Glucose Metabolism Disorders Research Articles

Evaluation of Maternal Factors Affecting Postpartum Insulin Resistance Markers in Mothers with Gestational Diabetes—A Case–Control Study

Background: Gestational diabetes mellitus (GDM) is defined by an insufficient insulin response to counteract the insulin resistance (IR) that arises from the physiological adaptations associated with pregnancy. However, the pathophysiology of IR is complex and unclear, as it encompasses elements such as epigenetics, environmental factors, modifiable lifestyle factors, and psychosocial factors. Aim: The objective of this study was to evaluate the influence of GDM and other maternal factors on IR markers in comparison to mothers with normal glucose tolerance during pregnancy in the first week postpartum. Material and Methods: The study population comprised 70 participants, including mothers with gestational diabetes who were treated with a diet and physical activity (GDM G1), with insulin (GDM G2), and a control group of healthy mothers without gestational diabetes (non-GDM). A series of statistical techniques were employed to facilitate the comparison of data between the study groups, with the objective of identifying potential associations with maternal factors. A taxonomic analysis was conducted using the following factors: classification by study group, a history of hypothyroidism in the maternal medical interview, and maternal gestational weight gain, which were identified as the best-fitting predictors. Results: The analysis resulted in the identification of four clusters of patients. Comparison of the insulin resistance markers between mothers assigned to the abovementioned clusters showed differences in the incidence of excessive weight loss and in the results of glucose screening tests during pregnancy. Also, differences concerning fasting glucose levels in the first and second/third trimesters of pregnancy and glucose levels at 1 h post-OGTT were found. For the clusters, the results of the HOMA-IR and the QUICKI did not show any differences in the first week after delivery (p > 0.05). HbA1c results varied significantly. Conclusions: Degree of glucose metabolism disorders, hypothyroidism, and weight gain in pregnancy influence maternal insulin resistance markers in the first week postpartum. Additionally, gestational weight fluctuation has a significant influence on the outcome of pregnancy, particularly with regard to fetal growth and, consequently, the infant’s birth weight and adipose tissue accumulation.

Abstract 4147634: Important Role of Prediabetes in Stroke Patients including ESUS

Stroke including ESUS is one of the common causes of disability and death worldwide. Furthermore, diabetes mellitus and prediabetes are among the main risk factors for cerebrovascular events. If the criteria for apparent diabetes mellitus is not met, a glucose metabolism disorder may still exist. Prediabetes can be present as impaired fasting glucose (IFG), impaired glucose tolerance or an increased, but not yet diabetic, HbA1c. To determine the frequency of diabetes mellitus (DM) and prediabetes mellitus (PDM) in patients with cardiovascular events, we analyzed the aspects of prediabetes in a stroke population of one of the largest stroke centers in Germany and collected the data in a prospective manner over 6 months. Among 714 included patients, 163 (30.8%) suffered a cryptogenic Stroke, including 98 (19%) ESUS. 185 (26%) TIA, 209 (39%) cardioembolic, 110 (21%) atherosclerotic, 40 (8%) lacunar and 7 (1%) other specific strokes were registered. >50% had a diabetic or prediabetic metabolic state, among which, the highest proportion was seen in lacunar strokes, followed by atherosclerotic infarctions. >80% of lacunar, >70% of atherosclerotic infarctions, 60% of ESUS, 50% of cardioembolic infarctions indicate DM or PDM. Both PDM and DM show a positive correlation with age. PDM is most common in 75-84y old patients. In the male population, PDM is most prevalent in the oldest patients (<85y) at >50%, and least prevalent in the youngest patients (<65y) at 15%. In this age group, women show a significantly higher frequency of DM and PDM. The highest number of female patients with glucose metabolism disorders is seen in the age group of 66-74y at >40%. In the oldest patient group, relatively speaking, more than twice as many men are affected by glucose metabolism disorders as women (52% vs. 24%). In summary the largest relative proportion of prediabetics and diabetics is seen at 80% among the lacunar infarction group and the second largest proportion at 70% among those with atherosclerotic infarctions. Among ESUS and cryptogenic stroke patients show a proportion of over 60% with impaired glucose tolerance. PD presents a positive correlation with increasing age, just like other risk factors. 40% of the 75-84-year-olds have DM or PDM. Therefore, diabetogenic micro- and macroangiopathies could be a major contributing factor to the causes of stroke.

