Increased Odds of Metabolic Dysfunction-Associated Steatotic Liver Disease Are Linked to Reduced n-6, but Not n-3 Polyunsaturated Fatty Acids in Plasma.

The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) underscores the need for better understanding of its complex pathogenesis. Lipid accumulation in hepatocytes is among principal mechanisms contributing to MASLD development. While routine lipid parameters are well studied, the profile of circulating fatty acids in MASLD patients remains less explored. This study aimed to assess relative proportions of individual fatty acids in plasma of MASLD patients and to explore their associations with other biochemical markers of MASLD. Ninety-one patients and 48 healthy individuals were enrolled. The relative proportions of fatty acids in plasma were determined using gas chromatography with FID detection. Proportions of total n-6 polyunsaturated fatty acids (PUFAs) and linoleic acid (LA) in plasma were lower in MASLD patients (p = 0.001 and p = 0.004, respectively), with no differences observed in n-3 PUFAs. Total plasma n-6 PUFAs correlated negatively with body mass index, hepatic steatosis indices, triglyceride concentration and coronary risk index. Decreased prevalence of n-6 PUFAs in plasma was independently associated with higher odds of MASLD (OR = 0.769; CI: 0.611-0.968; p = 0.025). Our findings indicate an altered circulatory fatty acid distribution in MASLD, characterized by a reduced amount of n-6 PUFAs, particularly LA, which may have significant implications for the prevention and treatment of MASLD.

Differences in HDL Remodeling during Healthy Pregnancy and Pregnancy with Cardiometabolic Complications.

This study investigated the longitudinal trajectory of changes in antioxidative and anti-inflammatory high-density lipoprotein (HDL) components during healthy pregnancy and pregnancy with cardiometabolic complications. We recruited and longitudinally followed 84 women with healthy pregnancies and 46 pregnant women who developed cardiometabolic pregnancy complications (gestational diabetes mellitus and hypertensive disorders of pregnancy). Their general lipid profiles, oxidative stress status, inflammatory status, and antioxidative and anti-inflammatory HDL components were analyzed. The results of our study confirmed the expected trajectory for the routine lipid parameters. Our study results indicate more intensive oxidative stress and a higher level of inflammation in the group with complications compared with the control group. Sphingosine-1-phosphate (S1P) was significantly lower in the first trimester in the group with complications compared with the control group (p < 0.05). We did not find significant differences in the apolipoprotein A1 (Apo A1) concentrations in the first trimester between the control group and the group with complications, but in the second and third trimesters, the group with complications had significantly higher concentrations (p < 0.001, p < 0.05, respectively). The S1P, paraoxonase 1 (PON1), and serum amyloid A (SAA) concentrations were significantly lower in the group with complications in the first trimester. During the second trimester, only the SAA concentrations were identified as significantly lower in the group with complications compared with the control group, while in the third trimester, the PON1, apolipoprotein M (Apo M), and SAA concentrations were all significantly lower in the group with complications. Through a multivariate binary logistic regression analysis, the S1P concentration in the first trimester was distinguished as an HDL-associated marker independently associated with cardiometabolic pregnancy complications. In conclusion, our study results showed that HDL remodeling differs between healthy pregnancies and pregnancies with maternal cardiometabolic complications, with changed HDL composition and functionality consequently impacting its biological functionality in the latter case.

COVID-19 increases mortality in hemodialysis patients: exploring links with inflammation and telomere attrition.

