Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents.

Obesity is associated with chronic low-grade inflammation that eventually leads to metabolic complications. Extracellular DNA (ecDNA) is a damage-associated molecular pattern. Extracellular mitochondrial DNA can activate innate immunity. We hypothesized that ecDNA, especially of mitochondrial origin, could be associated with components of the metabolic syndrome in young healthy probands. In a cross-sectional study, healthy adolescents (n = 1,249) provided blood samples. Anthropometric data, blood pressure, and blood counts were assessed. In addition, biochemical analysis of sera or plasma was conducted, including the quantification of advanced oxidation protein products (AOPPs) as a marker of oxidative stress induced by neutrophil or monocyte activation. Plasma ecDNA was isolated and measured by fluorometry. Nuclear and mitochondrial DNA were quantified by real-time PCR. Males had higher total plasma ecDNA [15 (11-21) vs. 11 (8-17) ng/mL; median (interquartile range)], nuclear [1,760 (956-3,273) vs. 1,153 (600-2,292) genome equivalents (GE)/mL], and mitochondrial [37,181 (14,836-90,896) vs. 30,089 (12,587-72,286) GE/mL] DNA. ecDNA correlated positively with the continuous metabolic syndrome score (r = 0.158 for males and r = 0.134 for females). Stronger correlations were found between ecDNA of mitochondrial origin and AOPP (r = 0.202 and 0.186 for males and females, respectively). Multivariate regression analysis revealed associations of nuclear DNA with leukocyte and erythrocyte counts. The results of this study of healthy adolescents show that circulating ecDNA is associated with the risk of metabolic syndrome, not with obesity per se. The association between mitochondrial ecDNA and AOPP requires further attention as it supports a potential role of mitochondria-induced sterile inflammation in the pathogenesis of the metabolic syndrome.

Estimation of the proportion of metabolic syndrome-free subjects on high cardiometabolic risk using two continuous cardiometabolic risk scores: a cross-sectional study in 16- to 20-year-old individuals.

In contrast to the dichotomous classification of metabolic syndrome, continuous metabolic syndrome scores enable to assess cardiometabolic burden in metabolic syndrome-free individuals. Using receiver operating characteristics analysis, discrimination power of continuous metabolic syndrome score calculated from population-based Z-scores or individual measures corrected to the accepted international standards for presence/absence of metabolic syndrome was assessed. Calculated cutoff values were used to estimate the proportions of metabolic syndrome-free subjects presenting high cardiometabolic risk. Clinical data were collected from 2331 (52% females) 16- to 20-year-old subjects. Receiver operating characteristics analyses showed an acceptable performance of both scores to classify metabolic syndrome presence: area under the curve (97-98%), sensitivity (95-100%), and specificity (86-96%). Compared with the prevalence of metabolic syndrome, proportions of metabolic syndrome-free subjects on high cardiometabolic risk, e.g., presenting continuous scores ≥ cutoff points, were about 3-fold higher in males, and 4-fold higher in females. Both scores correlated significantly with markers of cardiometabolic risk.Conclusion: Continuous cardiometabolic syndrome scores are practical tools to evaluate cardiometabolic risk in subjects not presenting metabolic syndrome. Accuracy, simplicity, and ability to classify metabolic syndrome-free subjects on high cardiometabolic risk make continuous metabolic syndrome score derived from international standards convenient for use in research and clinical practice. What is Known: • Dichotomous classification of metabolic syndrome is simple but not suitable for assessment of cardiometabolic burden in metabolic syndrome-free subjects. This prompted implementation of continuous scores, which are generally sample-specific. Score based on internationally accepted standards allows for comparison between populations and studies. • The performance of different continuous metabolic syndrome scores to assess the prevalence of metabolic syndrome-free subjects presenting high cardiometabolic burden has not been compared yet. What is New: • We compared the discrimination power of sample-specific Z-score-derived continuous metabolic syndrome score and that calculated based on internationally accepted standards for presence or absence of metabolic syndrome in young subjects. • The prevalence of metabolic syndrome-free subjects presenting high cardiometabolic risk was estimated using the cutoff points of continuous metabolic syndrome scores derived from the analyses of receiver operating characteristic curves.