Association of METS-IR index with Type 2 Diabetes: A cross-sectional analysis of national health and nutrition examination survey data from 2009 to 2018.

With rising global diabetes prevalence, precise early identification and management of diabetes risk are critical research areas. The metabolic score for insulin resistance (METS-IR), a novel non-insulin-based tool, is gaining attention for quantifying insulin resistance using multiple metabolic parameters. Despite its potential in predicting diabetes and its precursors, evidence on its specific relationship with diabetes is limited, especially in large-scale population validation and mechanistic exploration. This study aims to analyze the association between METS-IR and type 2 diabetes (T2DM) in American adults. We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) data from 2009 to 2018. Participants aged 20 years and above were included, excluding individuals with missing data on BMI, fasting blood glucose, high-density lipoprotein cholesterol glycated hemoglobin and diabetes status. Logistic regression analysis, subgroup analysis, and restricted cubic spline analysis were used to assess the association between METS-IR and T2DM, controlling for potential confounding factors. After adjusting for age, gender, race, education level, smoking status, drinking habits, depression, physical activity, hypertension, and hyperlipidemia, we found a positive association between METS-IR and the risk of T2DM. Specifically, each unit increase in METS-IR was associated with a 7% increase in the risk of T2DM (OR = 1.07, 95% CI: 1.06, 1.08). Subgroup analysis showed that the association between METS-IR and T2DM incidence was significantly positive in the highest quartile group, particularly among Mexican Americans over 40 years old and those diagnosed with depression, hypertension, or hyperlipidemia. Our study revealed a significant positive association between METS-IR and the prevalence of T2DM, indicating that this relationship persists even after controlling for various confounding factors. Therefore, monitoring METS-IR may provide a valuable tool for the early identification of individuals at risk of glucose metabolism disorders. Further research should focus on the applicability of METS-IR in different populations and its potential impact on clinical practice.

Multi-omics reveals the beneficial effect of Scytosiphon lomentaria fucoidan on glucose and lipid metabolism disorders via regulation of the gut-liver axis in pregnant mice

Multi-omics reveals the beneficial effect of Scytosiphon lomentaria fucoidan on glucose and lipid metabolism disorders via regulation of the gut-liver axis in pregnant mice

Effectiveness of King's Theory of Goal Attainment in Blood Glucose Management for Newly Diagnosed Patients With Type 2 Diabetes: Randomized Controlled Trial.

Diabetes poses a significant public health challenge in China and globally, with the number of patients expected to reach 592 million by 2035, notably in Asia. In China alone, an estimated 140 million individuals are living with diabetes, and a significant portion is nonadherent to medications, underscoring the urgency of effective management strategies. Recognizing the necessity of early and comprehensive management for newly diagnosed patients with type 2 diabetes, this study leverages an online teach-back method and "Internet + Nursing" platform based on King's Theory of Goal Attainment. The approach aims to enhance glycemic control and reduce fear and misconceptions about the disease, addressing both the educational and emotional needs of the patients. The primary aim of this study was to assess the effectiveness of King's Goal Attainment Theory in the management of newly diagnosed patients with type 2 diabetes. This research sought to develop a collaborative model for blood glucose management, integrating the expertise and roles of physicians, nurses, and patients. The model is designed to enhance the synergy in health care provision, ensuring a comprehensive approach to diabetes management. In this study conducted at Changzhou Traditional Chinese Medicine Hospital between January 2022 and February 2023, eligible patients were randomized into a control group or an online feedback group. The control group received standard care, while the online feedback group participated in a King's Theory of Goal Attainment-based online teach-back program, enhanced by "Internet + Nursing" strategies. This included an interactive platform for goal planning, video content sharing, comprehension assessment, misconception correction, and patient-driven recaps of disease information. Health monitoring was facilitated through the "Internet + Nursing" platform. The study focused on comparing changes in glucose metabolism and emotional disorder symptoms between the groups to evaluate the intervention's effectiveness. Following a 24-week intervention, we observed significant differences in key metrics between the online feedback group and the control group, each comprising 60 participants. The online feedback group demonstrated significant reductions in fasting plasma glucose, 2-hour postprandial glucose, and hemoglobin A1c (P<.05). Additionally, there was a notable decrease in hypoglycemia-related anxiety and alexithymia within this group. Conversely, the control group maintained relatively higher values for these metrics at the same time point (P<.05). These findings underscore the efficacy of online feedback in managing glycemic control and reducing psychological distress associated with hypoglycemia. The online teaching-back method, guided by King's Theory of Goal Attainment, effectively enhances glycemic control, reducing fasting plasma glucose, 2-hour postprandial glucose, and hemoglobin A1c levels in newly diagnosed patients with type 2 diabetes. Simultaneously, it alleviates hypoglycemia-related anxiety and mitigates alexithymia. This approach merits widespread promotion and implementation in clinical settings. Chinese Clinical Trial Registry ChiCTR2400079547; https://www.chictr.org.cn/showproj.html?proj=208223.

