Carbohydrate Metabolism Disorders Research Articles

The role and function of metformin in women’s reproductive health: From pre-pregnancy preparation to breastfeeding

Disorders of carbohydrate metabolism not only reduce the quality of life of patients of reproductive age due to violations of the regularity of menstruation, anovulation and other clinical manifestations, but also affect the stages of pregnancy planning, affect the course of pregnancy and play an important role in the postpartum period. In overweight women, the presence of insulin resistance (IR), as well as existing disorders of carbohydrate metabolism, a conscious approach to pregnancy planning with maintaining targets before and throughout pregnancy is extremely important. The particular importance of a responsible approach is necessary due to the fact that glycemic disorders in both hyperand hypoglycemia are associated with risks on the part of the patient and the unborn child. Infertility, miscarriage, the risk of preeclampsia and eclampsia, as well as a high risk of birth injury (in relation to both mother and child) due to the peculiarities of childbirth with a large fetus are common among patients with impaired carbohydrate metabolism. Among all disorders of carbohydrate metabolism in patients of reproductive age, the most common are such as prediabetes, gestational diabetes mellitus, type 2 diabetes mellitus, all of which are associated with IR. Polycystic ovary syndrome, one of the main pathogenetic links of which is also IR, can be outlined separately. The use of metformin as a drug aimed at reducing IR is pathogenetically justified in such situations, however, despite the evidence of the safety of metformin presented by a large number of studies, there are no unified recommendations on dosage, timing and duration of metformin administration.

Modern aspects of therapy of metabolic associated liver disease in patients with type 2 diabetes mellitus

Metabolic associated fatty liver disease (MAFLD) is currently the most common liver disease. The main risk factors for its development are poor nutrition, sedentary lifestyle and obesity. MAFLD is associated with various cardiometabolic conditions – lipid metabolism disorders, cardiovascular pathology and carbohydrate metabolism disorders. The association of MAFLD and type 2 diabetes mellitus (DM) is common among patients, since these diseases have a common pathogenesis link – insulin resistance. The combination of these diseases has a mutual negative effect on each other and increases the risks of cardiovascular diseases, hospitalizations, as well as the risks of liver fibrosis progression. Therefore, the detection of MAFLD and its treatment in type 2 DM are extremely important to improve the patient’s prognosis. Diagnostics of MAFLD includes laboratory and instrumental research methods. The “gold standard” of diagnostics is considered to be liver biopsy, but due to the fact that this method is invasive, it is rarely used and only for differential diagnostics of MAFLD with other liver pathologies. The most accessible instrumental method for detecting liver steatosis is ultrasound. Treatment of MAFLD primarily involves lifestyle changes (rational nutrition with limitation of simple carbohydrates and animal fats, adequate physical activity) and weight loss. Also, hypoglycemic drugs used to treat type 2 diabetes (metformin, pioglitazone, glucagon-like peptide-1 agonists) can have a certain positive effect on MAFLD. Essential phospholipids, which have membrane-stabilizing, antioxidant and antifibrotic effects, are also an important component of MAFLD treatment. A number of domestic and foreign studies have shown the high efficiency of Essential Phospholipids both in relation to biochemical parameters in patients with a combination of type 2 diabetes and MAFLD, and in relation to ultrasound signs, improving the function and structure of the liver in MAFLD, as well as slowing the progression of liver fibrosis.

Prevention of iron deficiency conditions in obese children

Background. Due to the progressive increase in childhood obesity, the effect of iron levels in the body on carbohydrate and lipid metabolism disorders and the relationship between these conditions are actively studied. It is proven that obesity in children is often associated with dysregulation of iron metabolism. The correlation between the body mass index and iron deficiency (ID) in children and adolescents was reported. Therefore, implementing preventive measures to correct the iron deficiency state (IDS), including the enrichment of the diet with foods containing easily digestible iron, is relevant and can be considered as one of the principles of an integrated approach to the treatment of obesity in childhood. Aim. To evaluate the effectiveness of dietary supplements "Kidz Tasty iron" for IDS prevention in obese children. Materials and methods. Thirty children aged 7–14 with exogenous constitutional obesity were followed up, 14 (47%) females and 16 (53%) males. All patients received a dietary supplement (DS), "Kidz Tasty iron," 10 mL once daily with meals according to the label for 1 month. The follow-up included data on signs and symptoms, medical history, evaluation of anthropometric data, evaluation of current nutrition status with the software "Optimal Nutrition 5.0", bioimpedance analysis of body composition, questionnaire on the assessment of ID symptoms and quality of life, general hematology and blood chemistry tests, validated for childhood. Results. The diets of obese children in the study had low iron content (33.3% of patients), which justifies the need for additional iron supplementation. While taking the dietary supplement "Kidz Tasty Iron," there was a positive clinical trend: decreased symptoms related to ID and clinical signs of ID, improved overall well-being, and increased quality of life. The improvement of the body composition of the studied children was represented by preservation and an increase (20% of patients) in the active cell mass in the studied children. Laboratory tests of iron metabolism improved in 9 children (30%). Most children reported the good organoleptic properties of the product. Adherence to the DS was 96.7%. Conclusion. The study results show the "Kidz Tasty iron" dietary supplement to be tolerable, safe, and effective, supporting its use in the complex therapy of children and adolescents with obesity, including for IDS prevention.