Gender-associated differences in the prevalence of central obesity using waist circumference and waist-to-height ratio, and that of general obesity, in Slovak adults.

OBJECTIVES: Central obesity represents an increased risk to develop cardiovascular diseases. Guidelines of international societies suggest estimating central obesity by measuring waist circumference (WC). Robust statistical data in literature provide evidence on the superiority of waist-to-height ratio (WHtR) over WC and body mass index (BMI) for detecting cardiometabolic risk in both genders. Based on measurements of weight, height and waist circumference we compared the prevalence of central obesity using both the above mentioned criteria in the apparently healthy Slovak adults, and compared the prevalence of central obesity to that of general obesity (BMI). METHODS: Data collected from 5,184 individuals (45% males) aged ≥18 years in four cross-sectional studies carried out between the years 2009-2012 were subjected to secondary analysis. RESULTS: Waist circumference underestimated central obesity in males and overestimated in females: 37.3% of males and 41.8% of females presented central obesity according to WC, 54.2% males and 34.9% females according to WHtR. 17.3% of males centrally obese according to WC present WHtR < 0.5; while 7.8% of females centrally obese according to their WHtR do not display increased WC. The frequency of central obesity increased with age. According to BMI, the prevalence of overweight was 39% in males and 22% in females; that of obesity was 17% and 15%, respectively. CONCLUSION: The prevalence of central obesity estimated using WC vs. WHtR differs significantly in Slovak adults. WHtR is considered superior for detection of the risk of future development of cardiovascular afflictions. Thus, further studies addressing the gender-associated discordance of central obesity measures are required to determine whether our results are consistent across geographical regions and ethnic groups.

Association between metabolically healthy central obesity in women and levels of soluble receptor for advanced glycation end products, soluble vascular adhesion protein-1, and the activity of semicarbazide-sensitive amine oxidase.

AIM: To determine the levels of circulating soluble receptor for advanced glycation end products (sRAGE), as a biomarker of risk of metabolic syndrome and cardiovascular disease development in centrally obese (CO) women considered metabolically healthy (COH) in comparison with those metabolically unhealthy (COU). METHODS: 47 lean healthy, 17 COH (presenting waist-to-height ratio ≥0.5 but not elevated blood pressure, atherogenic lipid profile, and insulin resistance), and 50 COU (CO presenting ≥2 risk factors) women aged 40-45 years were included. Anthropometric characteristics, blood chemistry and hematology data, adipokines, markers of inflammation, sRAGE, soluble vascular adhesion protein-1 (sVAP-1), and the activity of semicarbazide sensitive amine oxidase (SSAO) were determined. RESULTS: Central obesity associated with low sRAGE levels (lean healthy: 1503±633 pg/mL; COH: 1103±339 pg/mL, P<0.05; COU: 1106±367 ng/mL, P<0.0.1), hyperleptinemia, and elevated markers of inflammation irrespective of the presence or absence of cardiometabolic risk factors. COU women presented high adiponectin levels. SVAP-1 concentrations and the activity of SSAO were similar in all 3 groups. CONCLUSION: COH women present abnormalities in non-standard markers of cardiometabolic risk (sRAGE, leptin, high sensitive C-reactive protein), supporting the view that there is no healthy pattern of obesity. The clinical impact of our findings for future prognosis of metabolically healthy obese subjects remains to be elucidated in longitudinal studies.

Correlation among soluble receptors for advanced glycation end-products, soluble vascular adhesion protein-1/semicarbazide-sensitive amine oxidase (sVAP-1) and cardiometabolic risk markers in apparently healthy adolescents: a cross-sectional study.