The effect of Xerostomia in diabetes mellitus patients on the incidence of dry socket after tooth extraction: A literature review

Background: Diabetes Mellitus (DM) is a metabolic disorder caused by the absence of insulin hormone production or lack of response to insulin. Diabetes mellitus can cause complications such as caries, periodontal disease, and xerostomia. Xerostomia is associated with low salivary flow which can cause several additional complications. Objective: To determine the effect of xerostomia, a complication in patients with diabetes mellitus, on the incidence of dry sockets after tooth extraction. Method: The method used in this study is a Literature Review, which searches three different journal databases, using the search terms "xerostomia" OR "diabetes mellitus" AND "tooth extraction" OR "dry socket." Results: It shows that there is an effect between the occurrence of xerostomia in patients with diabetes mellitus and the incidence of dry sockets after tooth extraction. Discussion: In patients with diabetes mellitus, saliva production can decrease due to nerve and blood vessel damage caused by glucose metabolism disorders in the body. This can reduce the quality and increase the viscosity of saliva, making the wound-healing process after tooth extraction more difficult. Xerostomia in patients with diabetes mellitus can worsen the dry socket condition because of the lack of moisture in the oral cavity, which can affect the blood clotting process after tooth extraction. If the blood clot dislodges, it can cause a dry socket in xerostomia patients. Conclusion: Dry socket in diabetic patients with xerostomia is thought to be due to low saliva production which interferes with wound healing after tooth extraction.

Effects of Zeaxanthin on the Insulin Resistance and Gut Microbiota of High-Fat-Diet-Induced Obese Mice

Obesity-induced insulin resistance (IR) can precipitate metabolic disorders such as diabetes. Zeaxanthin, a crucial member of the carotenoid family, has been found to mitigate the damage caused by obesity. However, reports on the effects of zeaxanthin on obesity-induced IR are lacking. Our objective was to examine the metabolic regulatory impacts of zeaxanthin on mice subjected to a high-fat diet (HFD) that triggered IR and to explore their influence on gut microbiota regulation. This study constructed a mouse model of metabolic dysfunction caused by lipid-rich nutritional patterns to investigate physiological and biochemical indices, liver pathway expression, and the intestinal microbiota. The mechanisms by which zeaxanthin improved both IR and glucose metabolic disorders were elucidated. The results demonstrate that zeaxanthin effectively suppressed obesity. The fasting blood glucose, area under curve of oral glucose tolerance test and insulin tolerance test, and homeostatic model assessment–insulin resistance (HOMA-IR) indices in the HFDZEA group decreased by 14.9%, 25.2%, 28.9%, and 29.8%. Additionally, zeaxanthin improved the lipid metabolism and alleviated damage to the liver and pancreas while also activating the PI3K/Akt pathway, regulating hepatic gluconeogenesis and the glycogen metabolism. The number of OTUs in the HFDZEA group increased by 29.04%. Zeaxanthin improved the structure and profile of the gastrointestinal microbiome and enhanced its diversity, increasing probiotics abundance, decreasing pathogen abundance, and thereby ameliorating the dysbiosis of enteric microbial communities in rodents with obesity resulting from excessive fat consumption. The outcomes of our analysis provide a rational basis for advancing zeaxanthin-based nutritional products.