BACKGROUND AND OBJECTIVE: An increased risk of mortality and hospitalization was consistently demonstrated in hemodialysis (HD) patients affected by pandemic coronavirus infection (COVID-19). In this study, we analyzed parameters that may impact mortality in COVID-19 HD patients, including neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP), COVID-19 disease status and telomere length in peripheral blood cells (TL). MATERIALS AND METHODS: A total of 130 chronic hemodialysis patients were enrolled and followed up for 18 months. Patients were categorized into groups based on their COVID-19 disease history and subsequent data about their survival status at the end of the study. Routine laboratory parameters were assessed using standard automated methods and TL was determined using the modified Cawthon method. Survival predictors were analyzed using Kaplan-Meier analysis. RESULTS: Deceased patients (30%) were older with higher body mass index (BMI), higher levels of LDH, NLR index, CRP and lower TL and lymphocytes count compared to survivors. Kaplan-Meier survival analysis showed six parameters were significant mortality predictors in the following order of significance: COVID-19 history, 2-years cardiovascular mortality risk score, NLR, TL, CRP, LDH. Using binary logistic regression analysis Summary risk score, a combination of these six parameters revealed as the best predictor of patient's survival in this group of parameters (log rank 25.4, p < 0.001). CONCLUSION: Compared to the general population, the mortality rate among HD patients persists at a higher level despite advancements in HD technology and patient care. The situation has been exacerbated by COVID-19, by significant increase in mortality rate among these patients.

Sex-Specific Associations between Thyroid Status, Inflammation and Hemostasis Biomarkers in Patients with Subacute Thyroiditis.

Background: Subacute thyroiditis (SAT) is characterized by profound inflammation and fluctuations in thyroid hormones which may affect the hemostasis balance. This study investigates sex-specific associations between thyroid status, inflammation and hemostasis biomarkers in SAT. Methods: We included 52 patients (40 women and 12 men) treated with non-steroidal anti-inflammatory drugs (NSAID) or methylprednisolone (MPS). Free thyroxine (fT4), thyroid stimulating hormone, C-reactive protein, complete blood count and routine hemostasis parameters were assessed. Results: Both men and women were in hyperthyroid state and had comparable levels of inflammatory biomarkers. A shortened activated partial thromboplastin time (aPTT) was observed in 16.7% of the men and 10% of the women (p = 0.562), and a shortened prothrombin time (PT) was observed in 33% of the men and 12.5% of the women (p = 0.094). In men, aPTT positively correlated with fT4 (r = 0.627; p < 0.05), while PT positively correlated with leukocyte-based inflammatory indices in women (p < 0.05). NSAID-treated patients had lower aPTTs and platelet counts than those treated with MPS (p < 0.05). Principal component analysis extracted "proinflammatory", "prothrombotic" and "antithrombotic" factors, but the "proinflammatory" factor was the independent predictor of elevated fT4 in women (OR = 2.705; p = 0.036). Conclusions: Our data demonstrated sex-specific associations of thyroid status and inflammatory biomarkers with hemostasis parameters in SAT. Routine hemostasis screening tests may help in monitoring the changes in the hemostasis system over the course of SAT.

The Effects of Pregestational Overweight and Obesity on Maternal Lipidome in Pregnancy: Implications for Newborns' Characteristics.

Obesity is an important risk factor for the development of pregnancy complications. We investigated the effects of pregestational overweight and obesity on maternal lipidome during pregnancy and on newborns' characteristics. The study encompassed 131 pregnant women, 99 with pre-pregnancy body mass index (BMI) < 25 kg/m2 and 32 with BMI ≥ 25 kg/m2. Maternal lipid status parameters, plasma markers of cholesterol synthesis and absorption and sphingolipids were determined in each trimester. Data on neonatal height, weight and APGAR scores were assessed. The results showed a higher prevalence (p < 0.05) of pregnancy and childbirth complications among the participants with elevated pregestational BMI. Levels of total cholesterol, HDL-cholesterol (p < 0.05) and LDL-cholesterol (p < 0.01) were significantly lower, and concentrations of triglycerides were higher (p < 0.05) in women with increased pre-gestational BMI. Lower concentrations of the cholesterol synthesis marker, desmosterol, in the 2nd trimester (p < 0.01) and the cholesterol absorption marker, campesterol, in each trimester (p < 0.01, p < 0.05, p < 0.01, respectively) were also found in this group. Markers of maternal cholesterol synthesis were in positive correlation with neonatal APGAR scores in the group of mothers with healthy pre-pregnancy weight but in negative correlation in the overweight/obese group. Our results indicate that gestational adaptations of maternal lipidome depend on her pregestational nutritional status and that such changes may affect neonatal outcomes.