In non-diabetics, low levels of soluble receptor for advanced glycations end products (sRAGE) associate with an increased risk of development of diabetes, cardiovascular afflictions, or death. The majority of studies in non-diabetics report an inverse relationship between measures of obesity, cardiometabolic risk factors and sRAGE and/or endogenous secretory RAGE (esRAGE) levels. To elucidate whether this inconsistency is related to the metabolically healthy obese phenotype, or a different impact of the risk factors in presence and absence of obesity, we analyzed data from 2206 apparently healthy adolescents (51 % girls) aged 15-to-19 years. The association of sRAGE levels with soluble vascular adhesion protein-1/semicarbazide sensitive amine oxidase (sVAP-1/SSAO) was also investigated. Centrally obese, including metabolically healthy, adolescents present significantly lower sRAGE and esRAGE, but not sVAP-1, levels in comparison with their lean counterparts. An increasing number of cardiometabolic risk factors did not associate with significant changes in sRAGE, esRAGE or sVAP-1 levels either in lean or in obese subjects. In multivariate analyses, WHtR, hsCRP, markers of glucose homeostasis, renal function, adiponectin, and sVAP-1 associated significantly with sRAGE and esRAGE. SVAP-1 correlated significantly with glycemia, adiponectin, hsCRP, and sRAGE. Thus, in adolescents, a decline in sRAGE and esRAGE precedes the development of metabolic syndrome. When combined, standard and non-standard cardiometabolic risk factors explain only minor proportion in a variability of sRAGE and esRAGE (8 %-11 %); or sVAP-1 (12 %-20 %). Elucidation of pathogenetic mechanisms underlying early decline in sRAGE and esRAGE levels in obese adolescents and their clinical impact with regard to future cardiometabolic health requires further studies.

Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats.

AIM: To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. METHODS: At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. RESULTS: MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. CONCLUSION: Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life.

[Association between asymptomatic hyperuricaemia and metabolic syndrome in the adolescents]. / Asymptomatická hyperurikémia a metabolický syndróm u mladistvých.

In humans, uric acid represents a biologically active end-product of purine nucleotides. Several studies in children and adolescents documented an association between hyperuricaemia and the components metabolic syndrome. High intake of fructose-sweetened beverages might increase uricaemia, since fructose is the only saccharide which metabolism results in the formation of uric acid. Current knowledge does not allow distinguishing whether hyperuricaemia is causally related to the components of metabolic syndrome, or rather represents a marker of an enhanced risk, and poor outcome. No guidelines exist whether or not to treat asymptomatic hyperuricaemia in the adolescents. Randomized controlled prospective clinical studies are needed to elucidate whether uric acid-lowering management would beneficially affect the prevalence of metabolic syndrome, and the incidence of cardiovascular disease.

Association of Leukocyte, Erythrocyte, and Platelet Counts with Metabolic Syndrome and Its Components in Young Individuals without Overt Signs of Inflammation: A Cross-Sectional Study.

The presence of metabolic syndrome (MetS) increases the risk of developing type 2 diabetes, cardiovascular diseases, and mortality. MetS is associated with increased leukocyte or erythrocyte counts. In 16- to 20-year-old males (n = 1188) and females (n = 1231) without signs of overt inflammation, we studied whether the presence of MetS and its components results in elevated blood cell counts. The leukocyte, erythrocyte, and thrombocyte counts significantly but weakly correlated with the continuous MetS score, MetS components, uric acid, and C-reactive protein levels both in males (r = -0.09 to 0.2; p < 0.01) and females (r = -0.08 to 0.2; p < 0.05). Subjects with MetS had higher leukocyte (males: 6.2 ± 1.3 vs. 6.9 ± 1.2 × 109/L; females 6.6 ± 1.5 vs. 7.5 ± 1.6 × 109/L; p < 0.001), erythrocyte (males: 5.1 ± 0.3 vs. 5.3 ± 0.3 × 1012/L; females: 4.5 ± 0.3 vs. 4.8 ± 0.3 × 1012/L; p < 0.001), and platelet counts (males: 245 ± 48 vs. 261 ± 47 × 109/L; females: 274 ± 56 vs. 288 ± 74 × 109/L; p < 0.05) than those without MetS. With the exception of platelet counts in females, the blood counts increased with the number of manifested MetS components. Phenotypes with the highest average leukocyte, erythrocyte, or platelet counts differed between sexes, and their prevalence was low (males: 0.3% to 3.9%; females: 1.2% to 2.7%). Whether functional changes in blood elements accompany MetS and whether the increase in blood counts within the reference ranges represents a risk for future manifestation of cardiometabolic diseases remain unanswered.

