Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein (CRP) served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple mediation analysis revealed that all three potential mediators played a role in mediating the association. However, in parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43-0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, -0.13; 95% CI, -0.31-0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, -0.003-0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

• Klíčová slova
• diabetes, insulin resistance, lipoprotein, mediation analysis,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: This survey aims to assess the implementation of recommendations from the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) by clinical biochemistry laboratories in Czechia and Slovakia in their policies for reporting low-density lipoprotein cholesterol (LDL-C) concentrations. MATERIALS AND METHODS: The web-based survey was distributed to all 383 Czech and Slovak clinical biochemistry laboratories that measure lipids by external quality assessment provider SEKK. A total of 17 single-answer questions were included. The questionnaire was focused on the detection and decision points in familial hypercholesterolemia (FH). All survey answers were taken into account. The laboratories followed the EFLM and EAS guidelines when they reported an interpretative comment considering FH diagnosis in adults. RESULTS: A total of 203 (53%) laboratories answered. Only 5% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 5.0 mmol/L in adults, and 3% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 4.0 mmol/L in children. Only 7% of laboratories reported goals for all cardiovascular risk categories (low, moderate, high, very high). Non-HDL cholesterol concentrations were calculated by 74% of responders. A significant number (51%) of participants did not measure apolipoprotein B, and 59% of laboratories did not measure lipoprotein(a). CONCLUSIONS: Only a small portion of laboratories from Czechia and Slovakia reported high LDL-C results with interpretative comments considering FH diagnosis in adults, the laboratories did not follow the guidelines.

• Klíčová slova
• HDL cholesterol, LDL cholesterol, apolipoprotein B, familial hypercholesterolemia, lipoprotein(a), technical report,
• MeSH
• ateroskleróza * MeSH
• cholesterol MeSH
• dítě MeSH
• dospělí MeSH
• hyperlipoproteinemie typ II * diagnóza   MeSH
• laboratoře MeSH
• LDL-cholesterol MeSH
• lidé MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Slovenská republika MeSH
• Názvy látek
• cholesterol MeSH
• LDL-cholesterol MeSH

Background: Severe hypercholesterolemia is associated with an increase in the risk of developing atherosclerotic cardiovascular disease. The aim of this analysis was to assess longitudinal trends in severe dyslipidemia (defined as total cholesterol > 8 mmol/L or LDL-cholesterol > 5 mmol/L) in a representative population sample of the Czech Republic and to analyze the longitudinal trends in the basic characteristics of individuals with severe dyslipidemia. Methods: Seven independent cross-sectional surveys were organized in the Czech Republic to screen for major cardiovascular risk factors (from 1985 to 2015-2018). A total of 20,443 randomly selected individuals aged 25-64 years were examined. Results: The overall prevalence of severe dyslipidemia was 6.6%, with a significant downward trend from the fifth survey onwards (2000/2001). Over the study period of 30+ years, the individuals with severe dyslipidemia became older, increased in BMI, and did not change their smoking habits. Total cholesterol and non-HDL-cholesterol decreased significantly in both sexes throughout the duration of the study. Conclusions: Despite a significant improvement in lipids in the Czech Republic from 1985, substantially contributing to the decline in cardiovascular mortality, the number of individuals with severe dyslipidemia remained high, and in most cases, they were newly detected during our screening examinations and were thus untreated.

• Klíčová slova
• HDL cholesterol, LDL cholesterol, cross-sectional survey, familial hypercholesterolemia, population random sample, prevalence of severe dyslipidemia, total cholesterol,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Despite better accessibility of the effective lipid-lowering therapies, only about 20% of patients at very high cardiovascular risk achieve the low-density lipoprotein cholesterol (LDL-C) goals. There is a large disparity between European countries with worse results observed for the Central and Eastern Europe (CEE) patients. One of the main reasons for this ineffectiveness is therapeutic inertia related to the limited access to appropriate therapy and suitable dosage intensity. Thus, we aimed to compare the differences in physicians' therapeutic decisions on alirocumab dose selection, and factors affecting these in CEE countries vs. other countries included in the ODYSSEY APPRISE study. METHODS: ODYSSEY APPRISE was a prospective, single-arm, phase 3b open-label (≥12 weeks to ≤30 months) study with alirocumab. Patients received 75 or 150 mg of alirocumab every 2 weeks, with dose adjustment during the study based on physician's judgment. The CEE group in the study included Czechia, Greece, Hungary, Poland, Romania, Slovakia, and Slovenia, which we compared with the other nine European countries (Austria, Belgium, Denmark, Finland, France, Germany, Italy, Spain, and Switzerland) plus Canada. RESULTS: A total of 921 patients on alirocumab were involved [modified intention-to-treat (mITT) analysis], including 114 (12.4%) subjects from CEE countries. Therapy in CEE vs. other countries was numerically more frequently started with lower alirocumab dose (75 mg) at the first visit (74.6 vs. 68%, p = 0.16). Since week 36, the higher dose was predominantly used in CEE patients (150 mg dose in 51.6% patients), which was maintained by the end of the study. Altogether, alirocumab dose was significantly more often increased by CEE physicians (54.1 vs. 39.9%, p = 0.013). Therefore, more patients achieved LDL-C goal at the end of the study (<55 mg/dl/1.4 mmol/L and 50% reduction of LDL-C: 32.5% vs. 28.8%). The only factor significantly influencing the decision on dose of alirocumab was LDL-C level for both countries' groups (CEE: 199.2 vs. 175.3 mg/dl; p = 0.019; other: 205.9 vs. 171.6 mg/dl; p < 0.001, for 150 and 75 mg of alirocumab, respectively) which was also confirmed in multivariable analysis (OR = 1.10; 95% CI: 1.07-1.13). CONCLUSIONS: Despite larger unmet needs and regional disparities in LDL-C targets achievement in CEE countries, more physicians in this region tend to use the higher dose of alirocumab, they are more prone to increase the dose, which is associated with a higher proportion of patients reaching LDL-C goals. The only factor that significantly influences decision whether to increase or decrease the dose of alirocumab is LDL-C level.