Obesity and dyslipidemia in early life: Impact on cardiometabolic risk.

Childhood obesity with its growing prevalence worldwide presents one of the most important health challenges nowadays. Multiple mechanisms are involved in the development of this condition, as well as in its associations with various cardiometabolic complications, such as insulin resistance, diabetes, metabolic dysfunction-associated steatotic liver disease and cardiovascular diseases. Recent findings suggest that childhood obesity and associated dyslipidemia at least partly originate from epigenetic modifications that take place in the earliest periods of life, namely prenatal and perinatal periods. Hence, alterations of maternal metabolism could be fundamentally responsible for fetal and neonatal metabolic programming and consequently, for metabolic health of offspring in later life. In this paper, we will review recent findings on the associations among intrauterine and early postnatal exposure to undesirable modulators of metabolism, development of childhood obesity and later cardiometabolic complications. Special attention will be given to maternal dyslipidemia as a driven force for undesirable epigenetic modulations in offspring. In addition, newly proposed lipid biomarkers of increased cardiometabolic risk in obese children and adolescents will be analyzed, with respect to their predictive potential and clinical applicability.

The influence of Klotho protein and prooxidant-antioxidant balance combination on the mortality of HD patients.

PURPOSE: End-stage renal disease patients on chronic hemodialysis (HD) have a shortened life expectancy compared to the general population. The aim of this study was to evaluate a possible link between three new and emerging factors in renal pathophysiology: Klotho protein, telomere length in peripheral blood mononuclear cells (TL) and redox status parameters before HD (bHD) and after HD (aHD), and to test mortality prediction capability of these emerging parameters in a population of HD patients. METHODS: The study included 130 adult patients with average age 66 (54-72), on HD (3 times per week; 4-5 h per session). Klotho level, TL, routine laboratory parameters, dialysis adequacy and redox status parameters: advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), superoxide anion (O2.-), malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl group content (SHG), and superoxide dismutase (SOD) were determined. RESULTS: Klotho concentration was significantly higher aHD; 68.2 (22.6-152.9) vs. bHD 64.2 (25.5-119.8) (p = 0.027). The observed increase in TL was not statistically significant. AOPP, PAB, SHG, and SOD activity were significantly increased aHD (p > 0.001). The patients with the highest mortality risk score (MRS) had significantly higher PAB bHD (p = 0.002). Significantly lower O2.- (p < 0.001), SHG content (p = 0.072), and IMA (p = 0.002) aHD were found in patients with the lowest MRS values. Principal component analysis revealed redox balance-Klotho factor as a significant predictor of high mortality risk (p = 0.014). CONCLUSION: Decreased Klotho and TL attrition as well as redox status disturbance could be connected with higher mortality rate in HD patients.

Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk.

Oxidative stress is the consequence of an overproduction of reactive oxygen species (ROS) that exceeds the antioxidant defense mechanisms. Increased levels of ROS contribute to the development of cardiovascular disorders through oxidative damage to macromolecules, particularly by oxidation of plasma lipoproteins. One of the most prominent features of atherogenic dyslipidemia is plasma accumulation of small dense LDL (sdLDL) particles, characterized by an increased susceptibility to oxidation. Indeed, a considerable and diverse body of evidence from animal models and epidemiological studies was generated supporting oxidative modification of sdLDL particles as the earliest event in atherogenesis. Lipid peroxidation of LDL particles results in the formation of various bioactive species that contribute to the atherosclerotic process through different pathophysiological mechanisms, including foam cell formation, direct detrimental effects, and receptor-mediated activation of pro-inflammatory signaling pathways. In this paper, we will discuss recent data on the pathophysiological role of oxidative stress and atherogenic dyslipidemia and their interplay in the development of atherosclerosis. In addition, a special focus will be placed on the clinical applicability of novel, promising biomarkers of these processes.