Association of Atherogenic Index of Plasma with Cardiometabolic Risk Factors and Markers in Lean 14-to-20-Year-Old Individuals: A Cross-Sectional Study.

Cardiometabolic risk factors at a young age pose a significant risk for developing atherosclerotic cardiovascular disease in adulthood. Atherogenic dyslipidemia is highly associated with obesity and metabolic syndrome already in young age. It remains unclear whether cardiometabolic risk factors associate with the atherogenic index of plasma (AIP = log (TAG/HDL-C) in lean subjects with low atherogenic risk. As both the AIP and markers of cardiometabolic risk are continuous variables, we expected their association to be linear before the manifestation of obesity and atherogenic dyslipidemia. We analyzed the prevalence of increased atherogenic risk (AIP ≥ 0.11) in 2012 lean 14-to-20-year-old subjects (55% females) and the trends of cardiometabolic risk factors across the quartiles (Q) of AIP in a subgroup of 1947 (56% females) subjects with low atherogenic risk (AIP < 0.11). The prevalence of AIP ≥ 0.11 reached 3.6% in females and 8.5% in males. HDL-C, non-HDL-C, triglycerides, and the continuous metabolic syndrome score showed a stepwise worsening across the AIP quartiles in both sexes. Measures of obesity and insulin resistance were worse in Q4 vs. Q1 groups, and leukocyte counts were higher in Q4 and Q3 vs. Q1. Females in Q4 presented with a higher C-reactive protein and lower adiponectin, estradiol, and testosterone levels. The multivariate regression model selected non-HDL-C, QUICKI, and erythrocyte counts as significant predictors of AIP in males; and non-HDL-C and C-reactive protein in females. A question arises whether the lean individuals on the upper edge of low atherogenic risk are prone to earlier manifestation of metabolic syndrome and shift to the higher AIP risk group.

Severe gestational diabetes mellitus in lean dams is associated with low IL-1α levels and affects the growth of the juvenile mouse offspring.

We investigated how maternal gestational diabetes (GDM) impacts the metabolic status of offspring. GDM was induced in CD1 mice consuming a fast-food diet (FFD) by repeated low-dose streptozotocin injections before mating. Offspring of normoglycemic standard chow or the FFD consuming dams served as controls. In 4-week-old offspring weaned to standard chow, plasma concentrations of extracellular DNA, inflammatory markers, and parameters of the cardiometabolic status (glycemia, liver lipid content; body, organ, and fat weight) were determined. Two-factor analysis of variance indicated that the male offspring of GDM dams manifest postnatal growth retardation and lower relative kidney weight. Regardless of sex, GDM offspring manifest the lowest IL-1α levels, and other inflammatory markers showed mild and inconsistent alterations. Offspring of dams consuming the FFD displayed higher liver triacylglycerols content. The three groups of offspring showed no significant differences in glycemia and extracellular DNA. Partial least squares-discriminant analysis indicated that male GDM offspring present lower kidney, body, and brown adipose tissue weights; lower IL-1α levels, and higher concentrations of GM-CSF and IL-10 compared with their FFD counterparts. The model failed to select discriminative variables in females. In conclusion, in mice, maternal GDM in the absence of obesity adversely affects the early growth of juvenile male offspring.

Association of Inflammatory and Oxidative Status Markers with Metabolic Syndrome and Its Components in 40-to-45-Year-Old Females: A Cross-Sectional Study.

