and used to determine reference values. Reference values were derived using a robust method.

Diagnostic Performance of Biomarker-Based Scores as Predictors of Metabolic Dysfunction-Associated Fatty Liver Disease Risk in Healthy Children.

INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MAFLD)-a new definition for non-alcoholic fatty liver disease-reflects the impact of metabolic abnormalities on liver function. We assessed the diagnostic accuracy of biomarker-based scores for prediction of MAFLD in apparently healthy children. METHODS: This study included 144 children aged 9-11. MAFLD was recognized in 14 girls and 29 boys. Anthropometric indices, glycemia, insulin resistance, lipid profile, enzymes (ALT, AST, GGT, ALP), CRP, N-terminal propeptide of type I procollagen (P1NP) and collagen type I C-telopeptide (CTX-1) levels were measured. Fatty liver and hepatic steatosis index (FLI, HSI) and potential indicators of liver fibrogenesis: P1NP/ALP, P1NP/ALPxALT, P1NP/ALPxCRP were calculated. RESULTS: P1NP/ALPxALT and P1NP/ALPxCRP were significantly higher in subjects with MAFLD. FLI was a good, significant predictor of MAFLD occurrence, regardless of sex. In boys, P1NP/ALPxCRP was a comparable predictor as CRP (OR 1.14 vs. 1.17; p < 0.001). P1NP/ALPxCRP had better discrimination capability in boys (AUC = 0.79; p < 0.001). However, the use of this algorithm did not improve discriminatory power in comparison to CRP (AUC = 0.81; p < 0.001), but gave a better sensitivity for MAFLD prediction (86% vs. 59%). CONCLUSIONS: We suggest that P1NP/ALPXCRP is a reliable tool for MAFLD prediction in routine pediatric practice.

Discordance between lipoprotein (a) and LDL-cholesterol levels in cardiovascular risk assessment in apparently healthy subjects.

BACKGROUND AND AIMS: Lipoprotein(a) is a recognized independent cardiovascular risk factor and apolipoprotein B (apoB) level better reflects the risk than LDL-cholesterol. Despite this cardiovascular prediction mostly relies on traditional risk factors. We evaluated the association between Lp(a) and lipid biomarkers of cardiovascular risk in relation to age and sex in apparently healthy individuals. METHODS AND RESULTS: 422 presumably healthy subjects aged 19-84 were included. Lipid profile, Lp(a), apoB and small dense low-density lipoprotein cholesterol (sdLDL-C) were assayed. Subjects were divided at desirable cut-points of apoB and LDL-C. A group with elevated apoB (≥100 mg/dL) at low LDL-C (≤115 mg/dL) was appointed as high-risk and a group with low apoB but elevated LDL-C as low-risk. Significantly elevated triglycerides, TG/HDL-C and sdLDL-C were found in high risk group, but Lp(a) levels were comparable. TG/HDL-C was the best predictor of high risk with a very good diagnostic accuracy (AUC = 0.85), whereas Lp(a) had no discriminatory power. Women aged ≤40 with low LDL-C ≤ 100 mg/dL and elevated Lp(a) ≥ 40 mg/dL had higher levels of apoB and sdLDL-C (p = 0.002; p = 0.07) than those with Lp(a) < 40 mg/dL, which was not observed in men. In young females increase of LDL-C and apoB significantly raised the risk of elevated Lp(a). CONCLUSIONS: Women younger than 40 with low LDL-C may be at increased cardiovascular risk associated with elevated Lp(a) and apolipoprotein B levels. Inclusion of Lp(a) and apoB in the routine lipid testing providing information on an individual level may improve the prediction of cardiovascular risk in primary prevention.

Determinants of Lipid Parameters in Patients without Diagnosed Cardiovascular Disease-Results of the Polish Arm of the EUROASPIRE V Survey.