Personalized management of hepatic glycogen storage disorders: The role of continuous glucose monitoring.

Glycogen storage disorders (GSD), inherent disorders of carbohydrate metabolism, feature hypoglycemia as a hallmark. Normoglycemia and glucose monitoring are pivotal in disease management. Conventional glucometer-based monitoring may overlook hypoglycemic trends. This study assesses glycemic control in Asian Indian GSD children using continuous glucose monitoring (CGM) and its role in facilitating dietary adjustments. A pre-post study enrolled molecularly confirmed GSDI, GSDIII, GSDVI, and GSDIX patients for baseline dietary compliance and CGM-based glycemic status evaluation. Hypoglycemic patients were stratified into diet-compliant and diet-noncompliant groups. Noncompliant patients received dietary reinforcement; compliant individuals underwent dietary adjustments. Repeat CGM (rCGM) was performed 6 weeks to 6 months postadjustments. Clinical and metabolic parameters were re-evaluated at 6 months. Of the 20 patients assessed at baseline, 11 were diet compliant. Six among these exhibited hypoglycemia, prompting diet adjustments. Among nine noncompliant patients, eight experienced hypoglycemia and received diet reinforcement. rCGM in 10 patients (five GSDI, three GSDIII, and two GSDIXc) showed a significant reduction in hypoglycemia duration in all. An improvement in height and body mass index was observed in all GSDI and GSDIII patients. Triglyceride levels, raised at baseline in two GSDI and one GSDIII, showed a substantial decline in one GSDI patient. Hepatic transaminase levels decreased in both GSDIXc patients. Plasma lactate levels decreased in all GSDI patients. CGM is an efficacious adjunct in the personalized management of hepatic GSD patients, in the Asian Indian population. The study also underscores the need for long-term follow-up to determine the role of glycemic management in growth, general well-being, and metabolic control in the GSD subtypes.

The interrelation of cardiometabolic risk factors and metabolic dysfunction-associated steatotic liver disease subtypes

Introduction. Metabolic dysfunction-associated steatotic liver disease is one of the leading causes of cirrhosis, liver cancer and extrahepatic complications. The number and various combinations of cardiometabolic risk factors, as well as the severity of liver steatosis, can affect the aggressiveness and prognosis of the disease. The article presents the results of own studies aimed at determining the prognostic significance of risk factors (individual and in different combinations) and steatometry.Objective. To determine the influence of individual cardiometabolic factors, their number and various combinations on the aggressiveness and prognosis of metabolic dysfunction-associated steatotic liver disease; to assess the prognostic value of steatometry for the disease.Material and methods. The examination results (steatometry, blood biochemistry tests, abdominal ultrasound) of patients diagnosed with metabolic dysfunction-associated steatotic liver disease were retrospectively analyzed. Statistical analysis: Student's t-test, Pearson's χ2-test, odds ratio, relative risk, Fisher's φ-test, ROC-analysis.Results. 146 patients were included. Cohort characteristics: average age 49.3 years, 84 men (57.5%). Aggressive forms (steatohepatitis, advanced steatosis) were associated with arterial hypertension, carbohydrate metabolism disorders (the most significant is insulin resistance), dyslipidemia, hyperuricemia. The severity of liver steatosis was less in patients who received therapy for lipid metabolism disorders comparing with those who didn’t. The presence of three or more cardiometabolic risk factors in a patient increased the risk of steatohepatitis and advanced steatosis. The combination of arterial hypertension and hyperuricemia significantly increased the risk of steatohepatitis. Advanced hepatic steatosis (≥310 dB/m2 by steatometry) was reliably associated with steatohepatitis.Conclusion. Individual risk factors, their number and combinations, contribute differently to the development of aggressive forms of the disease. Hyperuricemia should be considered as an additional cardiometabolic risk factor. Steatometry is capable of identifying advanced hepatic steatosis, being a risk factor for the development of steatohepatitis, which allows us to recommend it for the early diagnosis of metabolic dysfunction-associated steatotic liver disease.