Obesity and Dyslipidemia: A Review of Current Evidence.

PURPOSE OF REVIEW: Obesity is accompanied by atherogenic dyslipidemia, a specific lipid disorder characterized by both quantitative and qualitative changes of plasma lipoproteins. The main alterations in the lipid profile include hypertriglyceridemia, reduced high-density lipoprotein (HDL) cholesterol level, and elevated small dense low-density lipoprotein (LDL) particles. Epidemiological data show that obesity is more common in women and is a frequent risk factor for reproductive disorders, metabolic complications in pregnancy, and cardiometabolic disease later in life. The aim of this narrative review is to discuss recent advances in the research of dyslipidemia in obesity, with an emphasis on female-specific disorders and cardiometabolic risk. RECENT FINDINGS: The focus of current research on dyslipidemia in obesity is moving toward structurally and functionally modified plasma lipoproteins. Special attention is paid to the pro-atherogenic role of triglyceride-rich lipoproteins and their remnants. Introduction of advanced analytical techniques enabled identification of novel lipid biomarkers with potential clinical applications. In particular, proteomic and lipidomic studies have provided significant progress in the comprehensive research of HDL's alterations in obesity. Obesity-related dyslipidemia is a widespread metabolic disturbance in polycystic ovary syndrome patients and high-risk pregnancies, but is seldom evaluated with respect to its impact on future cardiometabolic health. Obesity and associated cardiometabolic diseases require a more depth insight into the quality of lipoprotein particles. Further application of omics-based techniques would enable a more comprehensive evaluation of dyslipidemia in order to reduce an excessive cardiovascular risk attributable to increased body weight. However, more studies on obesity-related female reproductive disorders are needed for this approach to be adopted in daily clinical practice.

Cholesterol Metabolic Profiling of HDL in Women with Late-Onset Preeclampsia.

A specific feature of dyslipidemia in pregnancy is increased high-density lipoprotein (HDL) cholesterol concentration, which is probably associated with maternal endothelium protection. However, preeclampsia is most often associated with low HDL cholesterol, and the mechanisms behind this change are scarcely explored. We aimed to investigate changes in HDL metabolism in risky pregnancies and those complicated by late-onset preeclampsia. We analyze cholesterol synthesis (cholesterol precursors: desmosterol, 7-dehydrocholesterol, and lathosterol) and absorption markers (phytosterols: campesterol and ß-sitosterol) within HDL particles (NCSHDL), the activities of principal modulators of HDL cholesterol's content, and major HDL functional proteins levels in mid and late pregnancy. On the basis of the pregnancy outcome, participants were classified into the risk group (RG) (70 women) and the preeclampsia group (PG) (20 women). HDL cholesterol was lower in PG in the second trimester compared to RG (p < 0.05) and followed by lower levels of cholesterol absorption markers (p < 0.001 for campesterolHDL and p < 0.05 for ß-sitosterolHDL). Lowering of HDL cholesterol between trimesters in RG (p < 0.05) was accompanied by a decrease in HDL phytosterol content (p < 0.001), apolipoprotein A-I (apoA-I) concentration (p < 0.05), and paraoxonase 1 (PON1) (p < 0.001), lecithin-cholesterol acyltransferase (LCAT) (p < 0.05), and cholesterol ester transfer protein (CETP) activities (p < 0.05). These longitudinal changes were absent in PG. Development of late-onset preeclampsia is preceded by the appearance of lower HDL cholesterol and NCSHDL in the second trimester. We propose that reduced capacity for intestinal HDL synthesis, decreased LCAT activity, and impaired capacity for HDL-mediated cholesterol efflux could be the contributing mechanisms resulting in lower HDL cholesterol.

HDL Subclasses and the Distribution of Paraoxonase-1 Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction.