To assess the determinants of lipid parameters in primary care patients without diagnosed cardiovascular disease (CVD), a cross-sectional study was conducted during 2018-2019 with a total of 200 patients. The following lipid parameters were measured: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), small, dense LDL (sdLDL-C), and lipoprotein (a) (Lp(a)). Predictors of elevated and adequately controlled lipid parameters were assessed with logistic regression analysis. Older age was related to higher risk of TC ≥ 6.2 mmol/L [OR 1.03 (95% CI 1.0-1.05)], sdLDL-C ≥ 1.0 mmol/L [OR 1.05 (95% CI 1.0-1.1)], and decreased risk of Lp(a) ≥ 50 mg/dL [OR 0.97 (95% CI 0.94-0.99)]. Patients with diabetes mellitus (DM) had increased probability of TG ≥ 2.25 mmol/L [OR 3.77 (95% CI 1.34-10.6)] and Lp(a) ≥ 50 mg/dL [OR 2.97 (1.34-6.10)] as well as adequate control of TG and Lp(a). Higher material status was related to lower risk of TC ≥ 6.2 mmol/L [OR 0.19 (95% CI 0.04-0.82)] and LDL-C ≥ 3.6 mmol/L [OR 0.33 (95% CI 0.12-0.92)]. High BMI was related to increased [OR 1.14 (95% CI 1.02-1.29)], and female gender [OR 0.33 (95% CI 0.12-0.96)] and hypertension [OR 0.29 (95% CI 0.1-0.87)] to decreased risk of TG ≥ 2.25 mmol/L [OR 1.14 (95% CI 1.02-1.29)]. Taking lipid-lowering drugs (LLD) was associated with LDL-C < 2.6 mmol/L [OR 2.1 (95% CI 1.05-4.19)] and Lp(a) < 30 mg/dL [OR 0.48 (95% CI 0.25-0.93)]. Physical activity was related to LDL-C < 2.6 mmol/L [OR 2.02 (95% CI 1.02-3.98)]. Higher abdominal circumference was associated with decreased risk of TG < 1.7 mmol/L [OR 0.96 (95% CI 0.93-0.99)]. Elevated lipid parameters were related to age, gender, material status, BMI, history of DM, and hypertension. Adequate control was associated with age, education, physical activity, LLD, history of DM, and abdominal circumference.

Association between Fasting and Postprandial Levels of Liver Enzymes with Metabolic Syndrome and Suspected Prediabetes in Prepubertal Children.

Elevated liver enzyme activity may be associated with metabolic syndrome (MetS); however, it is not included in the MetS definition for children. Postprandial changes in the levels of biochemistry tests are related to manifestations of metabolic abnormalities. We assessed the association between fasting and postprandial liver enzymes levels with MetS and elevated hemoglobin A1c (HbA1c) in children aged 9-11. The study included 51 girls and 48 boys, all presumably healthy. In all participants' anthropometric indices, fasting glucose, insulin, lipid profile and HbA1c were measured. Enzymes, including alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), were assayed in fasting and postprandial states. Individuals were divided into subgroups: with (MetS(+): n = 26); without MetS (MetS(-): n = 73); with HbA1c levels ≤ 5.3% (n = 39); and ≥5.7% (n = 11). Elevated fasting GGT levels were found in 23% of MetS(+) children and rarely in MetS(-) children; increased postprandial GGT was noted in 35% of MetS(+) individuals. Postprandial GGT changes tend to predict MetS (OR = 1.16; p = 0.092). Increased fasting ALT was found rarely in MetS(+) children, but did not occur in MetS(-) children. HbA1c ≥ 5.7% occurred rarely and neither fasting ALT nor GGT were related to elevated HbA1c. However, postprandial change of ALT was a good positive predictor of increased HbA1c (OR = 1.33; p = 0.021). Postprandial GGT performs better as an indicator of metabolic syndrome occurrence, and instead postprandial ALT may predict prediabetes in prepubertal children.

Serum ANGPTL8 and ANGPTL3 as Predictors of Triglyceride Elevation in Adult Women.