GDF-15 and mtDNA Deletions Are Useful Biomarkers of Mitochondrial Dysfunction in Insulin Resistance and PCOS.

There is no literature available about the growth differentiation factor-15 (GDF-15) biomarker in combination with mitochondrial DNA (mtDNA) deletions in insulin resistance (IR), and polycystic ovary syndrome (PCOS); however, it would be useful to achieve optimal metabolic status and improve pregnancy success. In this study, the role of GDF-15 and mtDNA deletions as biomarkers in the pathogenesis of IR and PCOS was investigated. In our study, 81 female patients who were treated for IR and/or PCOS and 41 healthy controls were included. GDF-15 levels in patients showed a marked increase compared to controls. Elevated GDF-15 levels were found in 12 patients; all of them had a BMI > 25 kg/m2, which is associated with reactive hyperinsulinemia. The presence of mitochondrial dysfunction was mainly observed in the IR-only subgroup. The increase in plasma levels of GDF-15 and the prevalence of mtDNA deletions is directly proportional to body mass index. The more marked metabolic abnormalities required more intensive drug therapy with a parallel increase in plasma GDF-15 levels. Elevated levels of GDF-15 and the presence of mitochondrial DNA deletions may be a consequence of carbohydrate metabolism disorders in patients and thus a predictor of the process of accelerated aging.

The Assessment of Anthropometric Measures and Changes in Selected Biochemical Parameters in Obese Children in Relation to Blood Lead Level.

Our paper draws attention to the impact of lead (Pb) on the specificity of obesity development in children exposed to environmental pollution. An advantage of this paper is the homogeneous study group comprising children of identical age from a single geographic region. Moreover, while the influence of environmental toxins on adults has been extensively explored, this study delves into pediatric populations, which have yet to receive comprehensive scrutiny within the scientific literature. Initially, a group of 136 obese children (the research program lasted three consecutive years: 2016, 2017, and 2018) living in the north-western region of Poland, from whom biochemical tests and auxological data were obtained, were enrolled for analysis. Blood lead levels (BLLs) were determined in 115 children. The age of the children ranged from 7.1 to 10.4 years. The body mass index (BMI) of children averaged 21.5 ± 2.2. The results showed that a large proportion of the participants had BLLs above the threshold for Pb. BLLs ≤ 5 µg/dL (considered safe for children and pregnant women) were found in over 70% of the participants, with BLLs in the range of 5.01-10.00 µg/dL in over 26% of the children, and concentrations > 10 µg/dL (considered toxic threshold for adults) in nearly 2% of the children. The results of our research revealed a positive association between BLLs and average systolic and diastolic blood pressure in the studied children. Moreover, we found a negative correlation between BLLs and absolute fat tissue content and triglyceride concentration. Among the included biochemical factors, only insulin demonstrated a statistically significant relationship with fat mass. This result suggests that early carbohydrate metabolism disorders in overweight children involve decreased peripheral tissue insulin sensitivity. Lead exposure may significantly contribute to the development of hypertension, insulin resistance, and glucose metabolism disorders in overweight and obese children. It is essential to implement multidirectional actions to increase awareness of the harmful effects of xenobiotic exposure, including lead, in order to prevent early-life exposure.