Effects of Different Photoperiods on Peripheral 5-Hydroxytryptamine Metabolism, Breast Muscle Glucose Metabolism, and Myopathies in Broilers.

Background: There is a close relationship between breast muscle glucose metabolism, peripheral 5-hydroxytryptamine (5-HT), and myopathies in animals. Here, this study aimed to investigate the effects of different photoperiods on peripheral 5-HT metabolism, white striping (WS), and wooden breast (WB) in broilers. Methods: A total of 216 healthy 5-day-old (d) Arbor Acres (AA) male broilers were randomly assigned to 12L:12D, 18L:6D, and 24L:0D photoperiods for 4 weeks. Results: Compared with the 12L:12D photoperiod, we found the WB score in broilers was significantly increased in the 18L:6D and 24L:0D photoperiod at week 4 (p < 0.05). Muscle glycogen was significantly reduced (p < 0.05) and glycolysis was promoted in the breast muscles of broilers under the 18L:6D and 24L:0D photoperiods at week 2 and 4. Peripheral 5-HT concentrations, the mRNA expression of tryptophan hydroxylase 1 (TPH1) and serotonin transporter (SERT) in the cecal mucosa, and 5-hydroxytryptamine receptor 2A (5-HTR2A) mRNA expression in the breast muscle of broilers significantly up-regulated in the 18L:6D and 24L:0D photoperiod at week 2 and 4 (p < 0.05). Conclusions: Our findings revealed that extending the photoperiod improved the breast muscle growth rate, but up-regulated 5-HT synthesis and secretion to higher peripheral 5-HT, induced breast muscle glucose metabolism disorder, and increased WB incidence rates in broilers.

Tip60-mediated Rheb acetylation links palmitic acid with mTORC1 activation and insulin resistance.

Excess dietary intake of saturated fatty acids (SFAs) induces glucose intolerance and metabolic disorders. In contrast, unsaturated fatty acids (UFAs) elicit beneficial effects on insulin sensitivity. However, it remains elusive how SFAs and UFAs signal differentially toward insulin signaling to influence glucose homeostasis. Here, using a croaker model, we report that dietary palmitic acid (PA), but not oleic acid or linoleic acid, leads to dysregulation of mTORC1, which provokes systemic insulin resistance. Mechanistically, we show that PA profoundly elevates acetyl-CoA derived from mitochondrial fatty acid β oxidation to intensify Tip60-mediated Rheb acetylation, which triggers mTORC1 activation by promoting the interaction between Rheb and FKBPs. Subsequently, hyperactivation of mTORC1 enhances IRS1 serine phosphorylation and inhibits TFEB-mediated IRS1 transcription, inducing impairment of insulin signaling. Collectively, our results reveal a conserved molecular insight into the mechanism by which Tip60-mediated Rheb acetylation induces mTORC1 activation and insulin resistance under the PA condition, which may provide therapeutic avenues to intervene in the development of T2D.

Low-calorie, high-protein diets, regardless of protein source, improve glucose metabolism and cardiometabolic profiles in subjects with prediabetes or type 2 diabetes and overweight or obesity.

The aim was to study the effect of two low-calorie, high-protein (HP) diets, with most of the protein coming from animal or plant sources, on glycaemic and other cardiometabolic outcomes in subjects with overweight or obesity and glucose metabolism disorders. A total of 117 participants aged >18 years with body mass index over 27.5 kg/m2 and prediabetes or type 2 diabetes mellitus (T2DM) were randomized to one of two HP low-calorie diets (35% of total calories from protein), in which 75% of the protein was from either plant-based sources (HPP) or animal sources (HPA). For both diets, 30% and 35% of the total calories were from fat and carbohydrates, respectively. The dietary intervention lasted 6 months. Both diets improved body composition to a similar extent, including weight loss (-8.05 ± 5.12 kg for the HPA diet and -7.70 ± 5.47 kg for the HPP diet at 6 months) and fat mass, mainly visceral fat. Both diets had a similar beneficial effect on glucose metabolism, including fasting glucose, insulin, homeostasis model assessment of insulin resistance index and glycated haemoglobin. Other biochemical parameters, including lipid profiles, liver enzymes, adipokines and inflammatory biomarkers, similarly improved in both groups. Fasting incretins, mainly glucagon-like peptide 1, decreased significantly in both groups, and this effect correlated with weight loss. Low-calorie HP diets improved body composition, glucose metabolism and other cardiometabolic outcomes, regardless of protein source (either animal or plant sources), in outpatients with prediabetes or T2DM. The clinical trial was registered in ClinicalTrials.gov (identifier: NCT05456347) https://clinicaltrials.gov/study/NCT05456347?term=NCT05456347&rank=1.

