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Background: Antiretroviral therapy (ART)‐associated metabolic abnormalities, including impairment of glucose metabolism, are prevalent in adults living with HIV. However, the prevalence and pathogenesis of impaired glucose metabolism in children and adolescents living with HIV, particularly in sub‐Saharan Africa, are not well characterized. We investigated the prevalence of impaired glucose metabolism among children and adolescents living with perinatally infected HIV in Ghana. Methods: In this multicentre, cross‐sectional study, we recruited participants from 10 paediatric antiretroviral treatment clinics from January to June 2022 in 10 facilities in Greater Accra and Eastern regions of Ghana. We determined impaired glucose metabolism in the study sample by assessing fasting blood sugar (FBS), insulin resistance as defined by the homeostatic model assessment for insulin resistance (HOMA‐IR) index and glycated haemoglobin (HbA1c) levels. The prevalence of impaired glucose metabolism using each criterion was stratified by age and sex. The phenotypic correlates of glucose metabolism markers were also assessed among age, sex, body mass index (BMI) and waist‐to‐hip ratio (WHR). Results: We analysed data from 393 children and adolescents living with HIV aged 6–18 years. A little over half (205/393 or 52.25%) of the children were female. The mean age of the participants was 11.60 years (SD = 3.50), with 122/393 (31.00%) aged 6–9 years, 207/393 (52.67%) aged 10–15 years, and 62/393 (15.78%) aged 16–18 years. The prevalence rates of glucose impairment in the study population were 15.52% [95% confidence interval (CI): 12.26–19.45], 22.39% (95% CI: 18.54–26.78), and 26.21% (95% CI: 22.10–30.78) using HbA1c, HOMA‐IR, and FBS criteria, respectively. Impaired glucose metabolism detected by FBS and HOMA‐IR was higher in the older age group, whereas the prevalence of abnormal HbA1c levels was highest among the youngest age group. Age and BMI were positively associated with FBS and HOMA‐IR (p < 0.001). However, there was negative correlation of WHR with HOMA‐IR (p < 0.01) and HbA1c (p = 0.01). Conclusion: The high prevalence of impaired glucose metabolism observed among the children and adolescents living with HIV in sub‐Saharan Africa is of concern as this could contribute to the development of metabolic syndrome in adulthood. [ABSTRACT FROM AUTHOR]

This study was to investigate the effect and possible mechanism of circadian rhythm change on the development of nonalcoholic fatty liver disease (NAFLD) in mice. A total of 80 male SPF-grade 4-week C57BL/6J mice were randomly divided into normal diet normal light/dark cycle (ND-LD) and high-fat diet all dark (HFD-DD) groups. Weight measurements were taken weekly, and after 24 weeks of intervention, 24 mice from both groups were randomly selected and analyzed. Additionally, the remaining mice in the HFD-DD group were divided into two groups: one group continued the high-fat all-dark treatment (HFD-DD-DD), and the other group was restored to normal light/dark cycle treatment (HFD-DD-LD). Mice were euthanized after a total of 48 weeks of intervention. Measurements were taken for each mouse including liver function serum indicators, liver tissue pathological sections, rhythm-related proteins, and determination of the gut microbiota community. The HFD induced NAFLD in mice, exhibiting symptoms such as obesity, lipid and glucose metabolism disorders, elevated liver enzymes, and decreased gut microbiota diversity. The composition of the gut microbiota was significantly different from that of the normal diet group, with a significant increase in the ratio of Firmicutes to Bacteroides. Restoration of normal light/dark cycles exacerbated the disorder of lipid metabolism, liver steatosis, and the expression of BMAL1 in mice and significantly reduced the diversity of gut microbiota. Circadian rhythm changes aggravate the development of NAFLD induced by a high-fat diet by affecting glucose metabolism, liver steatosis, and gut microbiota diversity. Restoration of normal circadian rhythm did not improve NAFLD. Our findings open up new avenues for the prevention, diagnosis, and treatment of NAFLD. • High-fat diet and circadian changes reduce gut microbiome richness and diversity. • HFD-DD (24th week) BMAL1 is higher than HFD-LD, indicating circadian influence. • HFD groups show elevated body weights, liver ratios, and abnormal liver structure. • HFD-DD-LD shows reduced gut microbiome richness compared to HFD-DD-DD. • Rhythm restoration didn't improve metabolism or steatosis in HFD-fed mice. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common systemic disorder related to endocrine disorders, affecting the fertility of women of childbearing age. It is associated with glucose and lipid metabolism disorders, altered gut microbiota, and insulin resistance. Modern treatments like pioglitazone, metformin, and spironolactone target specific symptoms of PCOS, while in Chinese medicine, moxibustion is a common treatment. This study explores moxibustion’s impact on PCOS by establishing a dehydroepiandrosterone (DHEA)-induced PCOS rat model. Thirty-six specific pathogen-free female Sprague-Dawley rats were divided into four groups: a normal control group (CTRL), a PCOS model group (PCOS), a moxibustion treatment group (MBT), and a metformin treatment group (MET). The MBT rats received moxibustion, and the MET rats underwent metformin gavage for two weeks. We evaluated ovarian tissue changes, serum testosterone, fasting blood glucose (FBG), and fasting insulin levels. Additionally, we calculated the insulin sensitivity index (ISI) and the homeostasis model assessment of insulin resistance index (HOMA-IR). We used 16S rDNA sequencing for assessing the gut microbiota, 1 H NMR spectroscopy for evaluating metabolic changes, and Spearman correlation analysis for investigating the associations between metabolites and gut microbiota composition. The results indicate that moxibustion therapy significantly ameliorated ovarian dysfunction and insulin resistance in DHEA-induced PCOS rats. We observed marked differences in the composition of gut microbiota and the spectrum of fecal metabolic products between CTRL and PCOS rats. Intriguingly, following moxibustion intervention, these differences were largely diminished, demonstrating the regulatory effect of moxibustion on gut microbiota. Specifically, moxibustion altered the gut microbiota by increasing the abundance of UCG-005 and Turicibacter, as well as decreasing the abundance of Desulfovibrio. Concurrently, we also noted that moxibustion promoted an increase in levels of short-chain fatty acids (including acetate, propionate, and butyrate) associated with the gut microbiota of PCOS rats, further emphasizing its positive impact on gut microbes. Additionally, moxibustion also exhibited effects in lowering FBG, testosterone, and fasting insulin levels, which are key biochemical indicators associated with PCOS and insulin resistance. Therefore, these findings suggest that moxibustion could alleviate DHEA-induced PCOS by regulating metabolic levels, restoring balance in gut microbiota, and modulating interactions between gut microbiota and host metabolites. [ABSTRACT FROM AUTHOR]

Hyperglycemia is correlated with worse in-hospital outcomes in acute infectious diseases such as coronavirus disease 2019 (COVID-19) and severe fever with thrombocytopenia syndrome (SFTS). This study assessed the relationship between fasting plasma glucose (FPG) levels and in-hospital mortality, disease type, and secondary infections among individuals with SFTS without preexisting diabetes. The clinical data and laboratory results upon admission of 560 patients with SFTS without preexisting diabetes meeting the inclusion criteria at Wuhan Union Hospital were collected. FPG levels in surviving patients with SFTS subjects were significantly lower than those in patients with SFTS who had died (P<0.0001). In multivariate Cox regression, high FPG level (≥11.1 mmol/L) was a risk factor independently associated with the in-hospital death of patients with SFTS without preexisting diabetes. Similarly, the FPG levels in general patients with SFTS were significantly lower than those in patients with severe SFTS (P<0.0001). Multivariate logistic regression identified high FPG level (7.0–11.1 mmol/L) as a risk factor independently associated with SFTS severity. While FPG levels were comparable between patients with SFTS with and without secondary infection (P = 0.5521), logistic regression analysis revealed that high FPG levels were not a risk factor for secondary infection in patients with SFTS without preexisting diabetes. High FPG level on admission was an independent predictor of in-hospital death and severe disease in individuals with SFTS without preexisting diabetes. FPG screening upon admission and glycemic control are effective methods for improving the prognosis of patients with SFTS. Author summary: Diabetes is a risk factor for a less favorable prognosis in patients with cancer or autoimmune diseases, but few studies have explored the association between fasting plasma glucose (FPG) levels and in-hospital mortality, disease type, and secondary infections among individuals with severe fever and thrombocytopenia syndrome (SFTS). Our study reveal that high FPG level on admission was an independent predictor of in-hospital death and severe disease in individuals with SFTS without preexisting diabetes. FPG screening upon admission and glycemic control are effective methods to assess the prognosis and disease type of patients with SFTS regardless of diabetes status, as most individuals with SFTS are prone to glucose metabolism disorders. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosteroneinduced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS. [ABSTRACT FROM AUTHOR]