Individually Perceived Parameters of Residential Infrastructure and Their Relationship with Cardiovascular Risk Factors

In modern medicine, studies devoted to the assessment of the parameters of residential infrastructure and the population’s attitude towards them have become quite large-scale. Objectives: The aim of the study was to establish associations between individually perceived parameters of residential infrastructure and the main modifiable cardiovascular risk factors (hypertension, obesity, lipid and carbohydrate metabolism disorders) in one of the subjects of the Russian Federation. Methods: The epidemiological study “Study of the influence of social factors on chronic non-communicable diseases” started in 2015 and ended in 2023. The sample was formed by using the stratification method based on the assignment to a medical organization. The study included 1598 respondents aged 35 to 70 years (491 rural residents). The study of infrastructure parameters was conducted based on the subjective opinions of respondents using the neighborhood environment walkability scale (NEWS) questionnaire, divided into eight scales. Logistic regression analysis was used to identify associations between infrastructure parameters and cardiovascular risk factors; the odds ratio (OR) and 95% confidence interval were evaluated. Results: Individually perceived infrastructure parameters of the scale B, reflecting the accessibility of infrastructure facilities, were associated with hypertension [OR = 1.33], obesity [OR = 1.40], and abdominal obesity [OR = 1.59]. Elements of the social infrastructure of the scale C, describing the streets in the residential area, increased the likelihood of developing obesity [OR = 1.42] and visceral obesity [OR = 1.43]. The characteristics of the residential area, represented by the scale D that evaluates pedestrian infrastructure, were associated with all major cardiovascular risk factors (hypertension [OR = 1.65], obesity [OR = 1.62] and abdominal obesity [OR = 1.82], and disorders of lipid [OR = 1.41] and carbohydrate metabolism [OR = 1.44]). Conclusion: Social factors represented by various aspects of infrastructure have become important criteria for determining cardiovascular health. Environmental conditions affect cardiovascular risk factors through behavioral patterns that shape the respondent’s lifestyle. Interventions in urban planning—increasing accessibility to infrastructure facilities for the population, developing a pedestrian-friendly urban environment, improving physical activity resources in areas, planning recreation areas, and landscaping—can become the most important concept for the prevention of cardiovascular diseases.

Type 3c diabetes mellitus: what are we dealing with? Review

The authors presented updated data on the term «type 3 diabetes mellitus», its modern classification, pathophysiological mechanisms of development and features of treatment, its definitions, epidemiology and modern classification based on the recommendations of the American Diabetes Association. Definitions and epidemiological features of acute pancreatitis and its most frequent complications, including 3c type diabetes have been described. Statistical data were presented on the risk of developing complications of acute pancreatitis in the form of carbohydrate metabolism disorders. Historical prerequisites of fatal complications of acute pancreatitis in the form of hyperglycemic states were also described. The pathophysiological mechanisms of the development of type 3c diabetes, namely local and systemic inflammation, loss of islet tissue of the pancreas, dysregulation of the insulin­­incretin axis, autoimmune destruction of β­cells of the pancreas, etc. were highlighted in detail. The role of genetic factors in the development of diabetes against the background of acute pancreatitis is described. Currently there are no standardized unified criteria of type 3c diabetes, thus the main and additional diagnostic criteria according to the different authors have been analyzed in detail. The differential characteristics and features of the diagnosis of diabetes mellitus by type and peculiarities of the diagnosis of type 1, 2 and 3c diabetes mellitus have been presented. The discussion on the glycemic target goals for patients with type 3c diabetes and the need for screening and prevention of carbohydrate metabolism disorders in patients with acute pancreatitis has been outlined. The authors provided current recommendations for the treatment of type 3c diabetes and discussed the possibilities of the use of insulin in the basis/bolus mode to achieve compensation of carbohydrate metabolism. The necessity to compensate pancreas exocrine insufficiency to improve the assimilation of fats and fat‑soluble vitamins has been emphasized.