Oxidative stress and sterile inflammation play roles in the induction and maintenance of metabolic syndrome (MetS). This study cohort included 170 females aged 40 to 45 years who were categorized according to the presentation of MetS components (e.g., central obesity, insulin resistance, atherogenic dyslipidemia, and elevated systolic blood pressure) as controls not presenting a single component (n = 43), those with pre-MetS displaying one to two components (n = 70), and females manifesting MetS, e.g., ≥3 components (n = 53). We analyzed the trends of seventeen oxidative and nine inflammatory status markers across three clinical categories. A multivariate regression of selected oxidative status and inflammatory markers on the components of MetS was performed. Markers of oxidative damage (malondialdehyde and advanced-glycation-end-products-associated fluorescence of plasma) were similar across the groups. Healthy controls displayed lower uricemia and higher bilirubinemia than females with MetS; and lower leukocyte counts, concentrations of C-reactive protein, interleukine-6, and higher levels of carotenoids/lipids and soluble receptors for advanced glycation end-products than those with pre-MetS and MetS. In multivariate regression models, levels of C-reactive protein, uric acid, and interleukine-6 were consistently associated with MetS components, although the impacts of single markers differed. Our data suggest that a proinflammatory imbalance precedes the manifestation of MetS, while an imbalance of oxidative status accompanies overt MetS. Further studies are needed to elucidate whether determining markers beyond traditional ones could help improve the prognosis of subjects at an early stage of MetS.

The Presence of Hyperhomocysteinemia Does Not Aggravate the Cardiometabolic Risk Imposed by Hyperuricemia in Young Individuals: A Retrospective Analysis of a Cross-Sectional Study.

BACKGROUND: Little research has been conducted into the effects of the combined manifestation of hyperuricemia and hyperhomocysteinemia on cardiometabolic risk factors and markers in young subjects. METHODS: 1298 males and 1402 females, 14-to-20-year-olds, were classified into four groups: 1/normouricemic/normohomocysteinemic, 2/normouricemic/hyperhormohomocysteinemic, 3/hyperuricemic/normohomocysteinemic, and 4/hyperuricemic/hyperhomocysteinemic. Anthropometric measures, blood pressure, plasma glucose, insulin, lipids, markers of renal function, C-reactive protein, asymmetric dimethylarginine, and blood counts were determined. RESULTS: Hyperuricemic males (but not females) had higher odds for hyperhomocysteinemia than normouricemic ones (OR: 1.8; 95% CI: 1.4-2.3; p < 0.001). Homocysteine and uric acid levels correlated directly (males: r = 0.076, females: r = 0.120; p < 0.01, both). Two-factor analysis of variance did not reveal a significant impact of hyperhomocysteinemia on any of the investigated cardiometabolic variables in females; in males, hyperuricemia and hyperhomocysteinemia showed a synergic effect on asymmetric dimethylarginine levels. Among four groups, subjects concurrently manifesting hyperuricemia and hyperhomocysteinemia did not presented the highest continuous metabolic syndrome score-a proxy measure of cardiometabolic risk; neither the multivariate regression model indicated a concurrent significant effect of uric acid and homocysteine on continuous metabolic syndrome score in either sex. CONCLUSION: In young healthy subjects, hyperhomocysteinemia does not aggravate the negative health effects imposed by hyperuricemia.

Lean insulin-resistant young adults display increased cardiometabolic risk: A retrospective cross-sectional study.