Effects of Different Photoperiods on Growth Performance, Glucose Metabolism, Acetylcholine, and Its Relative Acetylcholine Receptor Modulation in Broiler Chickens.

Photoperiods are crucial environmental factors in the growth and health of modern intensive broiler chicken production. To date, the effects of different photoperiods on glucose metabolism, acetylcholine (ACh), and its relative acetylcholine receptor modulation in broilers remain elusive. Herein, we aimed to identify the effects of different photoperiods on regulating glucose metabolism, ACh, nicotinic acetylcholine receptor alpha 4 (α4 nAChR) mRNA, and M3 muscarinic acetylcholine receptor (M3 mAChR) modulation in broilers. A total of 216 healthy 5-day-old Arbor Acres (AA) male broilers was randomly assigned to 12L:12D, 18L:6D, and 24L:0D photoperiods for 4 weeks. The results show that, compared with the 12L:12D photoperiod, the 18L:6D and 24L:0D photoperiods significantly increase the average daily gain (ADG) and average daily feed intake (ADFI) of broilers (p < 0.05). However, the feed efficiency (FE) of broilers significantly decreased in the 18L:6D and 24L:0D photoperiods (p < 0.05). Moreover, compared with the 12L:12D photoperiod, the ACh concentrations and α4 nAChR mRNA expression levels in the hypothalamus and medulla oblongata of broilers significantly increased (p < 0.05); M3 mAChR mRNA expression levels in cecum significantly reduced in the 18L:6D photoperiod and the 24L:0D photoperiod (p < 0.05). Compared with the 12L:12D photoperiod, the serum glucose (GLU), serum insulin (INS), serum triglyceride (TG) levels, and homeostasis model assessment of insulin resistance (HOMA-IR) of broilers significantly enhanced in the 18L:6D and 24L:0D photoperiods (p < 0.05). Our results indicate that extending the photoperiod can promote the growth rate, ACh expression, and α4 nAChR mRNA expression of broilers while reducing the feed efficiency, inhibiting M3 mAChR mRNA expression, and inducing glucose metabolism disorders in broilers.

Metabolic and Immune Parameters in Pregnant Women with Impaired Glucose Metabolism-A Pilot Study.

Gestational diabetes mellitus (GDM) is a public health problem with increasing prevalence. Analyses of metabolic and immune profiles have great potential for discovering new markers and mechanisms related to the development of GDM. We monitored 61 pregnant women during the first and third trimesters of pregnancy, including 13 pregnant women with GDM, 14 pregnant women with elevated glucose in the first trimester and 34 healthy pregnant women. A number of metabolic and immunological parameters were measured, including glucose, insulin, lipid status, fatty acids, lymphocyte profile, adiponectin, IL-6, IL-10 and TNF-a. A higher number of T-helper lymphocytes and a higher ratio of helper/cytotoxic lymphocytes was found in the control group in the first trimester of pregnancy. Pregnant women whose glucose threshold values were measured in the first trimester, but who did not develop GDM, showed a higher percentage of neutrophils and a lower percentage of lymphocytes in the third trimester. Differences in polyunsaturated fatty acids levels were observed between healthy pregnant women and those with glucose metabolism disorders in the first trimester of pregnancy. The results of this pilot study demonstrate that there are differences in the profiles of T lymphocytes, NK cells and polyunsaturated fatty acids between the examined groups of pregnant women, which can serve as a direction for future research.