8462 Synergistic Outcomes Of hCG And GLP1-RA Combination Therapy: Improved Body Composition And Carbohydrate Metabolism

Abstract Disclosure: F. Comite: None. K. O'Malley: None. Objective: Precision medicine prevents and reverses diseases of aging by way of systematic analysis of body composition and extensive blood biomarkers. Andropause, the age-related reduction of free testosterone (FT) in males, elicits symptoms primarily of muscle loss, decreased libido, and diminished energy. Exogenous testosterone therapy (TTx) subsequently increases lean body mass (LBM) and improves both libido and energy levels in affected males. More recently, stimulation of endogenous testosterone from the testes, human Chorionic Gonadotropin (hCG) has emerged as a compelling physiologic alternative to TTx. Common comorbidities to andropause are DMII and/or obesity. Recent literature surrounds the use of GLP-1 receptor agonists to improve insulin sensitivity in these disorders of carbohydrate metabolism. A primary benefit secondary to GLP-1 use is reduction of fat mass; however, concerns of this monotherapy surround loss of muscle.[1] Remarkably, when treated adjunctly with GLP-1s, hCG therapy significantly mitigates muscle loss while maintaining optimal carbohydrate biomarkers. The efficacy and benefits of hormonal optimization through hCG therapy simultaneous to GLP-1 intervention were investigated. Methods: In this retrospective analysis, a cohort of 20 males ≥30 years of age were reviewed at baseline timepoints and 18 months post treatment-initiation. Participants underwent biweekly hCG and weekly GLP-1 subcutaneous injections. Exclusion criteria restricted use of alternative GLP-1/GIP combination medication. Paired T-Tests were used to determine a relationship between LBM, FT, percent body fat (PBF), fasting glucose (FG), fasting insulin (FI), and HbA1c at each timepoint. Results: Body composition analysis as shown via bioelectrical impedance proved baseline PBF (mean=24.60) significantly reduced post-treatment (p<0.05, mean=18.08) for all participants. In addition, relevant carbohydrate metabolic biomarkers FG, FI, and HbA1c provided significant reductions (p<0.05). Initial FT (mean=67.76) and LBM (mean=150.36) increased significantly at follow-up (p<0.05) with values of 167.55 and 154.91, respectively. Discussion: Using metrics of precision medicine, our interpretation reveals a promising combination therapy for males experiencing andropause. The novel use of hCG to optimize FT levels enhances muscle, while simultaneously, fat loss and reversal of harmful carbohydrate metabolic markers resultant from GLP-1 therapy are achieved. Muscle loss due to overall weight loss is thus ameliorated. Our findings merit further investigation of the magnitude of downstream improvements, particularly in energy and libido.

The relationship between iron metabolism markers and parameters of carbohydrate and lipid metabolism in patients with overweight and obesity

Background: Hyperferritinemia associated with obesity and insulin resistance is a link between the components of the metabolic syndrome and a possible triggering factor in the pathogenesis of carbohydrate metabolism disorders and dyslipidemia.Aim: To establish possible relationships between ferrokinetic parameters, parameters of lipid and carbohydrate metabolism in overweight and obese patients, and to analyze the possibility of using iron metabolism parameters (ferritin and serum iron) as predictors of carbohydrate metabolism disorders in this cohort of patients.Material and Methods. The study included 52 overweight or obese patients. In the course of the study, patients were stratified into groups depending on the presence of carbohydrate metabolism disorders (CMD), and depending on the state of iron metabolism. Among all patients included in the study, an assessment of anthropometric data, a study of glycated hemoglobin, a standard glucose tolerance test with 75 g of glucose, a study of hematological parameters, as well as biochemical parameters of iron metabolism – the concentration of serum iron, transferrin and ferritin, was carried out.Results. Patients with CMD – impaired glucose tolerance or impaired fasting glycaemia – had significantly higher serum ferritin levels than obese patients without CMD (p = 0.019). In persons with a high level of ferritin, CMD developed significantly more often than in patients with a ferritin content in the range below the 75th percentile (χ2 = 5.278, p = 0.022). According to the ROC analysis, ferritin showed a rather high sensitivity – 75%, and specificity – 84.4% at a diagnostic threshold of 126.65 ng/ml (area under the curve = 0.738; p = 0.016) in the diagnosis of prediabetes (IGT/IFG) in overweight and obese individuals.Conclusion. High concentrations of iron and ferritin are positively associated with CMD, with ferritin being a promising predictor of prediabetes and type 2 diabetes mellitus.

A-328 Accuracy of the Glucose Test in the i-STAT® G Cartridge Using the i-STAT 1 System for Venous, Arterial and Capillary Whole Blood Specimens in Clinical Settings