Angiopoietin-like proteins ANGPTL3 and ANGPTL8 have been shown to inhibit lipoprotein lipase, and thus regulate triglyceride level in the circulation. Whether the regulation of lipid metabolism by ANGPTLs is affected by the menopausal status remains unclear. We aimed to assess the relationships between serum ANGPTL3 and ANGPTL8 and atherogenic biomarkers in presumably healthy women during ageing. The study group included 94 women of whom 31 were premenopausal (PRE ≤ 40 years) and 37 were postmenopausal (POST ≥ 52 years). Atherogenic lipid and non-lipid biomarkers and ANGPTLs (ANGPTL3, ANGPTL8) were assayed in serum samples. TG/HDL-C index, non-HDL-cholesterol, remnant cholesterol concentrations, and BMI were calculated. Median levels of ANGPTL3 and concentrations of lipid biomarkers were significantly higher in POST comparing to PRE but ANGPTL8 levels were not different. In PRE, ANGPTL8 levels correlated significantly with TG and TG/HDL-C index while there were no correlations between ANGPTL3 and these biomarkers. In POST both ANGPTLs correlated with TG, sdLDL-C, and TG/HDL-C. ANGPTL8 and sd-LDL-C were the most significant predictors of early triglyceride elevation > 100 mg/dL (1.13 mmol/L) in the whole group and POST whereas the prediction power of ANGPTL3 was negligible in the whole group and non-significant in the subgroups. We demonstrated a significant positive correlation of ANGPTL3 with age category which predisposes to postmenopause. Despite the increase in ANGPTL3 level with ageing the ANGPTL3/ANGPL8 ratio was maintained. In conclusion, ANGPTL8 predicts the early triglyceride elevation better than ANGPTL3, especially in postmenopausal women. The association of ANGPTL3 with triglyceride levels is weaker than ANGPTL8 and depends on menopausal status. We suggest that the choice for the best efficient treatment of dyslipidemia with new inhibitors of angiopoietin-like proteins may depend on the menopausal status.

Relationships between Bone Turnover Markers and Factors Associated with Metabolic Syndrome in Prepubertal Girls and Boys.

The associations between individual components of metabolic syndrome (MetS) and bone health in children are complex, and data on this topic are sparse and inconsistent. We assessed the relationship between bone turnover markers and markers of the processes underlying MetS (insulin resistance and inflammation) in a group of presumably healthy children aged 9-11 years: 89 (51 girls, 38 boys) presenting without any features of MetS and 26 (10 girls, 16 boys) with central obesity and two features of MetS. Concentrations of glucose, triglycerides (TG), HDL cholesterol (HDL-C), C-reactive protein (CRP), HbA1c, total 25-hydroxyvitamin D (25(OH)D), intact-P1NP (N-terminal propeptide of type I procollagen), CTX-1 (C-terminal telopeptide of type I collagen) were assayed and insulin resistance was assessed (HOMA-IR). BMI centile, waist circumference (WC) and blood pressure were measured. The presence of MetS in girls resulted in significantly lower concentrations of CTX-1 and a trend to lower CTX-1 in boys. The concentrations of bone formation marker i-P1NP were not affected. Among the features associated with MetS, HOMA-IR appeared as the best positive predictor of MetS in girls, whereas CRP was the best positive predictor in boys. A significant influence of HOMA-IR on the decrease in CTX-1 in girls was independent of BMI centile and WC, and the OR of having CTX-1 below the median was 2.8-fold higher/1SD increased in HOMA-IR (p = 0.003). A weak relationship between CTX-1 and CRP was demonstrated in girls (r = -0.233; p = 0.070). Although TG, as a MetS component, was the best significant predictor of MetS in both sexes, there were no correlations between bone markers and TG. We suggest that dyslipidemia is not associated with the levels of bone markers in prepubertal children whereas CRP is weakly related to bone resorption in girls. In prepubertal girls, insulin resistance exerts a dominant negative impact on bone resorption, independent of BMI centile and waist circumference.