• Klíčová slova
• LDL-C, PCKS9 inhibition, alirocumab, therapy goals, therapy intensity,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Dysfunctional adipose tissue (AT) is known to contribute to the pathophysiology of metabolic disease, including type 2 diabetes mellitus (T2DM). This dysfunction may occur, in part, as a consequence of gut-derived endotoxaemia inducing changes in adipocyte mitochondrial function and reducing the proportion of BRITE (brown-in-white) adipocytes. Therefore, the present study investigated whether endotoxin (lipopolysaccharide; LPS) directly contributes to impaired human adipocyte mitochondrial function and browning in human adipocytes, and the relevant impact of obesity status pre and post bariatric surgery. METHODS: Human differentiated abdominal subcutaneous (AbdSc) adipocytes from participants with obesity and normal-weight participants were treated with endotoxin to assess in vitro changes in mitochondrial function and BRITE phenotype. Ex vivo human AbdSc AT from different groups of participants (normal-weight, obesity, pre- and 6 months post-bariatric surgery) were assessed for similar analyses including circulating endotoxin levels. RESULTS: Ex vivo AT analysis (lean & obese, weight loss post-bariatric surgery) identified that systemic endotoxin negatively correlated with BAT gene expression (p < 0.05). In vitro endotoxin treatment of AbdSc adipocytes (lean & obese) reduced mitochondrial dynamics (74.6% reduction; p < 0.0001), biogenesis (81.2% reduction; p < 0.0001) and the BRITE phenotype (93.8% reduction; p < 0.0001). Lean AbdSc adipocytes were more responsive to adrenergic signalling than obese AbdSc adipocytes; although endotoxin mitigated this response (92.6% reduction; p < 0.0001). CONCLUSIONS: Taken together, these data suggest that systemic gut-derived endotoxaemia contributes to both individual adipocyte dysfunction and reduced browning capacity of the adipocyte cell population, exacerbating metabolic consequences. As bariatric surgery reduces endotoxin levels and is associated with improving adipocyte functionality, this may provide further evidence regarding the metabolic benefits of such surgical interventions.

• Klíčová slova
• Adipocyte browning, Bariatric surgery, Endotoxin, Human adipocytes, Lipopolysaccharide, Mitochondria, Obesity,
• MeSH
• diabetes mellitus 2. typu * MeSH
• endotoxemie * metabolismus   MeSH
• endotoxiny metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy MeSH
• obezita metabolismus   MeSH
• tukové buňky metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• endotoxiny MeSH
• lipopolysacharidy MeSH

OBJECTIVES: This study evaluates the effect of a 3-month calorie restriction (CR) without snacking on the anthropometric parameters, Homeostatic Model Assesment of Insulin Resistance (HOMA-IR), and lipid profiles of female office workers with overweight or obesity, whose physical activity was limited during the COVID-19 pandemic lockdown. MATERIAL AND METHODS: Forty-eight women aged 20-38 years (28.9±5.24) with low physical activity levels were divided into a non-snacking (NS) group (N = 21) and a snacking (S) group (N = 27) prior to the dietary intervention. Their daily energy intake during the intervention was lowered by 30% compared with the baseline level, and the proportion of polyunsaturated fatty acids and fiber in their diet was increased (to >30 g/day). The proportion of saturated fatty acids and simple carbohydrates was also reduced. The study participants were assessed at the baseline and post-intervention for anthropometric variables (body weight, body fat percentage BMI, waist circumference, hip circumference, waist-to-hip ratio) and the concentrations of insulin, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Moreover, the values for HOMA-IR, the atherogenic index of plasma (AIP), and the ratios of TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C were calculated. RESULTS: All anthropometric parameter values obtained post-intervention were lower than the baseline in both groups. The serum insulin concentration and HOMA-IR decreased respectively by an average of 6% and 25% in the NS group and 37% and 45% in the S group. The lipid profiles of all participants improved significantly, with the LDL-C concentration showing a more promising trend in the S group (decrease by 27%) than in the NS group (17%). CONCLUSIONS: The study showed that CR improved the anthropometric parameters, HOMA-IR index, and lipid profiles of all participants. Int J Occup Med Environ Health. 2022;35(6):693-706.

