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.

Relationship between Serum Angiopoietin-like Proteins 3 and 8 and Atherogenic Lipid Biomarkers in Non-Diabetic Adults Depends on Gender and Obesity.

Hypertriglyceridemia is an independent risk factor for coronary artery disease. Lipoprotein lipase (LPL) plays an essential role in the metabolism of triglyceride-rich lipoproteins (TRLs). Angiopoietin-like proteins ANGPTL3 and ANGPTL8 are shown to be important regulators of LPL activity. Increased concentrations of these proteins may reflect cardiovascular risk, and the treatment of patients with dyslipidemia with ANGPTLs inhibitors may decrease this risk. We assessed the gender-specific relationships of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and obesity in non-diabetic adults. The study comprised 238 participants aged 25-74 [122 with triglycerides (TG) <150 mg/dL (<1.7 mmol/L) and 116 with hypertriglyceridemia]. Total cholesterol, HDL-cholesterol, LDL-cholesterol, TG, C-reactive protein (CRP), glycated hemoglobin, apolipoprotein B, small dense LDL-C (sd-LDL-C), ANGPTL3, and ANGPTL8 were measured. Non-HDL-cholesterol, remnant cholesterol (remnant-C) concentrations, and body mass index (BMI) were calculated. Results: Women and men did not differ in terms of age, CRP levels, the percentage of obese subjects, and concentrations of atherogenic lipid biomarkers, except higher TG in males and higher ANGPTL3 concentrations in females. Positive correlations of both ANGPTLs with TG, remnant-C, and sdLDL-C levels were found in females. In males, only ANGPTL3 correlated positively with atherogenic biomarkers, but there were no correlations with ANGPTL8. Concentrations of ANGPTL3 were higher in obese men, whereas ANGPTL8 levels were higher in obese women. In women alone, ANGPTL8 showed very good discrimination power to identify subjects with hypertriglyceridemia (AUC = 0.83). Contrary to this, ANGPTL3 was a better discriminator of hypertriglyceridemia (AUC = 0.78) in male subjects. Regression models, adjusted for age, sex, and BMI showed a weak but significant effect of ANGPTL8 to increase the risk of hypertriglyceridemia. Conclusions: In females, ANGPTL8 is more strongly associated with TRLs metabolism, whereas in males, ANGPTL3 plays a more important role. We suggest sex differences be taken into consideration when applying new therapies with angiopoietin-like proteins inhibitors in the treatment of dyslipidemia.

Gonadotropins and Their Association with the Risk of Prediabetes and Type 2 Diabetes in Middle-Aged Postmenopausal Women.

Recent studies have suggested that a low concentration of follicle-stimulating hormone (FSH) is associated with a higher prevalence of metabolic disturbances in postmenopausal women. In this study, we aim to evaluate the association between FSH, luteinizing hormone (LH), and LH/FSH ratio values and the risk of insulin resistance (HOMA-IR >2.0), prediabetes (IFG), and type 2 diabetes in a 5-year prospective study in postmenopausal women. 114 postmenopausal women were divided into 4 groups: group 1 (baseline and follow-up normoglycemic women), group 2 (normoglycemic women at baseline progressing to IFG), group 3 (women with baseline and follow-up IFG), and group 4 (women with baseline IFG progressing to diabetes). Baseline and follow-up anthropometric measurements and blood collections were performed. Serum/plasma was assayed for glucose, HDL-C, TG, C-reactive protein (CRP), 17beta-estradiol, estrone, insulin, thyroid-stimulating hormone (TSH), FSH, and LH. Homeostatic model assessment of insulin resistance (HOMA-IR) and LH/FSH ratios were calculated. The baseline concentrations of FSH and LH statistically decreased across all four groups (the highest concentrations in group 1 and the lowest in group 4; p < 0.001). A logistic regression analysis showed that a 1 SD decrease in the z-score of FSH concentration is associated with a threefold increased risk of IFG and a fivefold increased risk of HOMA-IR of >2.0 and diabetes. The LH concentration had odds ratio (OR) values about two times lower than the FSH concentration. The ORs of the LH/FSH ratio were only significant for IFG. In conclusion, FSH concentration is strongly associated with insulin resistance, prediabetes, and diabetes in postmenopausal women with normal or impaired fasting glucose. LH and the LH/FSH ratio are also related to metabolic disturbances after menopause, yet to a lesser extent.