Practice in financial support of third party organised conferences and courses at a national level for health care professionals in Europe.

Background Ethical MedTech prescribes high standards for the participation of the in vitro diagnostics (IVD) industry in third-party organised educational events in terms of charitable donations, educational grants, scholarships and fellowships. We planned a survey to investigate the previous and current practice in terms of cooperation between professionals or professional societies and the IVD industry, as well as plans under the incorporation of the MedTech Europe Code. Methods Different questions, from general information to specific questions related to the practice and knowledge of the new Ethical MedTech Code, were included in two different surveys; for European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) National Societies' (NSs) representatives, and for their (NSs) individual members. Results Twenty-five out of 40 EFLM NS representatives replied; more than half declared that all different types of financial resources were available for supporting the continuing professional education of health care professionals (HCPs). In addition, 322 individual responses collected from 31 NSs, answered that the institutional director (50.3%) or laboratory chief (70.1%) made generally made a decision, without specific criteria. Conclusions The MedTech Europe Code is already adopted or is about to be adopted in numerous EFLM NSs, but most of them have not implemented it as yet. The use of the Code and better communication between IVD companies and HCPs are necessary to guarantee an improved and fair use of financial support, as well as better choices for the organisation and attendance at scientific events.

Association between Fasting Glucose Concentration, Lipid Profile and 25(OH)D Status in Children Aged 9⁻11.

BACKGROUND: The aim of this study was to assess the relationship between vitamin D status and the prevalence of dyslipidemia and impaired fasting glucose (IFG) in children. Methods and Summary: 284 children (150 boys and 134 girls) aged 9⁻11 were included in the study. Children with deficient 25(OH)D (25-hydroxycholecalciferol) levels ≤20 ng/mL (50 nmol/L) were characterized by a more frequent occurrence of impaired fasting glucose (IFG) (Odd ratios (OR) = 1.966, 95% confidence interval (CI): 1.055⁻3.663; p = 0.033) when compared to children with 25(OH)D >20 ng/mL. Serum 25(OH)D with concentration lower by 1 ng/mL (2.5 nmol/L) was linked to higher fasting glucose (by 0.25 mg/dL, 0.013 mmol/L; p = 0.017), higher total cholesterol (TC) by almost 1 mg/dL (0.96 mg/dL, 0.25 mmol/L; p = 0.006) and higher high-density lipoprotein cholesterol (HDL-C) (by 0.57 mg/dL, 0.015 mmol/L; p < 0.001). CONCLUSION: 25(OH)D deficiency may negatively affect fasting glucose and total cholesterol concentration in children aged 9⁻11. Vitamin D-deficient children are twice as likely to develop prediabetes as reflected by impaired fasting glucose when compared to those with a 25(OH)D level above 20 ng/mL (50 nmol/L).

Non-fasting lipid profile determination in presumably healthy children: Impact on the assessment of lipid abnormalities.

OBJECTIVE: Despite the common use of non-fasting measurements for lipid profile in children it remains unclear as to the extent non-fasting conditions have on laboratory results of lipids measurements. We aimed to assess the impact of non-fasting lipid profile on the occurrence of dyslipidemia in children. MATERIALS AND METHODS: Basic lipid profile including: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), as well as small, dense-LDL-C (sd-LDL-C), apolipoprotein AI (ApoAI), apolipoprotein B (ApoB) and lipoprotein(a) [Lp(a)], were measured in 289 presumably healthy children aged 9-11 in both fasting and non-fasting condition. The clinical impact of non-fasting lipid profile was evaluated individually for each child with estimation of false positive (FP) and false negative (FN) results. RESULTS: The highest percentage of FP results in non-fasting condition was observed for TG (42.3%) being significantly higher when compared to FN results (p = 0.003). In contrast, the highest percentage of FN results in a non-fasting state were shown for LDL-C (14.3%), but the difference was statistically insignificant when compared to FP results. When comparing fasting and non-fasting lipid profile a number of significant differences was shown for: TG (p<0.001), HDL-C (p = 0.002) LDL-C (p<0.001) and ApoAI (p<0.001), respectively. The occurrence of dyslipidemia, recognized on the basis of non-fasting lipids was significantly higher (p = 0.010) when compared to fasting lipid profile. CONCLUSIONS: A higher occurrence of dyslipidemia, based on the measurement of non-fasting lipids in children, is suggestive of possible disorders in lipid metabolism. However, accurate identification of dyslipidemia by assessment of non-fasting lipids requires the establishment of appropriate cut-off values for children.