Patients with inflammatory liver diseases, particularly alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease (MAFLD), have higher incidence of infections and mortality rate due to sepsis. The current focus in the development of drugs for MAFLD is the resolution of non-alcoholic steatohepatitis and prevention of progression to cirrhosis. In patients with cirrhosis or alcoholic hepatitis, sepsis is a major cause of death. As the metabolic center and a key immune tissue, liver is the guardian, modifier, and target of sepsis. Septic patients with liver dysfunction have the highest mortality rate compared with other organ dysfunctions. In addition to maintaining metabolic homeostasis, the liver produces and secretes hepatokines and acute phase proteins (APPs) essential in tissue protection, immunomodulation, and coagulation. Inflammatory liver diseases cause profound metabolic disorder and impairment of energy metabolism, liver regeneration, and production/secretion of APPs and hepatokines. Herein, the author reviews the roles of (1) disorders in the metabolism of glucose, fatty acids, ketone bodies, and amino acids as well as the clearance of ammonia and lactate in the pathogenesis of inflammatory liver diseases and sepsis; (2) cytokines/chemokines in inflammatory liver diseases and sepsis; (3) APPs and hepatokines in the protection against tissue injury and infections; and (4) major nuclear receptors/signaling pathways underlying the metabolic disorders and tissue injuries as well as the major drug targets for inflammatory liver diseases and sepsis. Approaches that focus on the liver dysfunction and regeneration will not only treat inflammatory liver diseases but also prevent the development of severe infections and sepsis. [ABSTRACT FROM AUTHOR]

Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown neuroprotective effects in obese mice. However, whether SGLT2i can ameliorate high-fat diet (HFD)-related ovulation disorders remains unknown. The aim of this research was to investigate whether dapagliflozin improves HFD-induced ovulatory dysfunction by attenuating microglia-mediated hypothalamic inflammation. Methods: C57BL/6J female mice fed HFD were treated with dapagliflozin (1 mg/kg) for 22 weeks. Plasma insulin, leptin, luteinizing hormone (LH), estradiol (E2), and IL-1β levels were also tested. Microglial morphology, cell numbers, and SGLT2 expression were evaluated using immunofluorescence. The expression of IL-1β, NLRP3, kisspeptin, gonadotropin-releasing hormone (GnRH), SGLT2, insulin, and leptin receptors in the hypothalamus was determined using immunohistochemical staining. We also examined the effects of dapagliflozin on glucose metabolism and the release of inflammatory factor in palmitic acid (PA)-treated HMC3 cells. Results: As expected, dapagliflozin improved HFD-induced metabolic disturbances, peripheral versus central insulin and leptin resistance and also restored the regular estrous cycle. Furthermore, dapagliflozin blunted microglia activation, NLRP3 inflammasome priming, hypothalamic inflammation, and increased the expression of GnRH and kisspeptin at proestrus in the hypothalamus. Additionally, dapagliflozin markedly reduced IL-6 and NO release and fat accumulation, decreased lactic acid production and glucose consumption, and inhibited mammalian target of rapamycin (mTOR) and hexokinase 2 (HK2) expression in PA-treated HMC3 cells. These effects suggest that dapagliflozin reduced the mTOR/HK2-mediated aerobic glycolysis. Conclusions: Dapagliflozin improved HFD-related ovulation disorders by regulating glucose metabolism through mTOR/HK2 signaling and attenuating microglia-mediated hypothalamic inflammation. These results validate the novel role for the neuroprotection of SGLT2i in HFD-induced obesity and ovulation disorders. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lead (Pb) is an ancient toxic metal and is still a major public health issue. Our previous study found that Pb exposure promotes metabolic disorders in obese mice, but the molecular mechanisms remain unclear. The present study explored the effects of Pb exposure on glucose homeostasis in mice fed a normal diet (ND) and high-fat diet (HFD) from the perspective of gut microbiota. RESULTS: Pb exposure had little effect on glucose metabolism in ND mice, but exacerbated hyperglycemia and insulin resistance, and impaired glucose tolerance in HFD mice. Pb exposure impaired intestinal tight junctions and mucin expression in HFD mice, increasing intestinal permeability and inflammation. Moreover, Pb exposure altered the composition and structure of the gut microbiota and decreased short-chain fatty acids (SCFAs) levels in HFD mice. Correlation analysis revealed that the gut microbiota and SCFAs were significantly correlated with the gut barrier and glucose homeostasis. Furthermore, the fecal microbiota transplantation from Pb-exposed HFD mice resulted in glucose homeostasis imbalance, intestinal mucosal structural damage and inflammation in recipient mice. However, Pb did not exacerbate the metabolic toxicity in HFD mice under depleted gut microbiota. CONCLUSION: The findings of the present study suggest that Pb induces impairment of glucose metabolism in HFD mice by perturbing the gut microbiota. Our study offers new perspectives on the mechanisms of metabolic toxicity of heavy metals and demonstrates that the gut microbiota may be a target of action for heavy metal exposure. [ABSTRACT FROM AUTHOR]

Aronia melanocarpa fruit contains a variety of active ingredients, such as phenolic acids, anthocyanins, proanthocyanidins, etc. Relevant in vivo and in vitro studies have concluded that it has beneficial effects in terms of treating dyslipidemia, hypertension, glucose metabolism disorders, etc. This article discusses the nutritional value and food processing of Aronia melanocarpa and reviews the chemical components of Aronia melanocarpa and the pharmacological activities of related substances in order to summarize the chemical characteristics of the fruit and its development prospects. The process optimization of juice production, the impact of antioxidant capacity, and the comprehensive utilization of pomace in feed are discussed. This article provides a reference for future comprehensive application research and product development of Aronia melanocarpa. [ABSTRACT FROM AUTHOR]

Maintaining blood glucose at an appropriate physiological level requires precise coordination of multiple organs and tissues. The vagus nerve bidirectionally connects the central nervous system with peripheral organs crucial to glucose mobilization, nutrient storage, and food absorption, thereby presenting a key pathway for the central control of blood glucose levels. However, the precise mechanisms by which vagal populations that target discrete tissues participate in glucoregulation are much less clear. Here we review recent advances unraveling the cellular identity, neuroanatomical organization, and functional contributions of both vagal efferents and vagal afferents in the control of systemic glucose metabolism. We focus on their involvement in relaying glucoregulatory cues from the brain to peripheral tissues, particularly the pancreatic islet, and by sensing and transmitting incoming signals from ingested food to the brain. These recent findings - largely driven by advances in viral approaches, RNA sequencing, and cell-type selective manipulations and tracings - have begun to clarify the precise vagal neuron populations involved in the central coordination of glucose levels, and raise interesting new possibilities for the treatment of glucose metabolism disorders such as diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Treatment strategies for depression based on interventions for glucose and lipid metabolism disorders are receiving increasing attention. Investigating the mechanism of their antidepressant effect and exploring new diagnostic and therapeutic biomarkers have attracted increasing attention. Dulaglutide, a long‐acting GLP‐1 receptor agonist, has been reported to alleviate cognitive deficits and neuronal damage. However, the antidepressant effect of dulaglutide and, especially, the underlying mechanism are still poorly understood. In this study, we aimed to explore the underlying biomarkers of depression and potential modulatory targets of dulaglutide in chronic mild stress (CMS) mice. Methods: Sixty mice were randomly divided into a control group (CON group), a CMS+Vehicle group (CMS+Veh group), a CMS+0.3 mg/kg dulaglutide group (Low Dula group), and a CMS+0.6 mg/kg dulaglutide group (High Dula group). Numerous behavioral tests, mainly the open field test, forced swimming test, and tail suspension test, were applied to evaluate the potential effect of dulaglutide treatment on anxiety‐ and depression‐like behaviors in mice exposed to chronic stress. Furthermore, a liquid chromatography–tandem mass spectrometry‐based metabolomics approach was utilized to investigate the associated mechanisms of dulaglutide treatment. Results: Three weeks of dulaglutide treatment significantly reversed depressive‐like but not anxiety‐like behaviors in mice exposed to chronic stress for 4 weeks. The results from the metabolomics analysis showed that a total of 20 differentially expressed metabolites were identified between the CON and CMS+Veh groups, and 46 metabolites were selected between the CMS+Veh and High Dula groups in the hippocampus of the mice. Comprehensive analysis indicated that lipid metabolism, amino acid metabolism, energy metabolism, and tryptophan metabolism were disrupted in model mice that experienced depression and underwent dulaglutide therapy. Conclusion: The antidepressant effects of dulaglutide in a CMS depression model were confirmed. We identified 64 different metabolites and four major pathways associated with metabolic pathophysiological processes. These primary data provide a new perspective for understanding the antidepressant‐like effects of dulaglutide and may facilitate the use of dulaglutide as a potential therapeutic strategy for depression. [ABSTRACT FROM AUTHOR]