The aim of this multicentric study was to assess the impacts of oxidative stress, inflammation, and the presence of small, dense, low-density lipoproteins (sdLDL) on the antioxidative function of high-density lipoprotein (HDL) subclasses and the distribution of paraoxonase-1 (PON1) activity within HDL in patients with ST-segment elevation acute myocardial infarction (STEMI). In 69 STEMI patients and 67 healthy control subjects, the lipoproteins' subclasses were separated using polyacrylamide gradient (3-31%) gel electrophoresis. The relative proportion of sdLDL and each HDL subclass was evaluated by measuring the areas under the peaks of densitometric scans. The distribution of the relative proportion of PON1 activity within the HDL subclasses (pPON1 within HDL) was estimated using the zymogram method. The STEMI patients had significantly lower proportions of HDL2a and HDL3a subclasses (p = 0.001 and p < 0.001, respectively) and lower pPON1 within HDL3b (p = 0.006), as well as higher proportions of HDL3b and HDL3c subclasses (p = 0.013 and p < 0.001, respectively) and higher pPON1 within HDL2 than the controls. Independent positive associations between sdLDL and pPON1 within HDL3a and between malondialdehyde (MDA) and pPON1 within HDL2b were shown in the STEMI group. The increased oxidative stress and increased proportion of sdLDL in STEMI are closely related to the compromised antioxidative function of small HDL3 particles and the altered pPON1 within HDL.

The Prospect of Genomic, Transcriptomic, Epigenetic and Metabolomic Biomarkers for The Personalized Prevention of Type 2 Diabetes and Cardiovascular Diseases.

Cardiometabolic diseases, such as type 2 diabetes mellitus (DM) and cardiovascular disease (CVD), are a great health concern. The strategies aimed to increase awareness and prevention, in conjunction with timely diagnosis and optimal management of these conditions, represent the main lines of action to improve life expectancy and quality. In recent years, the introduction of innovative therapies for the treatment of DM and CVD has provided new hope for high-risk patients. Yet, the implementation of preventive measures in achieving cardiometabolic health is far from successful and requires further improvement. The development of cardiometabolic disorders is a complex, multifactorial process involving several metabolic pathways as well as genetic and environmental factors. Decreasing cumulative exposure during the entire life course and timely recognition and targeting of potential riskenhancing factors could pave the way toward more successful prevention of cardiometabolic disorders. Nowadays, in the era of "omics" technologies, it is possible to identify novel biomarkers and therapeutic targets, which offers the possibility to apply an individualized approach for each patient. This review will discuss potential applications of genomic, transcriptomic, epigenetic and metabolomic biomarkers for the personalized prevention of cardiometabolic diseases.

The Role of Advanced Glycation End Products on Dyslipidemia.

Disorders of lipoprotein metabolism and glucose homeostasis are common consequences of insulin resistance and usually co-segregate in patients with metabolic syndrome and type 2 diabetes mellitus (DM). Insulin-resistant subjects are characterized by atherogenic dyslipidemia, a specific lipid pattern which includes hypertriglyceridemia, reduced high-density lipoprotein cholesterol level, and increased proportion of small, dense low-density lipoprotein (LDL). Chronic hyperglycemia favors the processes of non-enzymatic glycation, leading to the increased production of advanced glycation end products (AGEs). Apart from direct harmful effects, AGEs are also potent inducers of oxidative stress and inflammation. In addition, increased AGEs' production may induce further qualitative modifications of small, dense LDL particles, converting them to glycated LDLs. These particles are even more atherogenic and may confer an increased cardiovascular risk. In this narrative review, we summarize the available evidence of the pathophysiological role and clinical importance of circulating AGEs and glycated LDLs in patients with dyslipidemia, particularly those with DM and related complications. In addition, we discuss recent advances and the issues that should be improved regarding laboratory assessment of AGEs and glycated LDLs, as well as the possibilities for their therapeutic modulation.