25-Hydroxyvitamin D, biomarkers of eosinophilic inflammation, and airway remodeling in children with newly diagnosed untreated asthma.

BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) and asthma development may be related to airway remodeling and eosinophilia. Periostin is proposed as a key molecule that links remodeling and eosinophilic inflammation. OBJECTIVE: We evaluated the association of 25(OH)D concentration with periostin, peripheral blood eosinophil counts, and immunoglobulin E (IgE) in children with newly diagnosed asthma. METHODS: The study included 150 children: 110 with atopic asthma and 40 constituted a reference group. Fasting blood was collected for cell counts and serum for measurements of 25(OH)D, periostin, IgE, and C-reactive protein (CRP) concentrations. RESULTS: Significantly lower 25(OH)D, elevated IgE concentrations, and eosinophil counts were found in children with asthma compared with the reference group (p = 0.0001). A lower forced expiratory volume in the first second of expiration percentage predicted value was associated with a lower 25(OH)D value in children with asthma. The bronchodilator reversibility was inversely related to serum 25(OH)D concentrations (R = -0.45, p = 0.029). The children with asthma and with a 25(OH)D deficient concentration (≤20 ng/mL) had higher concentrations of periostin (p = 0.035) and CRP (p = 0.01) than those with a sufficient 25(OH)D concentration (≥30 ng/L). Additional analysis revealed statistically significant differences (p = 0.013) when comparing periostin concentrations between subjects with a 25(OH)D deficient concentration (≤20 ng/mL) and subjects who did not have a deficient concentration (>20 ng/mL). In individuals with asthma, a 25(OH)D concentration of <30 ng/mL had no impact on eosinophilia, whereas IgE concentrations were associated with increased eosinophils, and the effect of periostin on eosinophilia was small although significant. Multivariate regression, including 25(OH)D concentration, CRP level, eosinophil counts, and sex, accounted for 7% of periostin variation in subjects with asthma. CONCLUSION: In newly diagnosed pediatric asthma, 25(OH)D concentrations revealed a small although significant association with periostin levels but no effect on eosinophilia. A low vitamin D concentration may increase airway remodeling induced by inflammatory mediators, but further clinical studies aimed to explain the causal link between vitamin D insufficiency and asthma are needed.

The influence of sample freezing at - 80 °C for 2-12 weeks on glycated haemoglobin (HbA1c) concentration assayed by HPLC method on Bio-Rad D-10® auto analyzer.