Activity of metalloproteinases and adiponectin in obese patients-a possible factor of incisional hernias after bariatric procedures.

PURPOSE: Metalloproteinases are a key component of the pathogenesis of abdominal hernias. Obesity is considered a risk factor in herniogenesis and hernia recurrence. The aim of this study was to evaluate the serum concentrations of metalloproteinase-2 (MMP-2), MMP-9, MMP-13, and adiponectin in morbidly obese and non-overweight controls. MATERIALS AND METHODS: The participants were recruited from among patients undergoing bariatric and non-bariatric surgery and divided into two groups: I (body mass index (BMI)≥35 kg/m2, n=40) and II (BMI<25 kg/m2, n=30). Serum concentrations of MMP-2, MMP-9, MMP-13, and adiponectin were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: A statistically significant difference between groups was observed for MMP-2 concentration. The median MMP-9 concentration was higher in the obese group, but the difference was not statistically significant. Median MMP-13 concentrations did not differ between groups. Serum adiponectin concentration was insignificantly higher in the non-obese group. CONCLUSIONS: The elevated serum MMP-2 and MMP-9 concentrations in obese individuals may be related to the higher incidence of incisional hernias in this population.

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.

Impact of lipid markers and high-sensitivity C-reactive protein on the value of the 99th percentile upper reference limit for high-sensitivity cardiac troponin I.

OBJECTIVES: i) To assess the relationship between lipid markers and high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity cardiac troponin I (hs-cTnI) in the reference population, and ii) to evaluate the impact of lipid markers and hs-CRP on the 99th percentile upper reference limit (URL) for hs-cTnI. METHODS: 531 questionnaire-identified presumably healthy individuals were enrolled in a single-center, cross-sectional study. Surrogate biomarkers for diabetes, myocardial and renal dysfunction were used to refine the healthy cohort (n=408). Lipid profile, total cholesterol:high-density lipoprotein cholesterol (HDL-C) ratio, non-HDL-C, apolipoprotein AI (apoAI), apolipoprotein B (apoB), apoB:apoAI ratio, lipoprotein(a), small dense low-density lipoprotein cholesterol (LDL-C) and hs-CRP were determined. RESULTS: Individuals with detectable vs. non-detectable hs-cTnI concentrations more often showed elevated LDL-C (60% vs. 46%; p=0.002), apoB (73% vs. 61%; p=0.008), apoB:apoAI ratio (53% vs. 40%; p=0.005) and lipoprotein(a) (15% vs. 7%; p=0.015). The apoB:apoAI ratio and to a lesser extent other lipid markers, but not hs-CRP, were positively associated with hs-cTnI concentration in univariate and multivariate analyses. Exclusion of individuals with elevated apoB:apoAI ratio or apoB, but not hs-CRP, lowered the 99th percentile URL in the healthy cohort respectively by 12.9% (6.2 vs. 5.4ng/L) and 14.5% (6.2 vs. 5.3ng/L). The corresponding reduction for both lipid biomarkers in the presumably healthy population was 24.0% (7.5 vs. 5.7ng/L). CONCLUSION: Our study demonstrates that atherogenic lipid markers, particularly apoB:apoAI ratio or apoB, influence the 99th percentile URL for hs-cTnI.

The employment of IVF techniques for establishment of sodium, copper and selenium impact upon human sperm quality.

We analysed sodium (Na), copper (Cu) and selenium (Se) levels in human semen and glutathione peroxidase activity (GPx) in seminal plasma and examined their relationships with sperm quality. Semen samples were obtained from men (n=168) undergoing routine infertility evaluation. The study design included two groups based on standard ejaculate parameters: Group I (n=39) with normal ejaculates (normozoospermia) and Group II (n=129) with a pathological spermiogram. Se concentration (but not Na or Cu) and GPx activity were significantly higher in normozoospermic males than in those with a pathological spermiogram and also in males with correct sperm motility and normal sperm morphology than in asthenozoospermic and teratozoospermic males. There were significant correlations between sperm motility, Se and GPx, between rapid progressive motility and Cu, between sperm motility and Na, between normal sperm morphology and Se and Cu and between sperm concentration and Cu and GPx. Significant correlations were found between Na and Cu, between Na and Se and between Cu and Se in human semen in relation to alcohol consumption and tobacco use. Na, Cu, Se and GPx are related to sperm characteristics and male fertility and their survey could improve male infertility diagnosis.