Objective: Children born small for gestational age (SGA) are at a greater risk of developing insulin resistance, type 2 diabetes, and cardiovascular disease in adulthood. Gastrointestinal peptides, some secreted by intestinal L cells, regulate glucose and lipid metabolism and act on the hypothalamus to regulate energy homeostasis. The aim of this study was to explore whether gastrointestinal peptides are involved in metabolic disorders in SGA, which remains unclear. Methods: The secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were investigated in prepubertal children born SGA, the differences between catch-up growth and persistent short stature were compared, and correlation with glucose and lipid metabolism was analyzed. GLP-1, PYY, insulin-like growth factor 1, glucose, insulin, and lipid concentrations were analyzed in prepubertal children aged 4-10 years, stratified into three groups: short-SGA (SGA-s), catch-up growth SGA, and normal growth appropriate for gestational age (AGA). Results: Fasting GLP-1 and PYY concentrations were significantly lower in the SGA group than in the AGA group (p<0.05), and the GLP-1 level in infants born SGA with catch-up growth was lower than that in the SGA-s group (p<0.05). In the SGA population, GLP-1 showed a weak negative correlation with catch-up growth (r=-0.326) and positive correlation with fasting insulin (r=0.331). Conclusion: Lower GLP-1 concentrations may be associated with abnormal glucose metabolism in prepubertal children born SGA with catch-up growth. This is indirect evidence that impaired intestinal L cell function may be involved in the development of metabolic complications in SGA children. [ABSTRACT FROM AUTHOR]

Background: Alisol A can ameliorate glucose metabolism disorders, however, there is no data regarding its role in diabetic nephropathy (DN). The present work evaluates the role of Alisol A in DN and the underlying mechanism. Methods: RNA expression of circ_0001831, miR‐346, and lin‐28 homolog B (LIN28B) was detected by qRT‐PCR. Cell viability and proliferation were investigated by MTT assay and EdU assay, respectively. The inflammatory cytokines were examined by ELISAs. Oxidative stress was evaluated by the commercial kits. Protein expression was detected by western blotting. The interactions among circ_0001831, miR‐346, and LIN28B were identified by dual‐luciferase reporter assay and RIP assay. DN mouse model assay was used to analyse the effect of Alisol A on renal injury of diabetic mice. Results: HG treatment promoted HRMC proliferation, fibrosis, inflammation, and oxidative stress; however, these effects were reversed after Alisol A treatment. Alisol A treatment ameliorated STZ‐induced renal injury of diabetic mice. Additionally, circ_0001831 or LIN28B overexpression or miR‐346 downregulation relieved Alisol A‐induced effects under HG conditions. Mechanistically, circ_0001831 acted as a miR‐346 sponge, and LIN28B was identified as a target gene of miR‐346. Further, the regulation of circ_0001831 in HG‐induced HRMC dysfunction involved LIN28B. Conclusion: Alisol A ameliorated HG‐induced HRMC fibrosis, inflammation, and oxidative stress and STZ‐induced renal injury of diabetic mice by regulating the circ_0001831/miR‐346/LIN28B pathway. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a metabolic inflammatory disease with a high incidence worldwide. Patients with DM are at a high risk for all types of infections. Type 1 DM is characterised with immune destruction of pancreatic β cells, while type 2 diabetes is characterised with insulin resistance and β cell dysfunction, both of which result in disorders of glucose and lipid metabolism. This metabolic disorder causes functional defects of immune cells, aberrant production of inflammatory cytokines, dysregulated immune responses, advanced pathophysiological injury of the body, and increased mortality in populations with DM upon infections. Starting with the change of natural immune system in patients with DM, this paper focused on the enhanced severity of infections in DM and the underlying innate immune alterations in preclinical and clinical studies, aiming to better understand the influence of DM on the susceptibility, pathophysiology, and clinical outcomes in infections. [ABSTRACT FROM AUTHOR]

Endothelial damage caused by persistent glucose and lipid metabolism disorders is the main reason of diabetic vascular diseases. Daidzein exerts positive effects on vascular dysfunction. Peroxisome proliferator-activated receptors (PPARs) regulate critically glucose and lipid metabolism. However, the interaction of daidzein to PPARs is still insufficiently explored. In this study, the cell proliferation was detected by EdU. The intrinsic activity and binding affinity of daidzein for human PPARs (hPPARs) were estimated by transactivation reporter gene test and HPLC-UV method, respectively. Daidzein significantly reversed high glucose (HG, at 30 mmol/l)-induced injury in HUVECs, which was inhibited by both PPARα and PPARγ antagonist, but no PPARβ antagonist. Daidzein selectively activated hPPARα and hPPARγ1, but weakly hPPARβ. Additionally, daidzein also bound to both hPPARα and hPPARγ1. The findings suggested that daidzein may be a PPARα and PPARγ dual-agonist. The amelioration of daidzein on HUVECs from hyperglycemia may be mediated by the activation of PPARα and PPARγ receptors. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to compare the difference in abdominal fat distribution between different metabolic groups and find the ectopic fat with the most risk significance. Methods: A total of 98 subjects were enrolled; there were 53 cases in the normal glucose metabolism group and 45 cases in the abnormal glucose metabolism group. Chemical shift-encoded magnetic resonance imaging was applied for quantification of pancreatic fat fraction (PFF) and hepatic fat fraction (HFF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT). The correlation and the difference of fat distribution between different metabolism groups were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the suggestive effect of different body fat fraction. Results: Correlation analysis showed that body mass index (BMI) had the strongest correlation with fasting insulin (r = 0.473, p < 0.001), HOMA-IR (r = 0.363, p < 0.001), and C-reactive protein (r = 0.245, p < 0.05). Pancreatic fat has a good correlation with fasting blood glucose (r = 0.247, p < 0.05) and HbA1c (r = 0.363, p < 0.001). With the increase of BMI, PFF, VAT, and SAT showed a clear upward trend, but liver fat was distributed relatively more randomly. The pancreatic fat content in the abnormal glucose metabolism group is significantly higher than that in the normal group, and pancreatic fat is also a reliable indicator of abnormal glucose metabolism, especially in the normal and overweight groups (the area under the curve was 0.859 and 0.864, respectively). Conclusion: MR-based fat quantification techniques can provide additional information on fat distribution. There are differences in fat distribution among people with different metabolic status. People with more severe pancreatic fat deposition have a higher risk of glucose metabolism disorders. [ABSTRACT FROM AUTHOR]