AIM: We investigated whether lean insulin-resistant individuals manifest increased cardiometabolic risk. METHODS: 2,341 (51.8% females) healthy 16-23-year-old subjects were categorized as lean or overweight/obese; and insulin-sensitive or insulin-resistant, and compared. RESULTS: In both sexes, lean insulin-sensitive and insulin-resistant subjects displayed similar measures of obesity (e.g., males, waist-to-height ratio: lean insulin-sensitive: 0.42 ± 0.03, lean insulin-resistant: 0.43 ± 0.03, overweight/obese insulin-sensitive: 0.49 ± 0.05, overweight/obese insulin-resistant: 0.53 ± 0.06). Lean insulin-sensitive individuals were more insulin-sensitive compared with their overweight/obese peers; insulin-resistant groups presented similar insulin-sensitivity (males, the Quantitative insulin-sensitivity check index (QUICKI): lean insulin-sensitive: 0.354 ± 0.022, lean insulin-resistant: 0.304 ± 0.013, overweight/obese insulin-sensitive: 0.343 ± 0.019, overweight/obese insulin-resistant: 0.299 ± 0.015). The two-factor analysis of variance indicated an independent effect of insulin sensitivity, overweight/obesity, and their interaction on the continuous metabolic syndrome score (p < 0.001, all; males, lean insulin-sensitive: 1.87 ± 0.35, lean insulin-resistant: 2.14 ± 0.42, overweight/obese insulin-sensitive: 2.15 ± 0.40, overweight/obese insulin-resistant: 2.75 ± 0.69). C-reactive protein, leukocyte count, and glomerular filtration rate in both sexes; uric acid, asymmetric dimethyl-arginine, and soluble vascular adhesion protein-1 in males; and soluble receptor for advanced glycation end-products in females were independently associated with insulin resistance. Among phenotypes associated with low QUICKI, the distribution of insulin-resistant individuals was random. CONCLUSION: Later clinical consequences of insulin resistance in lean subjects remain to be elucidated in longitudinal studies.

Association of α-Dicarbonyls and Advanced Glycation End Products with Insulin Resistance in Non-Diabetic Young Subjects: A Case-Control Study.

α-Dicarbonyls and advanced glycation end products (AGEs) may contribute to the pathogenesis of insulin resistance by a variety of mechanisms. To investigate whether young insulin-resistant subjects present markers of increased dicarbonyl stress, we determined serum α-dicarbonyls-methylglyoxal, glyoxal, 3-deoxyglucosone; their derived free- and protein-bound, and urinary AGEs using the UPLC/MS-MS method; soluble receptors for AGEs (sRAGE), and cardiometabolic risk markers in 142 (49% females) insulin resistant (Quantitative Insulin Sensitivity Check Index (QUICKI) ≤ 0.319) and 167 (47% females) age-, and waist-to-height ratio-matched insulin-sensitive controls aged 16-to-22 years. The between-group comparison was performed using the two-factor (sex, presence/absence of insulin resistance) analysis of variance; multiple regression via the orthogonal projection to latent structures model. In comparison with their insulin-sensitive peers, young healthy insulin-resistant individuals without diabetes manifest alterations throughout the α-dicarbonyls-AGEs-sRAGE axis, dominated by higher 3-deoxyglucosone levels. Variables of α-dicarbonyls-AGEs-sRAGE axis were associated with insulin sensitivity independently from cardiometabolic risk markers, and sex-specifically. Cleaved RAGE associates with QUICKI only in males; while multiple α-dicarbonyls and AGEs independently associate with QUICKI particularly in females, who displayed a more advantageous cardiometabolic profile compared with males. Further studies are needed to elucidate whether interventions alleviating dicarbonyl stress ameliorate insulin resistance.

Creatinine-Based Formulae Poorly Match in the Classification of Hypofiltration or Hyperfiltration in a General Population of Adolescents: A Retrospective Analysis of a Cross-Sectional Study.

Pediatric formulae to estimate glomerular filtration rate (eGFR) give a broad range of values. Their consistency in assigning the subjects as hypofiltrating or hyperfiltrating is unknown. In 1993 apparently healthy adolescents (53.4% females) aged 14-17 years, we investigated the concordance of six creatinine-based formulae in the classification of the subjects into ≤ 5th or ≥95th percentile of eGFR, and the between-groups difference in the prevalence of cardiometabolic risk factors. Mean eGFR varied between 77 and 121 mL/min/1.73 m2. Arbitrary setting of hypofiltration or hyperfiltration to 5% returned 46 males and 53 females. At least one formula classified 89 males and 99 females as hypofiltrating and 105 males and 114 females as hyperfiltrating. All six formulae concordantly classified 15 males and 17 females as hypofiltrating and 9 and 14, respectively, as hyperfiltrating. Pairwise, formulae consistently classified hypofiltration in 42-87% of subjects with hyperfiltration in 28-94%. According to two out of the six formulae, hyperfiltration was associated with an increased prevalence of obesity and obesity-associated comorbidities. Hypofiltrating subjects did not manifest chronic kidney disease-associated comorbidities. Further studies in different populations of healthy adolescents are needed before it is possible to conclude which creatinine-based formula is appropriate for the classification of hypofiltration and hyperfiltration in nonclinical cohorts.