INTRODUCTION: The aim of the study was to evaluate the effect of a single freeze/thaw cycle on HbA1c concentrations measured by commercially available HPLC method. MATERIALS AND METHODS: Study included 128 whole blood samples collected from diabetic patients (N = 60) and healthy volunteers (N = 68). HbA1c concentrations were measured in fresh blood samples. Then samples were frozen at - 80 °C for up to 12 weeks. HbA1c was assayed by ion-exchange HPLC method on Bio-Rad D-10® analyzer. Variables were compared using Wilcoxon and ANOVA Kruskal-Wallis tests. Bias between HbA1c measured in fresh and frozen samples was calculated. The comparability of HbA1c concentrations was assessed by Bland-Altman plot. RESULTS: Median (IQR) HbA1c concentration was 45.3 (36.6-61.2) mmol/mol for fresh and 45.3 (36.6-60.6) mmol/mol for frozen/thawed samples. No significant difference in HbA1c concentrations was found comparing fresh and frozen/thawed samples (P = 0.070) in the whole group, as well as in healthy and diabetic subjects. The median calculated bias between fresh and frozen/thawed samples was 0% in whole group and healthy subjects, and 1.19% in diabetic patients. No significant difference was found between the biases according to baseline HbA1c values (P = 0.150). The Bland-Altman plot analysis showed a positive bias of 0.4% (95% CI: - 2.8 - 3.7%), which indicates high compliance between HbA1c values and no relevant influence of sample freezing on clinical significance of HbA1c measurement. CONCLUSIONS: Storage for up to 12 weeks at - 80 °C with a single freeze/thaw cycle does not affect HbA1c concentrations measured with HPLC method on Bio-Rad D-10® analyzer.

Metabolic Syndrome and Menopause: Pathophysiology, Clinical and Diagnostic Significance.

Menopause is a risk factor for cardiometabolic diseases, including metabolic syndrome (MetS), type 2 diabetes, and cardiovascular diseases. MetS is a constellation of interdependent factors such as insulin resistance, abdominal obesity, dyslipidemia, and hypertension. The prevalence of MetS in postmenopause is due to loss of the protective role of estrogens and increased circulating androgens resulting in changes to body fat distribution and development of abdominal obesity. Excessive visceral adipose tissue plays an important role due to synthesis and secretion of bioactive substances such as adipocytokines, proinflammatory cytokines, reactive oxygen species, prothrombotic, and vasoconstrictor factors. MetS may also impact risk assessment of breast cancer, osteoporosis and chronic kidney disease, and quality of life during the menopausal transition. Increased MetS has stimulated the exploration of new laboratory tests for early detection and therapies.

Secreted frizzled-related protein 4 (SFRP4) and fractalkine (CX3CL1) - Potential new biomarkers for ß-cell dysfunction and diabetes.

The discovery of new risk factors for diabetes is a major challenge for contemporary science. Pathogenesis of type 2 diabetes mellitus (T2DM) is closely related to adipose tissue dysfunction. The aim of this review was to describe recently discovered cytokines: fractalkine (CX3CL1, FKN) and secreted frizzled-related protein 4 (SFRP4) as potential biomarkers of early ß cell dysfunction and diabetes. The association of CX3CL1 and SFRP4 with low-grade inflammation in adipose tissue links obesity with disturbances in insulin secretion and impaired glucose metabolism, therefore it indicates new therapeutic and preventive targets in both healthy and diabetic subjects.

Diabetes as a complication of adipose tissue dysfunction. Is there a role for potential new biomarkers?

Increasing incidence of type 2 diabetes is a major health problem of the modern world and requires new diagnostic tools to assess early metabolic disorders, particularly insulin resistance. The link between obesity, inflammation and insulin resistance indicates the important secretory role of adipose tissue. Proinflammatory factors (cytokines, adipokines) produced by enlarged adipose tissue are related to impaired glucose metabolism. Adipokines act as paracrine factors in adipose tissue and as endocrine hormones in the liver, muscles and central nervous system. Novel adipokines secreted from adipocytes such as retinol binding protein-4 (RBP-4), vaspin, omentin, chemerin, fibroblast growth factor 21 (FGF21), adipocyte fatty acid-binding protein (A-FABP) and dipeptidyl peptidase 4 (DPP4) demonstrate pleiotropic activity and their insulin-sensitizing or enhancing insulin resistance properties have not been clearly confirmed yet. In spite of the lack of standardized automated assay methods currently available for these novel biomarkers, promising results from several studies emphasize that they might potentially be useful prognostic factors for diabetes and its complications, especially in individuals without the typical symptoms of metabolic syndrome.

Comparison of Apolipoprotein Concentrations and Values of APOB:APOAI with Traditional Lipid Measures in Women Diagnosed with Acute Cornonary Syndromes - A Preliminary Report.