The hepatokine leukocyte cell-derived chemotaxin-2 (LECT2) promotes insulin resistance and hepatic fibrogenesis. In rodents, acute exercise suppresses circulating LECT2; however, human data are lacking. This study compared circulating LECT2 across populations and explored whether acute exercise impacts circulating LECT2. In Part A (n = 43), data were pooled from three experimental studies, regarding the following groups: healthy individuals, individuals with impaired glycaemic regulation (IGR), and individuals with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (T2DM-MASLD). Generalised linear models assessed differences in circulating LECT2 among groups. Part B (n = 20) involved exercise (30 min, 65% peak oxygen uptake) and control (resting) trials in the healthy and IGR groups. Circulating LECT2 was measured before and at 0, 1, 2 and 3 h post-exercise. Generalised estimating equations assessed differences in LECT2 responses to the trials among groups. In Part A, circulating LECT2 levels were 28.7% and 37.3% higher in the IGR and T2DM-MASLD groups, vs. healthy individuals (p ≤ 0.038), with BMI identified as the main predictor (p = 0.008). In Part B, average circulating LECT2 levels were 6.3% higher after exercise vs. in the control (p < 0.001), with similar responses between groups (p = 0.829). In the combined cohort, circulating LECT2 levels were elevated 1–3 h after exercise vs. control (p ≤ 0.009). LECT2 is elevated in people with dysglycaemia, with BMI as a leading predictor. Contrary to previous rodent work, acute exercise augments, rather than suppresses, circulating LECT2 in humans. [ABSTRACT FROM AUTHOR]

Background Porphyromonas gingivalis (Pg.) is the main pathogen of periodontitis. Studies have found that Pg. can affect systemic diseases including type 2 diabetes mellitus (T2DM) through oral-intestinal pathway, but its specific mechanism remains unclear. Objective To explore whether Pg. has an effect on T2DM by changing intestinal mechanical and immune barriers. Methods A total of 24 among 40 SPF mice were randomly selected to construct T2DM models, among the successful models, 16 mice were selected to be divided into the model group (DM group, n=8) and model+Pg. group (PD group, n=8), and the other 16 mice were divided into the control group (N group, n=8) and Pg. group (n=8). After modeling, body mass and fasting plasma glucose (FPG) of mice were observed, and oral glucose tolerance test (OGTT) was performed at the 5th week, OGTT curve was plotted and the area under the curve (AUC) was calculated. Pg. group and PD group were gavaged with Pg. bacterial solution from the 7th week for 5 consecutive weeks. Lipopolysaccharide (LPS) was determined by enzyme-related immunosorbent assay (ELISA), colonic tight-junction protein and inflammatory factors were detected by real-time fluorescence quantitative PCR, and colonic tissue lesions were observed by hematoxylin-eosin (HE) staining. Pearson correlation or Spearman correlation analysis was used to investigate the relationship of FPG with colonic tight junction protein mRNA expression and serum LPS levels in mice. Results Body weight of DM group was higher than that of N group and Pg. group at 2nd to 6th weeks before irrigation (P

BACKGROUND. Glucose metabolism disorders (GMD) were detected both in acute and in post-COVID, however, its pathogenic aspects remain unclear.AIM. To analyze the occurrence of GMD in post-COVID patients who have had moderate and severe COVID-19 without previously known GMD disorders, and evaluate expression of SARS-CoV-2 proteins and its entry factors in pancreas in acute COVID-19.METHODS. Among 187 hospitalized patients with confirmed COVID-19 141 patients without previously diagnosed GMD underwent follow-up post-COVID visits. The examination for all patients included anthropometric measurement with calculation of BMI, level of HbA1c and fasting plasma glucose, for 106 patients level of insulin and HOMA-IR index was analyzed. For histological examination, pancreas fragments of 20 patients with fatal outcome were selected. Immunohistochemical study was performed with antibodies to SARS-CoV-2, ACE2, DPP4, as well as double-labeled immunofluorescence microscopy (insulin-SARS-CoV-2, insulin-ACE2, insulin-DPP4).RESULTS. Among 141 patients in post-COVID period, 9 (6.3%) had HbA1c or fasting plasma glucose levels that met criteria for diabetes mellitus, 38 (26.9%) — exceeded normal values (WHO), and 84 (59.6%) had GMD according to criteria of the ADA. In post-COVID, patients with GMD had a higher BMI and HOMA-IR index (p=0.001) compared to patients with normal glycemic levels. Only 40.4% of people had HOMA-IR index above 2.7. Patients with GMD had higher level of CRP (p=0.007) and a maximum glucose level (p=0.019) in the acute period. Positive relationship was found between BMI and HOMA index both in acute (p

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The pathogenesis of diabetes is accompanied by increased levels of inflammatory factors, also known as "metabolic inflammation", which runs through the whole process of the occurrence and development of the disease. Mitochondria, as the key site of glucose and lipid metabolism, is often accompanied by mitochondrial function damage in type 2 diabetes mellitus (T2DM). Damaged mitochondria release pro‐inflammatory factors through damage‐related molecular patterns that activate inflammation pathways and reactions to oxidative stress, further aggravate metabolic disorders, and form a vicious circle. Currently, the pathogenesis of diabetes is still unclear, and clinical treatment focuses primarily on symptomatic intervention of the internal environment of disorders of glucose and lipid metabolism with limited clinical efficacy. The proinflammatory effect of mitochondrial damage‐associated molecular pattern (mtDAMP) in T2DM provides a new research direction for exploring the pathogenesis and intervention targets of T2DM. Therefore, this review covers the most recent findings on the molecular mechanism and related signalling cascades of inflammation caused by mtDAMP in T2DM and discusses its pathogenic role of it in the pathological process of T2DM to search potential intervention targets. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors (GPCRs) are a large family of membrane protein receptors, and Takeda G protein-coupled receptor 5 (TGR5) is a member of this family. As a membrane receptor, TGR5 is widely distributed in different parts of the human body and plays a vital role in regulating metabolism, including the processes of energy consumption, weight loss and blood glucose homeostasis. Recent studies have shown that TGR5 plays an important role in glucose and lipid metabolism disorders such as fatty liver, obesity and diabetes. With the global obesity situation becoming more and more serious, a comprehensive explanation of the mechanism of TGR5 and filling the gaps in knowledge concerning clinical ligand drugs are urgently needed. In this review, we mainly explain the anti-obesity mechanism of TGR5 to promote the further study of this target, and show the electron microscope structure of TGR5 and review recent studies on TGR5 ligands to illustrate the specific binding between TGR5 receptor binding sites and ligands, which can effectively provide new ideas for ligand research and promote drug research. TGR5 can serve as an effective target for the treatment of obesity by regulating thermogenesis, metabolism, inflammation and appetite. [Display omitted] [ABSTRACT FROM AUTHOR]

Simple Summary: Glucose metabolism was the first metabolic pathway to be discovered and serves a central role across all life by generating energy. Cancer cells hijack glycolysis to promote growth and metastasis. Understanding the molecular basis of glycolytic rewiring in cancers could illuminate new treatment approaches. Glycolysis is the central metabolic pathway across all kingdoms of life. Intensive research efforts have been devoted to understanding the tightly orchestrated processes of converting glucose into energy in health and disease. Our review highlights the advances in knowledge of how metabolic and gene networks are integrated through the precise spatiotemporal compartmentalization of rate-limiting enzymes. We provide an overview of technically innovative approaches that have been applied to study phosphofructokinase-1 (PFK1), which represents the fate-determining step of oxidative glucose metabolism. Specifically, we discuss fast-acting chemical biology and optogenetic tools that have delineated new links between metabolite fluxes and transcriptional reprogramming, which operate together to enact tissue-specific processes. Finally, we discuss how recent paradigm-shifting insights into the fundamental basis of glycolytic regulatory control have shed light on the mechanisms of tumorigenesis and could provide insight into new therapeutic vulnerabilities in cancer. [ABSTRACT FROM AUTHOR]