Neurodevelopmental testing of mice in the neonatal period does not affect their locomotor activity, depressive- and anxiety-like behaviour in adolescence.

Neonatal life is a sensitive period of brain plasticity. There are concerns that pre-weaning handling may therefore alter behavioural phenotype in adolescence or adulthood. Since neurodevelopment tests require daily manipulation with pups, later behavioural outcomes might be biased by repeated handling during suckling period. The aim of our study was to assess whether daily neurodevelopmental testing would cause alterations in behavioural phenotype. Sixty-four CD1 mice were randomized to tested and not tested group. In the tested group, maturation of physical features and neurodevelopment were monitored daily from postnatal day 1-21 between 9 and 11 AM. After weaning, battery of behavioural tests to monitor anxiety-like, depressive, or repetitive behaviour was performed in all mice. We revealed no significant between-group differences in performance of these tests. Our data did not confirm the assumption that early neurodevelopment testing during suckling period affects behavioural phenotype in adolescence.

Elevated blood pressure-associated cardiometabolic risk factors and biomarkers in 16-23 years old students with or without metabolic abnormalities.

In obesity, cardiometabolic risk markers show worsening trends with increasing blood pressure (BP). We assumed that risk markers show similar trends across BP categories (normotension, high normal BP, hypertension) in metabolic abnormalities-free subjects (without obesity, insulin resistance, atherogenic dyslipidemia, hyperuricemia, microinflammation) and those presenting them. Data from 2547 (48.1% males) subjects aged 16-23 years were analyzed. The prevalence of males increased across BP categories. Forty-seven percent of individuals with elevated BP were metabolic abnormalities-free. Among 1461 metabolic abnormalities-free subjects, 9% had high normal BP, and 4% hypertension; among 1086 individuals presenting metabolic abnormalities, the prevalence reached 13% and 6%, respectively, (p < 0.001). Both groups displayed similar BP values in corresponding BP categories and significant trends in markers of adiposity, insulin resistance, HDL-cholesterol, atherogenic index of plasma, uric acid, adiponectinemia, and antioxidant capacity of plasma across BP categories. In metabolic abnormalities-free individuals, also significant trends in soluble receptors for advanced glycation end products were revealed. Continuous metabolic syndrome score, a measure of cardiometabolic risk, increased across BP categories regardless of presence or absence of metabolic abnormalities. Multivariate regression models selected male gender, fat-free mass, and uric acid as significant independent predictors for determining BP. Our data emphasize that having a BP outside the normal range significantly worsens risk for cardiometabolic disease in young individuals even if the thresholds for any of the risk factors are not exceeded. Longitudinal studies are needed to assess whether in patients with elevated BP the prognosis of adverse outcomes differs between those presenting and not presenting metabolic abnormalities.

Asymptomatic Hyperuricemia Associates with Cardiometabolic Risk Indicators in Overweight/Obese but Not in Lean Adolescents.