• Klíčová slova
• coronavirus pandemic, insulin resistance, lipid profile, low physical activity level, reduction diet, snacking,
• MeSH
• COVID-19 * MeSH
• HDL-cholesterol MeSH
• index tělesné hmotnosti MeSH
• inzulin MeSH
• inzulinová rezistence * MeSH
• kalorická restrikce MeSH
• kontrola infekčních nemocí MeSH
• LDL-cholesterol MeSH
• lidé MeSH
• nadváha MeSH
• obezita MeSH
• pandemie MeSH
• triglyceridy MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• HDL-cholesterol MeSH
• inzulin MeSH
• LDL-cholesterol MeSH
• triglyceridy MeSH

Non-alcoholic fatty liver disease (NAFLD) is linked to type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. The Rho/ROCK pathway had been involved in the pathophysiology of diabetic complications. This study was designed to assess the possible protective impacts of the Rho/Rho-associated coiled-coil containing protein kinase (Rho/ROCK) inhibitor fasudil against NAFLD in T2DM rats trying to elucidate the underlying mechanisms. Animals were assigned into control rats, non-treated diabetic rats with NAFLD, and diabetic rats with NAFLD that received fasudil treatment (10 mg/kg per day) for 6 weeks. The anthropometric measures and biochemical analyses were performed to assess metabolic and liver function changes. The inflammatory and oxidative stress markers and the histopathology of rat liver tissues were also investigated. Groups with T2DM showed increased body weight, serum glucose, and insulin resistance. They exhibited disturbed lipid profile, enhancement of inflammatory cytokines, and deterioration of liver function. Fasudil administration reduced body weight, insulin resistance, and raised liver enzymes. It improved the disturbed lipid profile and attenuated liver inflammation. Moreover, it slowed down the progression of high fat diet (HFD)-induced liver injury and reduced the caspase-3 expression. The present study demonstrated beneficial amelioration effect of fasudil on NAFLD in T2DM. The mechanisms underlying these impacts are improving dyslipidemia, attenuating oxidative stress, downregulated inflammation, improving mitochondrial architecture, and inhibiting apoptosis.

• MeSH
• diabetes mellitus 2. typu * komplikace   farmakoterapie   MeSH
• dieta s vysokým obsahem tuků škodlivé účinky   MeSH
• experimentální diabetes mellitus * komplikace   farmakoterapie   metabolismus   MeSH
• inzulinová rezistence * MeSH
• játra metabolismus   MeSH
• kinázy asociované s rho metabolismus   MeSH
• krysa rodu Rattus MeSH
• lipidy MeSH
• nealkoholová steatóza jater * farmakoterapie   patologie   MeSH
• tělesná hmotnost MeSH
• zánět metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fasudil MeSH Prohlížeč
• kinázy asociované s rho MeSH
• lipidy MeSH

To investigate the influence of beer consumption on levels of homocysteine (HCY), vitamin B6, B12, folic acid (FA), dimethylglycine (DMG), betaine (BET) and other selected markers. One hundred and sixteen male volunteers were enrolled in the study. A one-month period of alcohol abstinence was followed by a one month when participants drank 830 mL of alcoholic beer every day. After that phase, one month of alcohol abstinence followed. At the beginning and after every phase blood samples were taken and analysed. Ninety-three participants completed the study. After the phase of alcohol consumption, uric acid (UA) (p<0.0001), antioxidative capacity (AOC) (p=0.02), superoxide dismutase (SOD) (0.025), glutathione reductase (GRH) (0.0001), total cholesterol (p<0.0001), HDL-cholesterol (p<0.0001), Apolipoprotein-AI (ApoAI) (p<0.0001), LDL-cholesterol (p<0.039) and Apolipoprotein B (ApoB) (p<0.009) increased, while vitamin B12 (p=0.0001) and fibrinogen (p<0.0001) decreased. Other tested parameters (DMG, BET, vitamin B6 and FA) did not show any significant changes. UA changes and changes in AOC were statistically significantly correlated (r=0.52, p<0.0001). HCY, DMG and BET levels did not show any statistically significant changes after beer consumption, whereas some markers of redox metabolism increased (UA, AOC, SOD and GRH). A statistically significant correlation denotes the dependence of UA and AOC changes in connection with beer consumption.