Oxidative Stress and Inflammatory Biomarkers in Patients with Diabetic Foot.

Background and Objectives: Diabetic foot (DF) development is driven by complex interactions of hyperglycemia, inflammation, and oxidative stress (OS). We aimed to investigate OS and inflammatory biomarkers in patients with DF and their potential to improve early diagnosis and management of DF. Materials and Methods: The prooxidant−antioxidant balance (PAB), superoxide dismutase (SOD), total oxidative status (TOS), total sulfhydryl groups (SHG), routine biochemical parameters, and complete blood count were determined in 42 patients with type-2 DM, of which 23 patients had DF, while 19 patients were without DF complications. The neutrophils-to-lymphocyte ratio (NLR) was evaluated as a biomarker of inflammation. Results: Patients with DF had significantly higher (p < 0.05) PAB levels (170 ± 33.9 U/L) compared to those without DF complications (142 ± 31.3 U/L). In addition, patients with DF had significantly reduced SOD activities (p < 0.01). NLR values were significantly higher in the DF group (median: 2.8; interquartile range: 2.0−4.3) than in the group without DF (median: 1.4; interquartile range: 1.4−2.1; p < 0.01). A positive correlation was found between the PAB and NLR index (r = 0.449; p < 0.05). The diagnostic accuracy of both PAB (AUC = 0.741; p < 0.01) and NLR (AUC = 0.760; p < 0.01) was estimated as acceptable. Conclusions: In conclusion, the development of DF is associated with enhanced OS and inflammation processes. PAB and NLR could be useful non-invasive biomarkers of DF development.

Association of Adiponectin Receptors with Metabolic and Immune Homeostasis Parameters in Colorectal Cancer: In Silico Analysis and Observational Findings.

Adiponectin (ADIPOQ) as both a regulator of metabolic homeostasis and a protein involved in immune response might be of particular interest to contemporary laboratory medicine, especially in terms of minimally invasive diagnostics. The diverse roles of ADIPOQ with regard to the immune and metabolic aspects of colorectal carcinogenesis have been proposed. However, the expression of its receptors ADIPOR1 and ADIPOR2 is scarcely explored in peripheral blood mononuclear cells (PBMCs). Moreover, ADIPORs' relationships with the immune response mediator TNF-α have not been previously investigated in the PBMCs of CRC patients. This study used both in silico and observational case-control analyses with the aim of exploring the association of ADIPOR gene expression and ADIPOQ single nucleotide polymorphisms (SNPs) with the inflammatory marker TNF-α and lipid status parameters in patients with CRC. Publicly available transcriptomic datasets (GSE47756, GSE44076) obtained from analyses of monocytes and CRC tissue samples were employed for the in silico evaluation of ADIPORs' specific genetic traits. GSE47756 and GSE44076 datasets were processed with GSEA software to provide a genetic fingertip of different signaling pathways associated with ADIPORs' mRNA levels. The case-control aspect of the study included the PBMC samples of 73 patients diagnosed with CRC and 80 healthy volunteers. The PCR method was carried out for the PBMC gene expression analysis (ADIPOR1, ADIPOR2, TNF-α mRNA levels) and for the subjects' genotyping (ADIPOQ rs266729, ADIPOR1 rs7539542). GSEA showed significant associations of ADIPOR mRNA expression with gene sets related to metabolic and immune homeostasis in both datasets. The case-control study revealed the association of ADIPOR1 rs7539542 with reduced lipid status parameters in CRC. In addition, PBMC ADIPOR1 mRNA levels decreased in CRC (p < 0.001), whereas ADIPOR2 mRNA did not differ between the groups (p = 0.442). A reduction in PBMC TNF-α mRNA levels was noted in CRC (p < 0.05). Our results indicate that ADIPOR1 and ADIPOR2 play a significant role in the alteration of both metabolic and immune homeostasis during the progression of CRC. For the first time, ADIPOR1 is shown to be a specific receptor for mediating ADIPOQ's effects in the PBMCs of CRC patients.

