Metabolic profiling of fatty liver in young and middle-aged adults : Cross-sectional and prospective analyses of the Young Finns Study

Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34-49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P <0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48-6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51-3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30-0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32-0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P <0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491-500).Peer reviewe

The type of the functional cardiovascular response to upright posture is associated with arterial stiffness: a cross-sectional study in 470 volunteers

In a cross-sectional study we examined whether the haemodynamic response to upright posture could be divided into different functional phenotypes, and whether the observed phenotypes were associated with known determinants of cardiovascular risk. METHODS: Volunteers (n = 470) without medication with cardiovascular effects were examined using radial pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis. Based on the passive head-up tilt induced changes in systemic vascular resistance and cardiac output, the principal determinants of blood pressure, a cluster analysis was performed. RESULTS: The haemodynamic response could be clustered into 3 categories: upright increase in vascular resistance and decrease in cardiac output were greatest in the first (+45 % and -27 %, respectively), smallest in the second (+2 % and -2 %, respectively), and intermediate (+22 % and -13 %, respectively) in the third group. These groups were named as 'constrictor' (n = 109), 'sustainer' (n = 222), and 'intermediate' (n = 139) phenotypes, respectively. The sustainers were characterized by male predominance, higher body mass index, blood pressure, and also by higher pulse wave velocity, an index of large arterial stiffness, than the other groups (p < 0.01 for all). Heart rate variability analysis showed higher supine and upright low frequency/high frequency (LF/HF) ratio in the sustainers than constrictors, indicating increased sympathovagal balance. Upright LF/HF ratio was also higher in the sustainer than intermediate group. In multivariate analysis, independent explanatory factors for higher pulse wave velocity were the sustainer (p < 0.022) and intermediate phenotypes (p < 0.046), age (p < 0.001), body mass index (p < 0.001), and hypertension (p < 0.001). CONCLUSIONS: The response to upright posture could be clustered to 3 functional phenotypes. The sustainer phenotype, with smallest upright decrease in cardiac output and highest sympathovagal balance, was independently associated with increased large arterial stiffness. These results indicate an association of the functional haemodynamic phenotype with an acknowledged marker of cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT01742702.BioMed Central open acces

Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects

ad-up tilt. Methods Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20–72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease. Correlations were calculated, and results analysed according to resting HR tertiles. Results Higher resting HR was associated with elevated systolic and diastolic BP, lower stroke volume but higher cardiac output and work, and lower systemic vascular resistance, both supine and upright (p < 0.05 for all). Subjects with higher HR also showed lower supine and upright aortic pulse pressure and augmentation index, and increased resting pulse wave velocity (p < 0.001). Upright stroke volume decreased less in subjects with highest resting HR (p < 0.05), and cardiac output decreased less in subjects with lowest resting HR (p < 0.009), but clear hemodynamic differences between the tertiles persisted both supine and upright. Conclusions Supine and upright hemodynamic profile associated with higher resting HR is characterized by higher cardiac output and lower systemic vascular resistance. Higher resting HR was associated with reduced central wave reflection, in spite of elevated BP and arterial stiffness. The increased cardiac workload, higher BP and arterial stiffness, may explain why higher HR is associated with less favourable prognosis in populations.BioMed Central open acces

Metabolic profiling of fatty liver in young and middle-aged adults:cross-sectional and prospective analyses of the young Finns study

Abstract Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34–49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P &lt; 0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] 5 4.86 per 1 standard deviation, 95% confidence interval 3.48–6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51–3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30–0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32–0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P &lt; 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults

Česká republika: Evropská integrace a rozvoj ve struktuře obchodu

Trade structure changes over time as a result of fundamental changes within the country or the world around it. This thesis will investigate the case of Czech Republic in the period from the transition period till today with the foundation in classical and neoclassical trade theory. The trade structure will be analyzed in regard to trade partners, commodity structure, relative comparative advantages and degree of intra-industry trade within an industry or sector. It will provide basis for assessing the effects of increased European integration which the Czech Republic increasingly engaged itself in with the accession to the EU in 2004

Daily Liquorice Consumption for Two Weeks Increases Augmentation Index and Central Systolic and Diastolic Blood Pressure

<div><p>Background</p><p>Liquorice ingestion often elevates blood pressure, but the detailed haemodynamic alterations are unknown. We studied haemodynamic changes induced by liquorice consumption in 20 subjects versus 30 controls with average blood pressures of 120/68 and 116/64 mmHg, respectively.</p><p>Methods</p><p>Haemodynamic variables were measured in supine position before and after two weeks of liquorice consumption (daily glycyrrhizin dose 290–370 mg) with tonometric recording of radial blood pressure, pulse wave analysis, and whole-body impedance cardiography. Thirty age-matched healthy subjects maintaining their normal diet were studied as controls.</p><p>Results</p><p>Two weeks of liquorice ingestion elevated peripheral and central systolic and diastolic blood pressure (by 7/4 and 8/4 mmHg, 95% confidence intervals [CI] 2-11/1-8 and 3-13/1-8, respectively, <i>P</i><0.05), and increased extracellular volume by 0.5 litres (<i>P</i><0.05 versus controls). Also augmentation index adjusted to heart rate 75/min (from 7% to 11%, 95% CI for change 0.3-7.5, <i>P</i><0.05) and aortic pulse pressure (by 4 mmHg, 95% CI 1-7, <i>P</i><0.05) were elevated indicating increased wave reflection from the periphery. In contrast, peripheral (−3/−0.3 mmHg) and central blood pressure (−2/−0.5 mmHg), aortic pulse pressure (−1 mmHg), and augmentation index adjusted to heart rate 75/min (from 9% to 7%) decreased numerically but not statistically significantly without changes in extracellular volume in the control group. Heart rate, systemic vascular resistance, cardiac output, and pulse wave velocity did not differ between the groups.</p><p>Conclusions</p><p>Two weeks of daily liquorice consumption increased extracellular volume, amplified pressure wave reflection from the periphery, and elevated central systolic and diastolic blood pressure.</p><p>Trial Registration</p><p>EU Clinical Trials Register EudraCT 2006-002065-39</p><p>ClinicalTrials.gov <a href="http://clinicaltrials.gov/ct2/show/NCT01742702" target="_blank">NCT01742702</a></p></div

Additional file 6: of The type of the functional cardiovascular response to upright posture is associated with arterial stiffness: a cross-sectional study in 470 volunteers

Table in pdf-format showing outcome of adjusted analyses of heart rate variability parameters in supine and upright positions using model 1 presented in Table 2. (PDF 13 kb

Flow diagram of the study.

<p>Flow diagram of the study.</p

Radial and aortic blood pressure, liquorice diet versus normal diet.

<p>Grey lines represent each individual, thick black line represents mean values of each variable. SBP, systolic blood pressure; DBP, diastolic blood pressure; <i>P</i> values between graphs are for the difference in the change of each variable between liquorice diet versus normal diet, <i>P</i> values in brackets are for the change within each group, n = 20 and 30 in the liquorice and normal diet groups, respectively.</p