Abstract Background Precise and accurate measurements of whole blood glucose levels are important for the diagnosis, monitoring and treatment of carbohydrate metabolism disorders, such as diabetes and hypoglycemia. This study demonstrates the accuracy of the glucose test in the i-STAT G cartridge with the i-STAT 1 System in arterial, venous, and capillary whole blood specimens in point of care or clinical laboratory settings. Methods The accuracy of the glucose test in the i-STAT G cartridge was assessed at external clinical sites in a method comparison study using whole blood specimens across the measurement range of 20 - 700 mg/dL. Specimens used in this study were venous, arterial, and capillary specimens prospectively collected under Institutional Review Board-approved informed consent or were leftover de-identified venous or arterial specimens. The study included venous whole blood samples from 164 adult subjects (≥ 18 years) and arterial whole blood samples from 173 adult subjects at 3 clinical sites, and capillary whole blood samples from 211 adult subject at 3 clinicals sites and 23 neonate subjects (birth to 28 days) at 2 clinical sites. For venous and arterial whole blood, samples were collected and tested in duplicate on the i-STAT G cartridge and on the i-STAT CHEM8+ cartridge (comparator). For capillary whole blood samples, adult fingerstick samples and neonate heel-stick samples were collected in capillary tubes and tested in singlicate on the i-STAT G cartridge and in singlicate on the epoc® Blood Analysis System (comparator). Passing-Bablok linear regression was performed for venous and arterial whole blood samples using the first replicate from the i-STAT G cartridge versus the mean result of the comparator, and for capillary whole blood samples (adult and neonate combined) using the singlicate result from the i-STAT G cartridge versus the singlicate result of the comparator. Results Passing-Bablok regression of i-STAT G cartridge results versus the comparator was used to calculate slope and correlation coefficient (r). Adult venous whole blood results had slope = 1.00 and r = 1.00, and adult arterial whole blood results had slope = 1.00 and r = 1.00. Adult and neonate capillary whole blood results had slope = 1.00 and r = 1.00. Conclusions These results demonstrate that the i-STAT 1 System delivers accurate glucose test results within ∼2 minutes using the i-STAT G cartridge for venous, arterial and capillary whole blood samples for adult and neonate subjects across a glucose range of 20-700 mg/dL when tested by end-users in a point of care or clinical laboratory setting. This study was funded by Abbott Laboratories.

Bictegravir alters glucose tolerance in vivo and causes hepatic mitochondrial dysfunction

Growing evidence associates antiretroviral therapies containing integrase strand transfer inhibitors or tenofovir alafenamide (TAF) with increased weight gain and metabolic diseases, but the underlying mechanisms remain unclear. This study evaluated the impact of lamivudine, dolutegravir (DTG), bictegravir (BIC), tenofovir disoproxil fumarate, and TAF on metabolic alterations, and explored glucose homeostasis and mitochondrial stress as potential mechanisms. These pathways were analyzed both in vivo (C57BL/6J mice treated with the abovementioned drugs or vehicle for 16 weeks) and in vitro (in Hep3B cells). Mice treated with BIC exhibited higher glucose levels and a slower decrease during a glucose tolerance test. Functional enrichment analyses of livers from antiretroviral-treated mice revealed that only BIC altered the cellular response to insulin and induced a gluconeogenic-favoring profile, with Fgf21 playing a significant role. In vitro, BIC significantly reduced hepatocyte glucose uptake in a concentration-dependent manner, both under basal conditions and post-insulin stimulation, while the other drugs produced no significant changes. Hep3B cells treated with clinically relevant concentrations of BIC exhibited significant alterations in the mRNA expression of enzymes related to glucose metabolism. Both DTG and BIC reduced mitochondrial dehydrogenase activity, but only BIC increased reactive oxygen species, mitochondrial membrane potential, and cellular granularity, thereby indicating mitochondrial stress. BIC promoted mitochondrial dysfunction, modified carbohydrate metabolism and glucose consumption in hepatocytes, and altered glucose tolerance and gluconeogenesis regulation in mice. These findings suggest that BIC contributes to insulin resistance and diabetes in people living with HIV, warranting clinical studies to clarify its association with carbohydrate metabolism disorders.

Algorithms for evaluation of minimal cut sets

Objective:We propose a way to enhance the evaluation of minimal cut sets (MCSs) in biological systems modeled by Petri nets, by providing criteria and methodology for determining their optimality in disabling specific processes without affecting critical system components. Methods:This study concerns Petri nets to model biological systems and utilizes two primary approaches for MCS evaluation. First is the analyzing impact on t-invariants to identify structural dependencies. Second is assessing the impact on potentially starved transitions caused by the inactivity of specific MCSs. This approach deal with net dynamics. These methodologies aim to offer practical tools for assessing the quality and effectiveness of MCSs. Results:The proposed methodologies were applied to two case studies. In the first case, a cholesterol metabolism network was analyzed to investigate how local inflammation and oxidative stress, in conjunction with cholesterol imbalances, influence the progression of atherosclerosis. The MCSs were ranked, with the top sets presented, focusing on those that disabled the fewest number of t-invariants. In the second case, a carbohydrate metabolism disorder model was examined to understand its impact on atherosclerosis progression. The analysis aimed to identify MCSs that could inhibit the atherosclerosis process by targeting specific transitions. Both studies utilized the Holmes software for calculations, demonstrating the effectiveness of the proposed evaluation methodologies in ranking MCSs for practical biological applications. Conclusion:The algorithms proposed in this paper offer an analytical approach for evaluating the quality of MCSs in biological systems. By providing criteria for MCS optimality, these approaches have potential to enhance the utility of MCS analysis in systems biology, aiding in the understanding and manipulation of complex biological networks.Algorithm are implemented within Holmes software, an open-source project available at https://github.com/bszawulak/HolmesPN.