PURPOSE: In overweight/obese adolescents, asymptomatic hyperuricemia is associated with increased prevalence of metabolic syndrome, its components, and a higher cardiometabolic risk. Whether similar associations exist in lean hyperuricemic adolescents is unknown. SUBJECTS AND METHODS: In 2424 adolescents (51.9% females) aged 16-19 years, anthropometric variables, blood pressure, uric acid, glucose, insulin, lipid profile, inflammatory markers, and renal function were determined. Continuous cardiometabolic score was calculated. Normouricemic vs hyperuricemic subjects were compared among lean and overweight/obese individuals of both sexes. RESULTS: Females (5.4%) and males (13.3%) presented with hyperuricemia; among them 63% of females and 53% of males were lean. In both sexes, hyperuricemic lean and hyperuricemic overweight/obese adolescents displayed similar uric acid concentrations (eg, males: 455±30 vs 461±32 µmol/L, respectively, p=0.933). Lean normouricemic adolescents manifested significantly lower uric acid levels than their overweight/obese peers (eg, males: 333±46 vs 357±41 µmol/L, respectively, p<0.001). Lean normouricemic and hyperuricemic subjects presented similar cardiometabolic score (eg, males: 2.60±0.67 vs 2.64±0.60, respectively, p=0.998); among overweight/obese adolescents those with hyperuricemia displayed higher scores compared with their normouricemic counterparts (eg, males: 3.36±1.04 vs 4.21±1.65, respectively, p<0.001). A decision-tree model revealed phenotypes associated with higher uricemia, however, distribution of individuals with hyperuricemia among phenotypes was random. CONCLUSION: In lean adolescents, hyperuricemia is not associated with cardiometabolic profile indicating an increased risk. Existence of this rather prevalent phenotype remains undetected unless lean and overweight/obese subjects are analyzed separately. Longitudinal studies are needed to elucidate the potential clinical consequences of asymptomatic hyperuricemia in lean subjects in later life.

Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers.

Kidney disease represents a serious global health problem. One of the main concerns is its late diagnosis, only feasible in a progressed disease state. The lack of a clinical manifestation in the early stages and the fact that the commonly measured parameters of renal function are markedly reduced only during advanced stages of the disease are the main cause. Changes at the molecular level of the kidney tissue occur even before nitrogenous substances, such as creatinine and urea, start to accumulate in the blood. Renal proximal tubules contain a large number of mitochondria and are critical for the energy-demanding process of reabsorption of water and solutes. Mitochondria are the largest producers of oxygen radicals, which, in turn, increase the susceptibility of kidneys to oxidative stress-induced damage. Free radicals and prooxidants produced during acute or chronic kidney injury may further aggravate the course of the disease and play a role in the pathogenesis of subsequent complications. Prevention might be the solution in CKD, but patients are often reluctant to undergo preventive examinations. Noninvasive markers and the possibility to obtain samples at home might help to increase compliance. This review will provide an overview of the possible uses of markers of oxidative status in noninvasive biofluids in patients with renal disease.

Sex Differences in Association of Elevated Blood Pressure with Variables Characterizing Cardiometabolic Risk in Young Subjects with or Without Metabolic Abnormalities.

Males present higher blood pressure (BP) values, higher prevalence of elevated BP, and a different prevalence of cardiometabolic risk factors when compared with females. We assumed that the trends of risk markers across BP categories (normotension, high normal BP, and hypertension) differ in young males and females, and between subjects without metabolic abnormalities (without obesity, insulin resistance, atherogenic dyslipidemia, hyperuricemia, or microinflammation) and those presenting them. Data from 2543 subjects (48% males) aged from 16 to 23 years were analyzed. The findings showed that 15% of males and 4% of females presented high normal BP while 9% and 1%, respectively, had hypertension. In males, variables characterizing obesity status, insulin sensitivity, atherogenic dyslipidemia, uric acid, adiponectin, a soluble receptor for advanced glycation end-products, and leukocyte counts showed worsening trends across BP categories. Females presented significant trends only for obesity measures, LDL-cholesterol, and non-HDL-cholesterol. Across BP categories, trends of variables characterizing cardiometabolic risk differed among abnormalities-free and presenting males. The multivariate model selected measures of central obesity, atherogenic dyslipidemia, insulin resistance, and uric acid as significant predictors of BP in both genders, and C-reactive protein in females. Sex differences in measures of cardiovascular health in juveniles may remain undiscovered unless two sexes are analyzed separately. These differences may have implications for sex-specific disease risk in adulthood.