Moderate-intensity continuous training and high-intensity interval training alleviate glycolipid metabolism through modulation of gut microbiota and their metabolite SCFAs in diabetic rats

Glucose and lipid metabolism disorders are typical of diabetic patients and are important factors leading to macrovascular and microvascular complications. The aim of this study was to understand the effects of different exercises on glycolipid metabolism in diabetic rats and the role of gut flora in metabolic maintenance. We measured glycolipid metabolic indices and short-chain fatty acids (SCFAs) content and sequenced and analyzed gut microbes after 8 weeks of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) programs in type 2 diabetic rats(T2DM). We found that Enterococcaceae, Enterococcus, Subdoligranulum, Kurthia, Bacillales, and Planococcaceae may be key bacterial taxa related to T2DM and that both programs of exercise regulated the intestinal flora of rats with T2DM, improved their glycolipid metabolism, increased the abundance of SCFA-producing intestinal bacteria, and it was found that the PWY-5676 and P163-PWY pathways which are closely related to production of SCFAs were significantly upregulated in the exercise groups. Notably, MICT appeared to be more effective than HIIT in increasing the homogeneity of rat intestinal flora, enriching species, and increasing acetic acid and butyric acid content. These results suggest that exercise improves glycolipid metabolism in diabetic rats, which may be attributed to alterations in the structure of their intestinal flora.

Liver damage in patients hospitalized with acute decompensated heart failure, depending on the degree of glucose metabolism disorder

Aim. To study the frequency of cardiohepatic syndrome and steatosis by the value of controlled attenuation parameter (CAP), fibrosis, and their combination, depending on the degree of glucose metabolism disorder in patients with acute decompensated heart failure (ADHF).Materials and methods. The study included 280 patients (53% men, average age 70.1 ± 10.8 years) with ADHF: 72.5% of patients had a history of arterial hypertension, 60% of patients had coronary heart disease. The HbA1c test was performed in all patients to assess the status of glucose metabolism. The patients were divided into groups depending on the results obtained: at HbA1c values &lt; 5.7%, patients were included in the group without glucose metabolism disorders, at HbA1c 5.7–6.4% – in the prediabetes group, at HbA1c ≥ 6.5% – in the type 2 diabetes group. All patients underwent a standard physical examination at admission and at discharge. Clinical and comprehensive assessments of congestion were performed – NT-proBNP, lung ultrasound, liver fibroscan with CAP, and bioelectrical impedance analysis of body composition.Results. The frequency of glucose metabolism disorders in patients hospitalized with ADHF was 57.5% (n = 161), while prediabetes was detected in 17.1% (n = 48) and type 2 diabetes – in 40.4% (n = 113) of patients. We revealed significantly higher incidence of steatosis by CAP value (69 vs. 42%, p &lt; 0.001), fibrosis (80 vs. 64%, p &lt; 0.001), and their combination (59 vs. 30%, p &lt; 0.001), as well as cardiohepatic syndrome (87 vs. 61%, p &lt; 0.001) in patients with ADHF and glucose metabolism disorders compared to individuals with ADHF without glucose metabolism disorders, respectively. The group of ADHF patients with glucose metabolism disorders and a combination of steatosis / fibrosis was characterized by more pronounced manifestations of metabolic syndrome, impaired kidney and liver function, and more pronounced manifestations (both clinical and laboratory) of congestion.Conclusion. In patients with ADHF with glucose metabolism disorders, liver function test and liver fibroscan with CAP allow for identifying the most severe group of patients with a combination of steatosis/fibrosis and pronounced congestion.

Research Progress on the Mechanism for Improving Glucose and Lipid Metabolism Disorders Using Phenolic Acid Components from Medicinal and Edible Homologous Plants.

Glucose and lipid metabolism disorders are the core pathological mechanism of a variety of metabolic diseases, and the incidence of related diseases is increasing year by year, which seriously threatens human life and health. Traditional Chinese medicine with medicinal and edible properties refers to Chinese medicinal resources that have both medicinal and edible characteristics. Due to its safety and its health-promoting and medicinal functions, traditional Chinese medicine has received increasing attention in the development of functional health foods. Phenolic acids are important secondary metabolites that are ubiquitous in medicinal and edible homologous plants, and the regulation of glycolipid metabolism is an important activity and plays a key role in many diseases. In this paper, we focus on the alleviation of glycolipid disorders using MEHH phenolic acids, which regulate glucose metabolism and lipid metabolism, improve insulin resistance, inhibit inflammatory responses, alleviate oxidative stress, and regulate intestinal flora; additionally, we summarize the mechanism in order to provide a reference for MEHH phenolic acids in the treatment of glycolipid metabolism diseases.