Alteration in Redox Status and Lipoprotein Profile in COVID-19 Patients with Mild, Moderate, and Severe Pneumonia.

Background: Metabolic alterations, particularly disorders of lipoprotein metabolism in COVID-19, may affect the course and outcome of the disease. This study aims at evaluating the lipoprotein profile and redox status in SARS-CoV-2 infected patients with different pneumonia severity and their association with lethal outcomes. Methods: The prospective cohort study was performed on 98 COVID-19 patients with mild, moderate, and severe pneumonia. Lipid and inflammatory parameters, lipoprotein subclasses, and redox status biomarkers were determined at the study entry and after one week. Results: Compared to patients with mild and moderate pneumonia, severely ill patients had higher oxidised low-density lipoprotein (oxLDL) and malondialdehyde levels and lower high-density lipoprotein cholesterol (HDL-C) concentrations and paraoxonase 1 activity. Reduction in the proportion of large HDL 2a subclasses with a concomitant increase in the proportion of smallest HDL 3c and small dense LDL (sdLDL) particles was observed in patients with severe disease during the time. However, these changes were reversed in the mild and moderate groups. The results showed a positive association between changes in oxLDL and total antioxidative status. However, prooxidants and antioxidants in plasma were lower in patients with lethal outcomes. Conclusions: Increased levels of oxLDL and sdLDL particles may contribute to the severity of COVID-19. The role of oxidative stress should be clarified in further studies, mainly its association with lethal outcomes.

Effects of Gestational Diabetes Mellitus on Cholesterol Metabolism in Women with High-Risk Pregnancies: Possible Implications for Neonatal Outcome.

Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1−T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, ß-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of ß-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum ß-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn's size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM.

Glucose Metabolism Disorders: Challenges and Opportunities for Diagnosis and Treatment.

Alterations of glucose metabolism are recognized as one of the most important risk factors for the development and complications of cardiometabolic diseases [...].

Downregulation of mapk/mak/mrk overlapping kinase 1 in peripheral blood mononuclear cells of pediatric patients with type 1 diabetes mellitus.

Background: Type 1 diabetes mellitus (T1DM) is one of the most common endocrine diseases in children. T-cell autoreactivity toward b-cells is controlled by significant changes in metabolism of T cells. Mammalian target of rapamycin (mTOR) is an important intracellular regulator of metabolism and cell growth. MAPK/MAK/MRK overlapping kinase 1 (MOK1) is one of the less known regulators of mTOR. We sought to investigate if MOK1 and mTOR mRNA levels in peripheral blood mononuclear cells (PBMCs) of T1DM pediatric patients are different compared to healthy subjects. Methods: This study included 172 adolescents with T1DM and 36 healthy adolescent volunteers designated for control group (CG). MOK1 and mTOR mRNA levels were determined in PBMCs by qPCR. Results: T1DM patients have significant downregulation of MOK1 mRNA levels in PBMCs compared CG (P=0.018), while there was no significant difference in mTOR mRNA levels (P=0.891). Furthermore, in T1DM patients, MOK1 significantly correlated with age, triglycerides and mTOR, while mTOR correlated significantly with BMI and systolic blood pressure. Overweight T1DM subjects had significantly lower MOK1 (P=0.034) and mTOR (P=0.017) mRNA levels, together with significantly higher levels of systolic blood pressure (P<0.001), total cholesterol (P=0.001), LDL-cholesterol (P=0.001) and CRP (P<0.001). Multi - variate analysis showed that MOK1 was independently negatively associated with T1DM when adjusted for sex, age, HDL-C and CRP (OR=0.417 (95%CI: 0.175-0.997), p=0.049). Conclusions: Our study demonstrated for the first time that T1DM is associated with MOK1 downregulation. In addition, downregulation of both mTOR and MOK1 gene expressions was associated with cardiovascular risk factors in overweight T1DM patients.