• MeSH
• antioxidancia MeSH
• apolipoproteiny MeSH
• betain MeSH
• homocystein MeSH
• kyselina listová MeSH
• kyselina močová MeSH
• LDL-cholesterol MeSH
• lidé MeSH
• metylace MeSH
• oxidace-redukce MeSH
• pivo * MeSH
• superoxiddismutasa MeSH
• vitamin B6 * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antioxidancia MeSH
• apolipoproteiny MeSH
• betain MeSH
• homocystein MeSH
• kyselina listová MeSH
• kyselina močová MeSH
• LDL-cholesterol MeSH
• superoxiddismutasa MeSH
• vitamin B6 * MeSH

BACKGROUND: Obesity and hypertension represent serious health issues affecting the pediatric population with increasing prevalence. Hypovitaminosis D has been suggested to be associated with arterial hypertension. Serotonin by modulating nitric oxide synthase affect blood pressure regulation. The biological mechanism by which vitamin D specifically regulates serotonin synthesis was recently described. The aim of this paper is to determine the associations between vitamin D, serotonin, and blood pressure in obese children. METHODS: One hundred and seventy-one children were enrolled in the prospective cross-sectional study. Two groups of children divided according to body mass index status to obese (BMI ≥95th percentile; n = 120) and non-obese (n = 51) were set. All children underwent office and ambulatory blood pressure monitoring and biochemical analysis of vitamin D and serotonin. Data on fasting glucose, insulin, HOMA, uric acid, and complete lipid profile were obtained in obese children. RESULTS: Hypertension was found only in the group of obese children. Compared to the control group, obese children had lower vitamin D and serotonin, especially in winter. The vitamin D seasonality and BMI-SDS were shown as the most significant predictors of systolic blood pressure changes, while diastolic blood pressure was predicted mostly by insulin and serotonin. The presence of hypertension and high-normal blood pressure in obese children was most significantly affected by vitamin D deficiency and increased BMI-SDS. CONCLUSIONS: Dysregulation of vitamin D and serotonin can pose a risk of the onset and development of hypertension in obese children; therefore, their optimization together with reducing body weight may improve the long-term cardiovascular health of these children.

• Klíčová slova
• Children, Hypertension, Obesity, Serotonin, Vitamin D,
• MeSH
• ambulantní monitorování krevního tlaku MeSH
• dítě MeSH
• hypertenze * epidemiologie   MeSH
• index tělesné hmotnosti MeSH
• inzulin MeSH
• inzulinová rezistence * MeSH
• lidé MeSH
• nedostatek vitaminu D * MeSH
• obezita dětí a dospívajících * komplikace   epidemiologie   MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• serotonin MeSH
• vitamin D MeSH
• vitaminy MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inzulin MeSH
• serotonin MeSH
• vitamin D MeSH
• vitaminy MeSH

This study investigated 12-year blood lipid trajectories and whether these trajectories are modified by smoking and lipid lowering treatment in older Russians. To do so, we analysed data on 9,218 Russian West-Siberian Caucasians aged 45-69 years at baseline participating in the international HAPIEE cohort study. Mixed-effect multilevel models were used to estimate individual level lipid trajectories across the baseline and two follow-up examinations (16,445 separate measurements over 12 years). In all age groups, we observed a reduction in serum total cholesterol (TC), LDL-C and non-HDL-C over time even after adjusting for sex, statin treatment, hypertension, diabetes, social factors and mortality (P<0.01). In contrast, serum triglyceride (TG) values increased over time in younger age groups, reached a plateau and decreased in older age groups (> 60 years at baseline). In smokers, TC, LDL-C, non-HDL-C and TG decreased less markedly than in non-smokers, while HDL-C decreased more rapidly while the LDL-C/HDL-C ratio increased. In subjects treated with lipid-lowering drugs, TC, LDL-C and non-HDL-C decreased more markedly and HDL-C less markedly than in untreated subjects while TG and LDL-C/HDL-C remained stable or increased in treatment naïve subjects. We conclude, that in this ageing population we observed marked changes in blood lipids over a 12 year follow up, with decreasing trajectories of TC, LDL-C and non-HDL-C and mixed trajectories of TG. The findings suggest that monitoring of age-related trajectories in blood lipids may improve prediction of CVD risk beyond single measurements.

• MeSH
• HDL-cholesterol krev   MeSH
• kouření krev   epidemiologie   MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy * krev   MeSH
• longitudinální studie MeSH
• městské obyvatelstvo MeSH
• senioři MeSH
• stárnutí * krev   MeSH
• triglyceridy krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Rusko epidemiologie   MeSH
• Názvy látek
• HDL-cholesterol MeSH
• LDL-cholesterol MeSH
• lipidy * MeSH
• triglyceridy MeSH