Correlation links in a risk model for carbohydrate metabolism disorders and cardiovascular disease in overweight patients

Correlation links in a risk model for carbohydrate metabolism disorders and cardiovascular disease in overweight patients

Lipid and carbohydrate metabolism disturbances in children with chronic hepatitis C

Aim. To study the state of lipid and carbohydrate metabolism, body composition, liver parenchyma structure in children with chronic hepatitis C (CHC).Materials and methods. 63 children with CHC examined at DNACIB in 2022–2023 (anthropometry, laboratory examination, bioimpedance analysis (BIA) of body composition, liver elastography with evaluation of steatosis).Results. Abnormalities of lipid metabolism were detected in 1/3 of children with CHC even with normal and low body mass index (BMI). Signs of insulin resistance (HOMAIR>3,2) were found in 54% of children with CHC. One third of patients with insulin resistance have liver steatosis, which significantly exceeds the frequency of steatosis registration among children without insulin resistance. There was a tendency for the frequency of insulin resistance to increase in proportion to the progression of the stage of liver fibrosis. No association between hepatitis virus genotype and disorders of lipid and carbohydrate metabolism was found.Conclusion. As a result of hepatitis C virus exposure in children with CHC, the risk of insulin resistance formation increases, which may be one of the pathogenetic mechanisms of liver steatosis development, increasing the risk of severe liver fibrosis formation and unfavorable outcome of the disease.

A specific serum lipid signature characterizes patients with glycogen storage disease type Ia

Glycogen storage disease type Ia (GSDIa) is a rare, inherited glucose-6-phosphatase-α (G6Pase-α) deficiency-induced carbohydrate metabolism disorder. Although hyperlipidemia is a hallmark of GSDI, the extent of lipid metabolism disruption remains incompletely understood. Lipidomic analysis was performed to characterize the serum lipidome in patients with GSDIa, by including age- and sex-matched healthy controls and age-matched hypercholesterolemic controls. Metabolic control and dietary information biochemical markers were obtained from patients with GSDIa. Patients with GSDIa showed higher total serum lysophosphatidylcholine (Fold Change, (FC) 2.2, P < 0.0001), acyl-acyl-phosphatidylcholine (FC 2.1, P < 0.0001), and ceramide (FC 2.4, P < 0.0001) levels and bile acid (FC 0.7, P < 0.001), acylcarnitines (FC 0.7, P < 0.001), and cholesterol esters (FC 1.0, P < 0.001) than those of healthy controls, and higher di- (FC 1.1, P < 0.0001; FC 0.9, P < 0.01) and triacylglycerol (FC 6.3, P < 0.0001; FC 3.9, P < 0.01) levels than those of healthy controls and hypercholesterolemic subjects. Both total cholesterol and triglyceride values correlated with Cer (d16:1/22:0), Cer (d18:1/20:0), Cer (d18:1/20:0(OH)), Cer (d18:1/22:0), Cer (d18:1/23:0), Cer (d18:1/24:1), Cer (d18:2/22:0), Cer (d18:2/24:1). Total cholesterol also correlated with Cer (d18:1/24:0), Cer (d18:2/20:0), HexCer (d16:1/22:0), HexCer (d18:1/18:0), and Hex2Cer (d18:1/20:0). Triglyceridelevels correlated with Cer (d18:0/24:1). Alanine aminotransferase values correlated with Cer (d18:0/22:0), insulin with Cer (d18:1/22:1) and Cer (d18:1/24:1), and HDL with hexosylceramide (HexCer) (d18:2/23:0). These results expand on the currently known involvement of lipid metabolism in GSDIa. Circulating Cer may allow for refined dietary assessment compared with traditional biomarkers. Because specific lipid species are relatively easy to assess, they represent potential novel biomarkers of GSDIa.