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.

Unveiling the impact of dietary components on tropomyosin-induced anaphylaxis: Analysis from the perspective of intestinal barrier

There exists a strong correlation between diets and the increased incidence of food allergy. However, the precise mechanism underlying the impact of dietary fat, sucrose, or inulin on tropomyosin (TM)-induced anaphylaxis remains unclear. Therefore, the murine model of TM-induced food allergy fed with a high-fat, high-sucrose, high-dietary-fiber, or control diet was used to explore the mechanism. The high-sucrose diet was found to result in glucose and lipid metabolism disorders, as well as heightened allergic reactions characterized by decreased specific IgG2a levels and increased levels of specific IgE, specific IgG1, IL-4, peritoneal albumin, histamine, and mast cell degranulation. The aggravating impact of a high-fat diet on allergic reactions was weaker than that of a high-sucrose diet. It was attributed to the destruction of the intestinal mucus layer, the decreased expression of zona occludens 1 and occludin, and the increased release of IL-25 and IL-33. Meanwhile, a high sucrose intake led to dysbiosis of intestinal microbiota, and increased the abundance of Roseburia and norank_f_Oscillospiraceae, contributing to a further impairment of intestinal barrier function. Additionally, inulin intake significantly reduced the level of specific IgG1 and peritoneal albumin due to its protective effect on the intestinal barrier. To sum up, a better understanding of the relationship between diet and immune responses will be crucial for developing effective strategies for managing TM-induced food allergy.

The role of metabolic disorders in the development of atherosclerosis.

Atherosclerosis is a major risk factor for cardiovascular disease (CVD), which is the leading cause of death worldwide. Atherosclerosis is initiated by endothelial activation, followed by a cascade of events (accumulation of lipids, fibrous elements, and calcification) triggering vasoconstriction and activation of inflammatory pathways. This review focuses on the various stages in the development of atherosclerosis, ranging from endothelial dysfunction to plaque rupture. In addition, disorders of lipid, glucose and amino acid metabolism in atherosclerosis are considered here. The key pathological stages of metabolism disruption and their role in atherosclerosis are considered in detail which may be helpful for the more better understanding of atherosclerosis pathogenesis. Finally, some therapeutic approaches aimed at modulating lipid metabolism will also be presented which show the therapeutic targets (enzymes and transport proteins) which modulation can prevent further deterioration of patients symptoms.

7626 Endocrine Adverse Reactions Of Tyrosine Kinase Inhibitors In Combination With Immune Checkpoint Inhibitors: A Retrospective Analysis Using The US FDA Adverse Event Reporting System