Introduction: Visfatin and nesfatin are active proteins that are involved in the regulation of physiological functions such as glucose metabolism and inflammatory response. This study aimed to assess the influence of visfatins and nystatins gene variants on the occurrence of the full metabolic syndrome or its components. Material and methods: The research cohort comprised 285 diabetic patients, 132 men and 153 women. Specific DNA segments were amplified and labelled, and the rs 4730153 gene of visfatin and the rs 1330 gene of nesfatin were analysed. Real-Time PCR was conducted using fluorescence-labelled probes. Results: The AA genotype of visfatin (rs 4730153) shows a positive association with glucose concentration or pharmacological treatment in patients with type 2 diabetes, compared to AG and GG genotypes. The GG genotype of nesfatin (rs 1330) shows a positive association with incidents of metabolic syndrome, compared to the AA genotype. Conclusions: Visfatin polymorphism in rs 4730153 may be associated with inappropriate glucose concentration. Nesfatin polymorphism in rs 1330 may be associated with metabolic syndrome. Further studies in a larger group of patients are necessary to completely assess this association. [ABSTRACT FROM AUTHOR]

To analyze the relationship between intestinal flora and glucose metabolism changes in CGIUGR rats by interventing CG-IUGR rats with the intestinal flora of normal rats. Methods SD rats were divided into three groups: the control group, the CG-IUGR group and the CG-IUGR+intestinal bacteria group (n=8 in each group). The CG IUGR rat model was established by low-calorie diet. The intestinal flora of rats in the control group were transplanted into CG-IUGR rats in the CG-IUGR+intestinal bacteria group at 3-week-old (once a week, 6 times in total). From birth to 8 weeks, the body weight and body length were measured in three groups of rats, and body mass index (BMI) was calculated. The relevant indexes of glucose metabolism were detected in three groups, including fasting blood glucose (FBG), serum fasting insulin (FINS) and serum insulin (INS) at 15 min after glucose loading and tolerance test of glucose and insulin. The mRNA and protein expression levels of skeletal muscle glycogen synthase (GYS)1 and liver GYS2 were detected by realtime fluorescence quantitative polymerase chain reaction (qPCR) and Western blot assay respectively. The activities of GYS in skeletal muscle and liver were detected. 16S rDNA sequencing was used to detect the diversity and composition of intestinal flora in rats of three groups. Results Compared with the control group, the body length, body weight and BMI of rats in the CG-IUGR group were all increased significantly during the process of growth and development. Its serum FINS level decreased, and serum FBG had no significant change. The blood glucose levels of rats in the CG-IUGR group were significantly up-regulated after glucose and INS loading. The serum INS level of rats in the CG-IUGR group was significantly up-regulated at 15 min after glucose loading. The mRNA and protein expression levels of skeletal muscle GYS1 and liver GYS2 in rats of the CG-IUGR group were decreased, and the activity of GYS was also decreased (P＜0.05). These above changes of rats in the CG-IUGR+intestinal bacteria group were all improved (P＜0.05). Compared with the control group, ACE and Chao1 indices of intestinal bacteria in rats of the CG-IUGR group were lower (P＜0.05). Compared with the CG-IUGR group, the relative abundance of intestinal bifidobacterium in rats of the CG-IUGR+intestinal bacteria group was increased (P＜0.05). Conclusion IUGR can attenuate the glucose metabolism fuction of CG-IUGR rats by downregulating the expression and activity of GYS in skeletal muscle and liver tissue. The abnormal glucose metabolism in CGIUGR rats is related to changes of intestinal flora. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome (PCOS) is characterized by obesity, glucose intolerance, dyslipidemia, and hyperandrogenemia. Although several, placebo-controlled 2x2 factorial design, randomized controlled trials have tested the efficacy of dietary and herbal supplements in controlling these parameters in PCOS patients, these studies are not suitable for a comparative efficacy assessment across these supplements. Herein, a protocol for systematic review and network meta-analysis (NMA) is presented to make such a comparison. PubMed, Embase, and Scopus, were interrogated to identify relevant trials, published in English, factors to be investigated will include dietary factors, micronutrients, choline, essential fatty acids, and herbal extracts. Other factors to be considered include trial design, population characteristics, interventions compared, and outcomes of interest. The revised Cochrane tool was used for the appraisal of eligible trials. NMA (frequentist method) will be used for respective outcomes to compare effect sizes (weighted or standardized mean difference) among the interventions. Both logical and statistical (inconsistency assessment) approaches will be used to minimize intransitivity risk. The surface under the cumulative ranking curve values will be used to gauge the best intervention for outcomes with a statistically significant effect size suggesting a favorable outcome. Additionally, the exploration of interrelation among interventions and the small study effect in respective NMA models will be investigated using network maps and comparison-adjusted funnel plots, respectively. Statistical significance is assumed at p<0.05 with 95% confidence interval. Stata statistical software (v16) was used for analysis. The study was registered with PROSPERO, registration number: CRD42022301530. [ABSTRACT FROM AUTHOR]

BACKGROUND: Foxtail millet (Setaria italica) is a whole millet grain that has been considered for improving the disorder of glucose and lipid metabolism. The purpose of the work is to explore the extraction and enrichment of polyphenols from foxtail millets which can regulate the disorder of glucose and lipid metabolism by increasing endogenous GLP‐1 (glucagon‐like peptide‐1). RESULTS: The optimum ultrasound‐assisted extraction (UAE) of foxtail millet polyphenols (FMPs) was as follows: 70 °C and 400 W and 70% ethanol concentration, further purification using macroporous resin. In vitro, the FMP eluent of 60% ethanol (FMP‐60) has the best effect in promoting GLP‐1 secretion from L cells among the different active components of FMP. Millet polyphenols (MPs) were obtained from finishing foxtail millet with the bran removed by the same extraction and purification method. Compared with MP‐60, FMP‐60 mainly included eight active phenolic constituents and contained more ferulic acid, p‐coumaric acid, 2‐hydroxycinnamic acid, and coniferaldehyde. After gavage treatment of diet‐induced obese (DIO) mice with FMP‐60, FMP‐60 promoted endogenous GLP‐1 secretion in mice and ameliorated disorders of glucolipid metabolism in DIO mice. CONCLUSION: FMP‐60 could improve glucose homeostasis and ameliorates metabolic disease by promoting the endogenous GLP‐1 level and preventing weight gain in DIO mice. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Yuquan Pill (YQW) is a modern concentrated pill preparation of six herbs, namely, Ge Gen (Pueraria lobata Ohwi), Di huang (Rehmannia glutinosa Libosch.), Tian Huafen (Trichosanthes kirilowii Maxim.), Mai Dong (Ophiopogon japonicus (L. f.) Ker Gawl.), Wu Weizi (Schisandra chinensis (Turcz.) Baill.) and Gan Cao (Glycyrrhiza uralensis Fisch.). It is extensively used to treat type 2 diabetesrelated glucose and lipid metabolism disorders. But what's the pharmacodynamic substance and how it works in the treatment of Type 2 diabetes mellitus (T2DM) are still unclear. Purpose: The purpose of this study is to determine the likely pharmacological components and molecular mechanism of YQW's intervention on T2DM by combining serum pharmacochemistry, network analysis and transcriptomics. Methods: The efficacy and prototypical components of blood entry were determined after oral administration of YQW aqueous solution to T2DM rats induced by high-fat feed and low-dose streptozotocin (STZ), and the key targets and pathways for these compounds to intervene in T2DM rats were predicted and integrated using network analysis and transcriptomics techniques. Results: In diabetic rats, YQW can lower TG, CHO, NO, and MDA levels (p < 0.05) while increasing HDL-C levels (p < 0.01), and protecting the liver and kidney. 22 prototype components (including puerarin, daidzein, 3'-methoxypuerarin, and liquiritigenin, among others) were found in the serum of rats after oral administration of YQW for 90 min, which might be used as a possible important ingredient for YQW to intervene in T2DM rats. 538 YQW pharmacodynamic components-related targets and 1,667 disease-related targets were projected through the PharmMapper database, with 217 common targets between the two, all of which were engaged in regulating PI3K-Akt, MAPK, Ras and FoxO signal pathway. Finally, the mRNA expression profiles of liver tissues from rats in the control, model, and YQW groups were investigated using highthroughput mRNA sequencing technology. YQW can regulate the abnormal expression of 89 differential genes in a disease state, including 28 genes with abnormally high expression and 61 genes with abnormally low expression. Five common genes (Kit, Ppard, Ppara, Fabp4, and Tymp) and two extensively used regulatory pathways (PI3K-Akt and MAPK signaling pathways) were revealed by the integrated transcriptomics and network analysis study. Conclusion: The mechanism of YQW's intervention in T2DM rats could be linked to 22 important components like puerarin, daidzein, and glycyrrhetinic acid further activating PI3K-Akt and MAPK signaling pathways by regulating key targets Kit, Ppard, Ppara, Fabp4, and Tymp, and thus improving lipid metabolism disorder, oxidative stress, and inflammation levels in T2DM rats. On the topic, more research into the pharmacological ingredient foundation and mechanism of YQW intervention in T2DM rats can be done. [ABSTRACT FROM AUTHOR]