Assessment of the in vitro anti-diabetic activity with molecular dynamic simulations of limonoids isolated from Adalia lemon peels

Limonoids are important constituents of citrus that have a significant impact on promoting human health. Therefore, the primary focus of this research was to assess the overall limonoid content and isolate limonoids from Adalia lemon (Citrus limon L.) peels for their potential use as antioxidants and anti-diabetic agents. The levels of limonoid aglycones in the C. limon peel extract were quantified through a colorimetric assay, revealing a concentration of 16.53 ± 0.93 mg/L limonin equivalent. Furthermore, the total concentration of limonoid glucosides was determined to be 54.38 ± 1.02 mg/L. The study successfully identified five isolated limonoids, namely limonin, deacetylnomilin, nomilin, obacunone 17-O-β-D-glucopyranoside, and limonin 17-O-β-D-glucopyranoside, along with their respective yields. The efficacy of the limonoids-rich extract and the five isolated compounds was evaluated at three different concentrations (50, 100, and 200 µg/mL). It was found that both obacunone 17-O-β-D-glucopyranoside and limonin 17-O-β-D-glucopyranoside possessed the highest antioxidant, free radical scavenging, and anti-diabetic activities, followed by deacetylnomilin, and then the limonoids-rich extract. The molecular dynamic simulations were conducted to predict the behavior of the isolated compounds upon binding to the protein's active site, as well as their interaction and stability. The results revealed that limonin 17-O-β-D-glucopyranoside bound to the protein complex system exhibited a relatively more stable conformation than the Apo system. The analysis of Solvent Accessible Surface Area (SASA), in conjunction with the data obtained from Root-Mean-Square Deviation (RMSD), Root-Mean-Square Fluctuation (RMSF), and Radius of Gyration (ROG) computations, provided further evidence that the limonin 17-O-β-D-glucopyranoside complex system remained stable within the catalytic domain binding site of the human pancreatic alpha-amylase (HPA)-receptor. The research findings suggest that the limonoids found in Adalia lemon peels have the potential to be used as effective natural substances in creating innovative therapeutic treatments for conditions related to oxidative stress and disorders in carbohydrate metabolism.

Dysmetabolism of Peripheral Blood Monocytes in Type 1 Diabetes Mellitus.

The level of ROS (fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate) and lipid content (fluorescent lipophilic dye Nile Red) in the peripheral blood monocyte fraction from patients with type 1 diabetes mellitus and healthy volunteers were assessed by flow cytofluorimetry. The number of CD36+ monocytes was assessed using specific antibodies. In patients with type 1 diabetes mellitus, the levels of ROS and intracellular lipids in monocytes and the number of cells expressing CD36 fatty acid translocase were elevated. These results indicate metabolic changes in the peripheral blood cells of patients with carbohydrate metabolism disorders and can be considered as possible prognostic markers for the development of type 1 diabetes mellitus complications.

Subclinical Left Ventricular Dysfunction over Seven-Year Follow-Up in Type 2 Diabetes Patients without Cardiovascular Diseases.

Subclinical left ventricular dysfunction (LVD) is common in asymptomatic patients with type 2 diabetes (T2D). This study aimed to define long-term structural and functional disorders of the left ventricle (LV) myocardium over a 7-year follow-up in patients with T2D without cardiovascular diseases (CVD). Of the 120 patients with and without T2D of both sexes aged from 45 to 75 years (57.11 ± 7.9 years), included in the study in 2012-2013, 57 responded to the follow-up study. They were divided into two groups: one with T2D (n = 29), the other without it, the control (n = 28). All patients underwent transthoracic two-dimensional echocardiography with an assessment of standard indicators of systolic and diastolic cardiac function, global longitudinal strain (GLS), laboratory diagnostics of carbohydrate metabolism disorders markers, NT-proBNP, and CRP. The median follow-up duration was 7.2 [7.0-7.8] years. During the follow-up, a statistically significant increase in the incidence of diastolic dysfunction (DD) from 53% to 61% (p = 0.004) was found in the T2D group; no significant dynamics were noted in the control group (p = 0.48). The proportion of patients with reduced GLS (<-18%) increased in the T2D group (p = 0.036). A significant difference in the frequency of decreased GLS depending on presence of T2D was demonstrated. In conclusion, T2D is an independent risk factor for the worsening of subclinical left ventricular dysfunction in asymptomatic patients with T2D without CVD over 7-year follow-up.