Abstract Disclosure: W. Shao: None. D. Lu: None. K. Yang: None. Y. Gao: None. J. Zhang: None. Y. Zhang: None. Background: Tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI) have been recognized to cause multiple endocrine adverse reactions (EARs). However, the combination therapy-associated EARs is still unclear. We aimed to evaluate the clinical characteristics and prognosis of EARs induced by TKI, ICI and TKI+ICI therapy. Methods: Using the US FDA Adverse Event Reporting System, 938464 cases of all adverse events, adult patients, related to the three types of treatments from January 2001 to September 2023 were identified. A total of 22275 cases were EARs and divided into TKI (n=9181), ICI (n=11363) and TKI+ICI group (n=1731). Results: The incidence of EARs was the highest in TKI+ICI group (9.1%), followed by ICI (7.7%), and TKI group (1.2%) (P &amp;lt; 0.05). Among patients with EARs, the proportions of female and Asian patients were significantly greater in TKI+ICI group than in the other groups (P&amp;lt;0.05 for all). TKI+ICI group had a larger proportion of elderly patients compared with TKI group. The most common type of EARs in TKI+ICI group was thyroid dysfunction (TD) (67.5%), followed by glucose metabolism disorder (GMD) (14.0%). Compared with TKI group, TKI+ICI group displayed a higher risk of TD (OR 3.247, 95% CI [2.849-3.701]), pituitary dysfunction (PD) (OR 6.199, 95% CI [4.534-8.474]), and primary adrenal insufficiency (PAI) (OR 4.178, 95% CI [3.470-5.031]), while the risk of GMD was lower (OR 0.136, 95% CI [0.115-0.161]). Compared with ICI group, an increasing trend of TD (OR 2.640, 95% CI [2.328-2.995]) was found in TKI+ICI group, while a lower risk of GMD (OR 0.388, 95% CI [0.328-0.459]) and PD (OR 0.312, 95% CI [0.255-0.383]) was observed in TKI+ICI group. Hypothyroidism and diabetes mellitus were the main types of TD and GMD in all three groups. Patients with polyendocrine glands involvement accounted for the largest proportion in ICI group (11.4%), followed by TKI +ICI (7.9%), and TKI group (2.3%) (P&amp;lt;0.05). In TKI+ICI group, elderly patients, Asians, melanoma patients were more likely to experience multi-glandular EARs. In terms of prognosis, TKI+ICI group presented a higher risk of hospitalization compared to TKI (OR 2.201, 95% CI [1.943-2.492]) and ICI group (OR 1.282, 95%CI [1.139-1.442]). However, the mortality risk of TKI+ICI group was significantly lower (OR 0.717, 95% CI [0.588-0.874]) than TKI group, and there was no significant difference compared to ICI group. Moreover, there was no difference in mortality between patients with polyendocrine and single endocrine gland involvement. Conclusions: EARs were more common in TKI+ICI therapy. The distribution of EARs in different glands varied among combination therapy and monotherapy. Combination therapy associated EARs did not increase the risk of mortality. Key words: Tyrosine kinase inhibitors, Immune checkpoint inhibitors, Combination therapy, Endocrine adverse reactions, Prognosis Presentation: 6/3/2024

Network pharmacology analysis revealed the mechanism and active compounds of jiao tai wan in the treatment of type 2 diabetes mellitus via SRC/PI3K/AKT signaling

Ethnopharmacological relevanceJiao-tai-wan (JTW) is a traditional Chinese herbal prescription, exerts its therapeutic effects on type 2 diabetes mellitus (T2DM). However, its mechanisms and active components remain unclear. Aim of the studyTo investigate the therapeutic mechanisms of JTW in treating type 2 diabetes mellitus (T2DM), focusing on identifying active components, their targets, and validating efficacy through SRC/PI3K/AKT signaling pathway modulation in vitro and in vivo. Materials and methodsActive ingredients were retrieved from the Traditional Chinese Medicine System Pharmacology (TCMSP) and Comprehensive Traditional Chinese Medicine Database (TCMID). Targets for these components were identified using the ChemMapper database based on 3D structural similarity. T2DM-related genes were sourced from the DisGeNET and Gene Expression Omnibus (GEO) databases. Protein-protein interaction (PPI) analysis and functional enrichment analysis were conducted to construct a pathway network of “herbs-active ingredients-candidate targets”, identifying core molecular mechanisms and key active ingredients. SwissDock was used for molecular docking to predict ligands for candidate targets. The diabetic models were established using C57BL/6 mice and human liver HepG2 cell lines. Their Effectiveness and key molecules were verified through biochemical detection and immunoblotting. ResultsTotal 30 active compounds, 597 active ingredient targets, 9631 T2DM-related genes, and 521 overlapping candidate targets were found for JTW on T2DM. Go enrichment indicated the core pathways enriched on insulin and glucose metabolism. The auto-docking demonstrated SRC has potential binds to ingredients of JTW. In vivo, JTW can reduce blood glucose, and blood lipid levels, and HOMA-IR, and increase HOMA-ISI levels in T2DM mice with reduced ALT, AST, MDA levels and increased SOD levels. Meanwhile, decreased phosphorylation of SRC, along with increased levels of phosphorylated PI3K, PI3K, and phosphorylated AKT, were observed. HE staining of liver tissues further confirmed that JTW administration improved liver morphology, reducing inflammation and necrosis. In vitro, JTW significantly ameliorates upstream dysregulation by reducing SRC phosphorylation while enhancing phosphorylated PI3K, PI3K, and AKT phosphorylation levels. ConclusionJTW may alleviate glucose, insulin resistance, and lipid metabolism disorders by the SRC/PI3K/AKT signaling pathway, that provide a novel view of potential active compounds and essential targets in treating T2DM.