Purpose: E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism. Methods: This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47. Results: E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre-vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30 min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission. Conclusion: E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such as dyslipidemia. [ABSTRACT FROM AUTHOR]

Obesity is currently one of the most significant public health challenges worldwide due to the continuous increase in obesity rates among children, especially younger children. Complications related to obesity, including serious ones, are increasingly being diagnosed in younger children. A search was performed from January 2023 to September 2023 using the PubMed, Cochrane Library, Science Direct, MEDLINE, and EBSCO databases. The focus was on English-language meta-analyses, systematic reviews, randomized clinical trials, and observational studies worldwide. Four main topics were defined as follows: disorders of glucose metabolism; liver disease associated with childhood obesity; the relationship between respiratory disorders and obesity in children; and the effects of obesity on the hypothalamic–pituitary–gonadal axis and puberty. Understanding potential complications and their underlying mechanisms can expedite the diagnostic process and enhance the effectiveness of treatment. We aspire that this study will bring insight into the often-overlooked complications associated with obesity. [ABSTRACT FROM AUTHOR]

This document is an editorial published in Frontiers in Endocrinology titled "The relationship between diabetes and cancers and its underlying mechanisms, volume II." The editorial discusses the potential relationship between diabetes mellitus (DM) and cancer morbidity or mortality. It highlights studies that have found a higher risk of developing oral cancer and potentially malignant disorders in patients with DM, as well as the association between DM and hepatocellular carcinoma. The editorial emphasizes the need for clinical trials in humans to further understand the roles of diabetes in cancer development and the importance of cancer screening in patients with DM. [Extracted from the article]

Diabetes mellitus (DM) is now regard as a worldwide health issue affecting hundreds millions of people. It is a metabolic disease targeting glucose metabolism and insulin homeostasis, Type 2 diabetes mellitus (T2DM) is the most prevent type of this disease accounting about 90-95% of the disease as whole. microRNAs (miRNAs) which are a small non-coding RNAs, they revolutionized as potential new biomarkers for the diagnosis and prognosis of a wide range of disorders. Recent studies prove the relationship between miR-21 and inflammatory process and insulin resistance, our emphasis suggest there is a role of miR-21 in insulin resistance in T2DM. Studies have explored the potential of miR-21 as diagnostic biomarkers for T2DM. The purpose of this study is to compare the sera levels of miRNA-21 among newly diagnosed patients e with T2DM patients with their levels in apparently healthy subjects using blood samples. The time frame for this case-control research is August 2022 through March 2023, and it took place at Al-Sadr Teaching Hospital/Masin / Iraq. There were 100 patients home recent diagnosed with T2DM (50 females and 50 males) with age ranged between (20 -70 years) and 100 apparently healthy subject who dealt with as control group. 2 ml of blood drown from each patient and healthy person, putted it in EDTA tube with 1 ml of Trizole as a preservative, and put the tubes in the freezer at -70 degrees Celsius until analyze the samples. [ABSTRACT FROM AUTHOR]

Introduction: Menopause is a condition for metabolic disorders. This study aimed to evaluate the effect of Nigella sativa (NS), curcumin nanomicelle (CN), lipid profile, glycemic status and 17-β estradiol (ES) levels in postmenopausal women. Methods: Triple-blind randomized clinical trial was conducted on 120 postmenopausal women. Participants were randomly assigned to four groups: 1) NS capsule 1000 mg and CN placebo, 2) 80 mg CN capsule and NS placebo, 3) both NS and CN capsules and 4) NS and CN placebo. Participants received a single dose daily for 6 months. The serum lipid profile, glycemic control biomarkers, and ES were measured pre-and post-intervention using biochemical methods. Results: Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, fasting blood sugar (FBS), fasting insulin (FI), insulin resistance (IR), and ES showed significant improvement in NS group. CN significantly reduced TC, FI, and IR, and significantly increased ES. The combination of NS-CN significantly decreased TC, LDL, FI, and IR, and increased HDL and ES. The comparison of the studied with the placebo groups showed that these changes were significant in glycemic indices and NS significantly increased estrogen. Conclusion: NS, CN and NS-CN improved lipid profiles, blood sugar, and hormone levels. However, this improvement was significant in glycemic indices and estrogen levels compared to the placebo group. No superiority of combined NS-CN over NS or CN was found in this trial.

AIMS: To evaluate the performance of the WATCH-DM risk score, a clinical risk score for heart failure (HF), in patients with dysglycaemia and in combination with natriuretic peptides (NPs). METHODS AND RESULTS: Adults with diabetes/pre-diabetes free of HF at baseline from four cohort studies (ARIC, CHS, FHS, and MESA) were included. The machine learning- [WATCH-DM(ml)] and integer-based [WATCH-DM(i)] scores were used to estimate the 5-year risk of incident HF. Discrimination was assessed by Harrells concordance index (C-index) and calibration by the Greenwood-Nam-DAgostino (GND) statistic. Improvement in model performance with the addition of NP levels was assessed by C-index and continuous net reclassification improvement (NRI). Of the 8938 participants included, 3554 (39.8%) had diabetes and 432 (4.8%) developed HF within 5 years. The WATCH-DM(ml) and WATCH-DM(i) scores demonstrated high discrimination for predicting HF risk among individuals with dysglycaemia (C-indices = 0.80 and 0.71, respectively), with no evidence of miscalibration (GND P ≥0.10). The C-index of elevated NP levels alone for predicting incident HF among individuals with dysglycaemia was significantly higher among participants with low/intermediate (

Purpose: The aim of our study is to estimate the associations and causalities of glucose metabolism traits of fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), and 2-h glucose post-challenge (2hGlu) with sleep traits consisting of excessive daytime sleepiness (EDS), insomnia, and sleep duration. Methods: We employed standard quantitative analysis procedures to assess the associations between sleep traits and glucose metabolism. Moreover, we acquired published genome-wide association studies (GWAS) summary statistics for these traits and conducted Mendelian randomization (MR) analyses to estimate their causal directions and effects. Inverse variance weighting (IVW) was employed as the primary approach, followed by sensitivity analyses. Results: A total of 116 studies with over 840,000 participants were included in the quantitative analysis. Our results revealed that participants with abnormal glucose metabolism had higher risks for EDS (OR [95% CI] = 1.37 [1.10,1.69]), insomnia (OR [95% CI] = 1.65 [1.24,2.20]), and both short and long sleep duration (OR [95% CI] = 1.35 [1.12,1.63]; OR [95% CI] = 1.38 [1.13,1.67] respectively). In addition, individuals with these sleep traits exhibited alterations in several glycemic traits compared with non-affected controls. In MR analysis, the primary analysis demonstrated causal effects of 2hGlu on risks of EDS (OR [95% CI] = 1.022 [1.002,1.042]) and insomnia (OR [95% CI] = 1.020[1.001,1.039]). Furthermore, FINS was associated with short sleep duration (OR [95% CI] = 1.043 [1.018,1.068]), which reversely presented a causal influence on HbA1c (b [95% CI] = 0.131 [0.022,0.239]). These results were confirmed by sensitivity analysis. Conclusion: Our results suggested mutual risk and causal associations between the sleep traits and glycemic traits, shedding new light on clinical strategies for preventing sleep disorders and regulating glucose metabolism. Future studies targeting these associations may hold a promising prospect for public health. [ABSTRACT FROM AUTHOR]