Do toxic heavy metals affect antioxidant defense mechanisms in humans?

The aim of this study was to prove whether anthropogenic pollution affects antioxidant defense mechanisms such as superoxide dismutase (SOD) and catalase (CAT) activity, ferritin (FRT) concentration and total antioxidant status (TAS) in human serum. The study area involves polluted and salted environment (Kujawy region; northern-middle Poland) and Tuchola Forestry (unpolluted control area). We investigated 79 blood samples of volunteers from polluted area and 82 from the control in 2008 and 2009. Lead, cadmium and iron concentrations were measured in whole blood by the ICP-MS method. SOD and CAT activities were measured in serum using SOD and CAT Assay Kits by the standardized colorimetric method. Serum TAS was measured spectrophotometrically by the modified Benzie and Strain (1996) method and FRT concentration-by the immunonefelometric method. Pb and Cd levels and SOD activity were higher in volunteers from polluted area as compared with those from the control (0.0236 mg l(-1) vs. 0.014 mg l(-1); 0.0008 mg l(-1) vs. 0.0005 mg l(-1); 0.137 Um l(-1) vs. 0.055 Um l(-1), respectively). Fe level, CAT activity and TAS were lower in serum of volunteers from polluted area (0.442 g l(-1) vs. 0.476 gl(-1); 3.336 nmol min(-1)ml(-1) vs. 6.017 nmol min(-1)ml(-1); 0.731 Trolox-equivalents vs. 0.936 Trolox-equivalents, respectively), whilst differences in FRT concentration were not significant (66.109 µg l(-1) vs. 37.667 µg l(-1), p=0.3972). Positive correlations between Pb (r=0.206), Cd (r=0.602) and SOD in the inhabitants of polluted area, and between Cd and SOD in the control (r=0.639) were shown. In volunteers from both studied environments TAS-FRT (polluted: r=0.625 vs. control: r=0.837) and Fe-FRT (polluted area: r=0.831 vs. control: r=0.407) correlations, and Pb-FRT (r=0.360) and Pb-TAS (r=0.283) in the control were stated. The higher lead and cadmium concentrations in blood cause an increase of SOD activity. It suggests that this is one of the defense mechanisms of an organism against oxidative stress caused by environmental factors, whilst non-enzymatic mechanisms marked by TAS are the main antioxidant defense system in relation with Pb concentration in humans from unpolluted area. Simultaneously, the higher CAT activity and TAS can indicate that these mechanisms play a key role in the antioxidant protection in non-stressed environments.

Zinc and iron concentration and SOD activity in human semen and seminal plasma.

The aim of the present study was to measure zinc (Zn) and iron (Fe) concentration in human semen and superoxide dismutase (SOD) activity in seminal plasma and correlate the results with sperm quality. Semen samples were obtained from men (N = 168) undergoing routine infertility evaluation. The study design included two groups based on the ejaculate parameters. Group I (n = 39) consisted of males with normal ejaculate (normozoospermia), and group II (n = 129) consisted of males with pathological spermiogram. Seminal Zn and Fe were measured in 162 samples (group I, n = 38; group II, n = 124) and SOD activity in 149 samples (group I, n = 37; group II, n = 112). Correlations were found between SOD activity and Fe and Zn concentration, and between Fe and Zn concentration. SOD activity was negatively associated with volume of semen and positively associated with rapid progressive motility, nonprogressive motility, and concentration. Negative correlation was stated between Fe concentration and normal morphology. Mean SOD activity in seminal plasma of semen from men of group I was higher than in seminal plasma of semen from men of group II. Fe concentration was higher in teratozoospermic males than in males with normal morphology of spermatozoa in group II. Our results suggest that Fe may influence spermatozoa morphology.

Effect of second and third generation oral contraceptives on C-reactive protein, lipids and apolipoproteins in young, non-obese, non-smoking apparently healthy women.

OBJECTIVE: Third generation oral contraceptives (OC) may increase the risk of cardiovascular events in healthy young women. DESIGN AND METHODS: We assessed the effect of second and third generation OC on CRP, lipids and apolipoproteins in 128 women. RESULTS: CRP was significantly higher in third generation contraceptive users. The main determinant of CRP in OC users was triglycerides. CONCLUSIONS: Young women using oral contraceptives, especially third generation formulas, might not be free of cardiovascular risk having increased CRP concentration.