BACKGROUND: Acute coronary syndromes (ACS) are the leading cause of hospitalization and death in the modern world. Reliable indicators of risk assessment could be useful in clinical investigation. Results from recent studies suggest that apolipoprotein measurement and apoB:apoI ratio are superior to traditional lipids in the estimation of coronary risk. We compared apolipoprotein concentrations and apoB:apoAI index with traditional lipid measures in ACS patients. METHODS: A study group consisted of 94 women diagnosed with ACS (STEMI=21, NSTEMI=25 and UA=48). Clinically healthy volunteers (n=30) served as controls. Measurements of serum cardiac TnI, lipid profile, high sensitivity C-reactive protein, apolipoprotein AI and apoB100 concentrations were performed and apoB:apoAI ratio was calculated. RESULTS: ACS patients had significantly decreased median HDL-cholesterol, increased atherogenic indexes TC:HDL-C, apoB:apoAI and abnormally high CRP compared to controls. Median LDL-cholesterol and apoAI concentrations, although significantly higher in ACS patients, remained within the normal range. Comparison of atherogenic indexes in ACS patients has shown increased TC:HDL-C (>4) and apoB:apoAI (>0,3) in 60,4% and 96,8% of which 55,4% had moderate and high risk (>0,6). ApoB:apoAI ratio was of good diagnostic utility for discrimination between ACS cases and non-ACS controls (AUC=0,715), and little better than TC:HDL-C. In both groups similar percentage of increased LDL-C and triglycerides was observed whereas increased apoB concentration was three times more likely in ACS cases. The highest apoB:apoAI was observed predominantly in STEMI cases (49%) whereas the lowest in UA and NSTEMI (30%). CONCLUSIONS: Determination of apolipoproteins and assessment of apoB:apoAI ratio seems to be useful and better tool than traditional lipid measures in assessing risk of acute coronary syndromes in women.

Association Between Vitamin D Deficiency and Allergic Diseases.

Vitamin D is important for the regulation of bone and muscle metabolism and other functions in the human body. The hydroxylated forms of vitamin D2 and D3 are the most important, however only 1,25(OH)D2 is a fully active product. This hormone exert its pleiotropic actions via the specific receptor VDR, an important transcription factor. The optimal vitamin D concentration in the blood is >20 ng/mL whereas insufficiency and deficiency are 10-20 ng/mL and <10 ng/mL, respectively. To maintain the optimal vitamin D status the total vitamin D intake in children should be at least 400 IU/day. Several studies have shown the effects of vitamin D on proinflammatory cytokines, regulatory T cells and immune response. Vitamin D is a very important activator of the immune response, and in hypovitaminosis D, T killer cells are not able to fight off serious infections. A negative correlation between IgE and vitamin D concentration and a positive relation between vitamin D and lung function was documented in children and teenagers with asthma. In asthmatic children the vitamin D deficiency is associated with a higher corticosteroid use. Vitamin D supplementation in patients with steroid resistant asthma can potentially increase the glucocorticoid therapeutic response. Recently, a new mediator in allergy pathogenesis was reported - IL-33 and its soluble receptor ST2. IL-33 promotes the Th2 lymphocytes response as well as the activation of both mast cells and eosinophils via the ST2 receptor.

Is there an association of allergy and cardiovascular disease?

Cardiovascular diseases and allergic diseases occur commonly in developed countries. They lead to serious health complications and significantly impair the quality of life. Both types of diseases are characterized by excessive inflammatory processes. Recent studies suggest a link between allergy and an increased risk of cardiovascular disease, resulting from overactivity of the immune system in allergic diseases and increased synthesis of proinflammatory mediators, which has been well documented in the pathogenesis of atherosclerosis. The aim of this article is to present current data on the role of proinflammatory factors in the pathogenesis of cardiovascular diseases and allergies and on potential relationship between these disorders.