BACKGROUND: The intestinal flora is primarily responsible for maintaining the balance between host defense and immune tolerance. In addition, the intestinal flora is closely related to autoimmune diseases, and exercise has an important regulatory effect on the intestinal flora, which in turn affects the occurrence and development of various autoimmune diseases. OBJECTIVE: To summarize the effect of intestinal flora on different autoimmune diseases such as type 1 diabetes, celiac disease, inflammatory bowel disease, multiple sclerosis and ankylosing spondylitis, and to analyze the effect of exercise on the intestinal flora and the effect of exercise in regulating the intestinal flora on autoimmune protection, aiming to provide a new reference and basis for the prevention and treatment of autoimmune diseases. METHODS: PubMed and CNKI databases were searched for relevant articles published between 1996 and 2022 using the keywords of “Intestinal flora, intestinal bacteria, autoimmune diseases, type 1 diabetes, celiac disease, inflammatory bowel disease, multiple sclerosis, ankylosing spondylitis, exercise” in English and Chinese, respectively. Finally 90 studies were selected according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION: Autoimmune diseases such as type 1 diabetes, celiac disease, inflammatory bowel disease, multiple sclerosis and ankylosing spondylitis are affected by the intestinal flora, and the intestinal flora plays a key role in the regulation of autoimmune diseases. Different exercise modes have different effects on the intestinal flora. Aerobic exercise can increase the diversity and abundance of intestinal flora in the body, improve the immune barrier function of the intestinal mucosa, reduce the metabolic inflammatory response of the body, thereby promoting health and enhancing the body’s resistance. However, the pathways and specific mechanisms of aerobic exercise regulating the intestinal flora and promoting body health need further studies. The effect of anaerobic exercise on the intestinal flora of the body is still controversial, which may be related to the heterogeneity of the study object, research method, and time intensity of exercise intervention and needs further digging. However, studies have shown that anaerobic exercise can improve the health of the body by reducing the body’s inflammatory response, improving insulin resistance and improving glucose and lipid metabolism disorders. Exercise can play an important role in the prevention and treatment of autoimmune diseases by regulating the intestinal flora, inhibiting inflammatory response, regulating intestinal flora homeostasis and improving blood glucose homeostasis, thereby providing new ideas and strategies for exercise to promote physical health and the prevention and treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) remains a major cause of liver-related morbidity and mortality worldwide. Tea polyphenols (TPs) possess strong antioxidant activity; cassia seed extract (CSE) has the effect of brightening the eyes; and Ampelopsis grossedentata extract (AGE) has the function of protecting the liver. However, the synergistic hepatoprotective effect of TP, AGE and CSE as a joint formulation is unknown. This study aimed to investigate the role of a tea solid beverage, composed of TP, AGE and CSE, on chronic alcoholic liver injury in rats and its underlying mechanisms via the analysis of transcriptomics and gut microbiota. The histopathological findings revealed that the tea solid beverage could reduce the production of fat vacuoles and inflammatory cell infiltration. Additionally, the tea solid beverage was found to effectively relieve the increase in the AST (from 424.85 U/L to 180.17 U/L), ALT (from 139.95 U/L to 85.88 U/L) and LDH (from 21.16 U/L to 13.35 U/L) enzyme activities and the expression of the inflammatory factors TNF-α (from 394.02 pg/mL to 214.44 pg/mL) and IL-6 (from 208.46 pg/mL to 116.59 pg/mL) caused by alcohol consumption. Further, it significantly enhanced the GSH concentration (from 4.53 pg/mL to 8.08 pg/mL) and SOD activity (from 84.70 U/mL to 156.94 U/mL) and decreased the MDA (from 58.61 mmol/mL to 36.58 mmol/mL) and TG (from 7.07 mmol/L to 3.43 mmol/L)) concentrations in the liver of rats. The analysis and identification of transcriptomics showed that the tea solid beverage intervention primarily protected the liver of rats with chronic alcoholic injury by up-regulating the differential gene Hmgcs1 in order to increase the synthesis of ketone bodies and by down-regulating the differential gene Pfkfb1 for the purpose of decreasing the glucose metabolism. Additionally, it was found that the tea solid beverage could significantly change the composition of intestinal flora in drinking rats by regulating mineral absorption, the pathways of bile secretion, the adipocytokine signaling pathway and the peroxisome balance of the intestinal flora, in order to protect alcohol-drinking rats' livers. In conclusion, the tea solid beverage, consisting of TP, AGE and CSE, is a functional drink that prevents ketone metabolism, glucose metabolism and microbiome disorders induced by alcohol intake. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension (PAH) is a chronic and progressive disease that is strongly associated with dysregulation of glucose metabolism. Alterations in nuclear receptor subfamily 4 group A member 1 (NR4A1) activity alter the outcome of PAH. This study aimed to investigate the effects of NR4A1 on glycolysis in PAH and its underlying mechanisms. Methods: This study included twenty healthy volunteers and twenty-three PAH patients, and plasma samples were collected from the participants. To mimic the conditions of PAH in vitro, a hypoxia-induced model of pulmonary artery smooth muscle cell (PASMC) model was established. The proliferation of PASMCs was assessed using CCK8 assays. Results: Levels of NR4A1, hypoxia-inducible factor-1α (HIF-1α), and various glycolysis-related enzymes were measured. In addition, extracellular glucose and lactate production were assessed. The interaction between NR4A1 and HIF-1α was evaluated by co-immunoprecipitation assays. Levels of NR4A1 and HIF-1α was increased in PAH patients, and exposure to hypoxia resulted in increased levels of NR4A1 and HIF-1α in PASMCs. NR4A1 interacted with HIF-1α. NR4A1 overexpression enhanced hypoxia-induced expression of HIF-1α, GLUT1, PKM2, HK2, and CD36, decreased glucose levels, increased lactate levels and promoted hypoxic PASMC viability. Conversely, silencing NR4A1 decreased hypoxia-induced expression of HIF-1α, GLUT1, PKM2, HK2, and CD36, promoted glucose production, reduced lactate levels and inhibited hypoxic PASMC viability. Furthermore, overexpression of HIF-1α reversed the regulation of glycolysis caused by NR4A1 knockdown. Conclusion: NR4A1 enhances glycolysis in hypoxia-induced PASMCs by upregulating HIF-1α. Our findings indicate that the management of NR4A1 activity may be a promising strategy for PAH therapy. [ABSTRACT FROM AUTHOR]

Introduction: Current use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on the risk of glucose metabolism disorders is still controversial. Material and methods: This was a prospective, longitudinal birth cohort study with long‐term follow‐up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2‐h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin‐only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253). Results: Compared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio [OR] 3.9, 95% confidence interval [CI]: 1.6–9.2) but not of type 2 diabetes mellitus. Former progestin‐only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol‐lowering medication. Conclusions: Former long‐term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the primary cause of dementia and is anticipated to impose a substantial economic burden in the future. Over a significant period, the widely accepted amyloid cascade hypothesis has guided research efforts, and the recent FDA approval of an anti-amyloid-beta (Aβ) protofibrils antibody, believed to decelerate AD progression, has further solidified its significance. However, the excessive emphasis placed on the amyloid cascade hypothesis has overshadowed the physiological nature of Aβ and tau proteins within axons. Axons, specialized neuronal structures, sustain damage during the early stages of AD, exerting a pivotal influence on disease progression. In this review, we present a comprehensive summary of the relationship between axonal damage and AD pathology, amalgamating the physiological roles of Aβ and tau proteins, along with the impact of AD risk genes such as APOE and TREM2. Furthermore, we underscore the exceptional significance of axonal damage in the context of AD. [ABSTRACT FROM AUTHOR]

Catabolite control protein A (CcpA), an important global regulatory protein, is extensively found in S. aureus. Many studies have reported that CcpA plays a pivotal role in regulating the tricarboxylic acid cycle and pathogenicity. Moreover, the CcpA-knockout Staphylococcus aureus (S. aureus) in diabetic mice, compared with the wild-type, showed a reduced colonization rate in the tissues and organs and decreased inflammatory factor expression. However, the effect of CcpA-knockout S. aureus on the host's energy metabolism in a high-glucose environment and its mechanism of action remain unclear. S. aureus, a common and major human pathogen, is increasingly found in patients with obesity and diabetes, as recent clinical data reveal. To address this issue, we generated CcpA-knockout S. aureus strains with different genetic backgrounds to conduct in-depth investigations. In vitro experiments with high-glucose-treated cells and an in vivo model study with type 1 diabetic mice were used to evaluate the unknown effect of CcpA-knockout strains on both the glucose and lipid metabolism phenotypes of the host. We found that the strains caused an abnormal metabolic phenotype in type 1 diabetic mice, particularly in reducing random and fasting blood glucose and increasing triglyceride and fatty acid contents in the serum. In a high-glucose environment, CcpA-knockout S. aureus may activate the hepatic STAT5/PDK4 pathway and affect pyruvate utilization. An abnormal metabolic phenotype was thus observed in diabetic mice. Our findings provide a better understanding of the molecular mechanism of glucose and lipid metabolism disorders in diabetic patients infected with S. aureus. [ABSTRACT FROM AUTHOR]

The liver is the primary organ regulating glucose metabolism. In our recent study, cinnamon improved liver function in diabetic mice. However, it is not clear whether cinnamon can reduce the glycemia of diabetic animals by regulating liver glucose metabolism. The purpose of this study was to investigate the hypoglycemic mechanism of cinnamon powder (CP) from the perspective of regulating liver glucose metabolism. To achieve this, different doses of CP (200, 400, or 800 mg/kg body weight) were given to diabetic mice by gavage once per day for 8 weeks. These mice were compared with healthy controls, untreated diabetic mice, and diabetic mice treated with metformin (the main first-line drug for type 2 diabetes). CP treatment effectively reduced fasting blood glucose levels and food intake, improved glucose tolerance and fasting serum insulin levels, and decreased glycated serum protein levels in diabetic mice. Furthermore, treatment with CP increased liver glycogen content and reduced the level of the gluconeogenesis precursor pyruvate in the liver. Data obtained by qPCR and western blotting suggested that CP improved glucose metabolism disorders by regulating AMPKα/PGC1α-mediated hepatic gluconeogenesis and PI3K/AKT-mediated hepatic glycogen synthesis. CP exhibits good hypoglycemic effects by improving hepatic glycogen synthesis and controlling hepatic gluconeogenesis. Therefore, CP may be applied as a functional food to decrease blood glucose. [ABSTRACT FROM AUTHOR]

Cushing's syndrome, acromegaly and neuroendocrine disorders are characterized by an excess of counterregulatory hormones, able to induce insulin resistance and glucose metabolism disorders at variable degrees and requiring immediate treatment, until patients are ready to undergo surgery. This review focuses on the management of diabetes mellitus in endocrine disorders related to an excess of counterregulatory hormones. Currently, the landscape of approved agents for treatment of diabetes is dynamic and is mainly patient-centred and not glycaemia-centred. In addition, personalized medicine is more and more required to provide a precise approach to the patient's disease. For this reason, we aimed to define a practical therapeutic algorithm for management of diabetes mellitus in patients with glucagonoma, pheochromocytoma, Cushing's syndrome and acromegaly, based on our practical experience and on the physiopathology of the specific endocrine disease taken into account. This document is addressed to all specialists who approach patients with diabetes mellitus secondary to endocrine disorders characterized by an excess of counterregulatory hormones, in order to take better care of these patients. Care and control of diabetes mellitus should be one of the primary goals in patients with an excess of counterregulatory hormones requiring immediate and aggressive treatment. [ABSTRACT FROM AUTHOR]

Identifying non‐diabetic hyperglycaemia (NDH) and intervening to halt the progression to type 2 diabetes has become an essential component of cardiovascular and cerebrovascular risk reduction. Diabetes prevention programs have been instigated to address the increasing prevalence of NDH and type 2 diabetes by targeting lifestyle modifications. Evidence suggests that the risk of progression from NDH to type 2 diabetes declines with age, and that a diagnosis of type 2 diabetes in older adults is not associated with the same risk of adverse consequences as it is in younger age groups. The current definition of NDH is not adjusted based on a person's age. Therefore, there is debate about the emphasis that should be placed upon a diagnosis of NDH in older adults. This article will explore the evidence and current clinical practice surrounding dysglycaemia through the spectrum of different age ranges, and the potential implications this has for older adults. [ABSTRACT FROM AUTHOR]

Purpose: Methyl triclosan (MTCS) is one of the biomethylated by-products of triclosan (TCS). With the increasing use of TCS, the adverse effects of MTCS have attracted extensive attention in recent years. The purpose of this study was to investigate the cytotoxicity of MTCS and to explore the underlining mechanism using human hepatocyte L02 cells as in vitro model. Results: The cytotoxicity results revealed that MTCS could inhibit cell viability, disturb the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG), and reduce the mitochondrial membrane potential (MMP) in a dose-dependent manner. In addition, MTCS exposure significantly promoted the cellular metabolic process, including enhanced conversion of glucose to lactic acid, and elevated content of intracellular triglyceride (TG) and total cholesterol (TC). RNA-sequencing and bioinformatics analysis indicated disorder of glucose and lipid metabolism was significantly induced after MTCS exposure. Protein-protein interaction network analysis and node identification suggested that Serine hydroxy methyltransferase 2 (SHMT2), Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), Asparagine synthetase (ASNS) and Phosphoglycerate dehydrogenase (PHGDH) are potential molecular markers of metabolism imbalance induced by MTCS. Conclusion: These results demonstrated that oxidative stress and metabolism dysregulation might be involved in the cytotoxicity of MTCS in L02 cells. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus is one of the most common endocrine diseases that occur during pregnancy. Disorders of blood glucose metabolism during pregnancy can increase the risk of adverse pregnancy outcomes, such as pregnancy-related hypertension, preeclampsia, eclampsia, miscarriage, macrosomia, and neonatal hypoglycemia. Continuous glucose monitoring (CGM) can safely and effectively monitor blood glucose changes in patients with gestational hyperglycemia, thereby reducing adverse pregnancy outcomes. Hence, this article aimed to provide a comprehensive review of the progress and indications for using CGM in pregnant patients with diabetes. CGM can reduce blood glucose fluctuations and the occurrence of serious hypoglycemia and hyperglycemia events and can provide time in range (TIR). TIR is an important indicator of blood glucose level. Patients with a higher TIR during pregnancy have better gestational outcomes. [ABSTRACT FROM AUTHOR]

Ovulation disorder is the main cause of infertility in patients with polycystic ovarian syndrome (PCOS). By summarizing the literature, the author found that acupuncture showed certain curative effects and advantages in the treatment of PCOS infertility. In this paper, the effects of acupuncture on the ovulation disorder infertility in PCOS can be described from six different aspects. Acupuncture can adjust the hypothalamic-pituitary-ovarian axis to restore the new dynamic balance, correct hormone disorders, and improve ovarian function. Acupuncture can improve blood flow microcirculation, promote the absorption and dissipation of inflammation, improve chronic inflammation and reduce the inhibition of follicle development. Acupuncture can regulate the PI3K/Akt/m TOR autophagy signaling pathway, reduce the level of autophagy in ovarian granulosa cells, reduce follicular atresia and improve the polycystic changes of the ovary. Acupuncture can affect the Kisspeptin signaling pathway, reduce the expression level of Kisspeptin and promote the development and maturation of follicles. Acupuncture can balance and regulate the disorder of glucose and lipid metabolism in ovary, restore the internal environment of ovary, make cells proliferate and differentiate normally and facilitate the follicle development. Acupuncture can improve endometrial receptivity and increase pregnancy rate by regulating endometrial pinocytosis, integrin αVβ3, estrogen progesterone receptor, homeobox gene A10 and other small molecules. From these aspects, the paper aims to explore the possible mechanism and pathway of action in acupuncture treating ovulation disorder infertility in PCOS, in order to provide theoretical references for clinical treatment. The paper also puts forward some thoughts on the mechanism of acupuncture in the treatment of PCOS. It is expected that further research can be carried out to clarify the mechanism of acupuncture in the treatment of PCOS ovulation disorder infertility [ABSTRACT FROM AUTHOR]