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Patients with cystic fibrosis (CF) are at risk to develop CF related diabetes (CFRD) and subsequently even diabetic neuro- and/or vasculopathy. We sought to determine if there are typical signs of diabetes-related retinal alterations present in CF patients with preserved and impaired glycemic control. During routine annual examination CF patients were offered an additional 7-day period of real time continuous glucose monitoring (rtCGM) and an ophthalmological examination including retinal optical coherence tomography (OCT). Patients were categorized according to the glycemic control, i.e. the results of an oral glucose tolerance test (OGTT) and rtCGM were taken into consideration. OCT data was analyzed by our previously published visual analysis software generating dedicated and spatially resolved deviation maps for visualization and quantification of differences in total retinal thickness and thickness of retinal nerve fiber layer (RNFL) as well as ganglion cell layer (GCL) in comparison to age-matched healthy controls and patients with either type 1 or type 2 diabetes mellitus. Results of the rtCGM and/or OGTT enabled discrimination between patients with normal glycemic control (CFNG; n = 6), with abnormal glycemic control (CFAG; n = 6) and overt CFRD (n = 4). OCT data indicates gradually increasing retinal thinning in all 3 groups, depending on the degree of glucose metabolism disorder compared to healthy controls. At the foveal region total retinal thickness and GCL thickness were significantly thinner in CFRD patients compared to CFNG patients (total retinal thickness: 260.4 µm (239.3–270.8) vs. 275.4 µm (254.3–289.5); GCL: 11.82 µm (11.16–15.25) vs. 17.30 µm (13.95–19.82); each p < 0.05). Although we investigated a rather small number of patients, we obtained evidence that intraretinal neurodegenerative changes occur in each of our subgroups (CFNG, CFAG, CFRD). Beyond this, our results favor the detrimental role of additional diabetes, as the deviations from healthy controls were most pronounced in the CFRD group and are similar to those seen in patients suffering from type 1 or type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Circulating atherogenic index of plasma (AIP) levels has been proposed as a novel biomarker for dyslipidemia and as a predictor of insulin resistance (IR) risk. However, the association between AIP and the incidence of new-onset stroke, particularly in individuals with varying glucose metabolism status, remains ambiguous. Methods: A total of 8727 participants aged 45 years or older without a history of stroke from the China Health and Retirement Longitudinal Study (CHARLS) were included in this study. The AIP was calculated using the formula log [Triglyceride (mg/dL) / High-density lipoprotein cholesterol (mg/dL)]. Participants were divided into four groups based on their baseline AIP levels: Q1 (AIP ≤ 0.122), Q2 (0.122 < AIP ≤ 0.329), Q3 (0.329 < AIP ≤ 0.562), and Q4 (AIP > 0.562). The primary endpoint was the occurrence of new-onset stroke events. The Kaplan–Meier curves, multivariate Cox proportional hazard models, and Restricted cubic spline analysis were applied to explore the association between baseline AIP levels and the risk of developing a stroke among individuals with varying glycemic metabolic states. Results: During an average follow-up of 8.72 years, 734 participants (8.4%) had a first stroke event. The risk for stroke increased with each increasing quartile of baseline AIP levels. Kaplan–Meier curve analysis revealed a significant difference in stroke occurrence among the AIP groups in all participants, as well as in those with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (all P values < 0.05). After adjusting for potential confounders, the risk of stroke was significantly higher in the Q2, Q3, and Q4 groups than in the Q1 group in all participants. The respective hazard ratios (95% confidence interval) for stroke in the Q2, Q3, and Q4 groups were 1.34 (1.05–1.71), 1.52 (1.19–1.93), and 1.84 (1.45–2.34). Furthermore, high levels of AIP were found to be linked to an increased risk of stroke in both pre-diabetic and diabetic participants across all three Cox models. However, this association was not observed in participants with normal glucose regulation (NGR) (p > 0.05). Restricted cubic spline analysis also demonstrated that higher baseline AIP levels were associated with higher hazard ratios for stroke in all participants and those with glucose metabolism disorders. Conclusions: An increase in baseline AIP levels was significantly associated with the risk of stroke in middle-aged and elderly individuals, and exhibited distinct characteristics depending on the individual's glucose metabolism status. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in the world, which begins with liver lipid accumulation and is associated with metabolic syndrome. Also, the name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). We performed focused drug screening and found that Cilostazol effectively ameliorated hepatic steatosis and might offer potential for NAFLD treatment. Our aim was to investigate the therapeutic effects of Cilostazol on the glycolipid metabolism and intestinal flora in NAFLD mice and explore the specific mechanism. In this study, 7-week-old male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce NAFLD, and then treated with intragastric administration for 12 weeks. The results showed that Cilostazol inhibited liver lipid de novo synthesis by regulating the AMPK-ACC1/SCD1 pathway and inhibited liver gluconeogenesis by the AMPK-PGC1α-G6P/PEPCK pathway. Cilostazol improved the intestinal flora diversity and intestinal microbial composition in the NAFLD mice, and specifically regulated Desulfovibrio and Akkermansia. In addition, Cilostazol increased the level of short-chain fatty acids in the NAFLD mice to a level similar to that in the blank Control group. Cilostazol reduces liver lipid accumulation in NAFLD mice by improving glucose and lipid metabolism disorders and intestinal dysfunction, thereby achieving the purpose of treating NAFLD. [ABSTRACT FROM AUTHOR]

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]

The circadian timing system controls glucose metabolism in a time‐of‐day dependent manner. In mammals, the circadian timing system consists of the main central clock in the bilateral suprachiasmatic nucleus (SCN) of the anterior hypothalamus and subordinate clocks in peripheral tissues. The oscillations produced by these different clocks with a period of approximately 24‐h are generated by the transcriptional‐translational feedback loops of a set of core clock genes. Glucose homeostasis is one of the daily rhythms controlled by this circadian timing system. The central pacemaker in the SCN controls glucose homeostasis through its neural projections to hypothalamic hubs that are in control of feeding behavior and energy metabolism. Using hormones such as adrenal glucocorticoids and melatonin and the autonomic nervous system, the SCN modulates critical processes such as glucose production and insulin sensitivity. Peripheral clocks in tissues, such as the liver, muscle, and adipose tissue serve to enhance and sustain these SCN signals. In the optimal situation all these clocks are synchronized and aligned with behavior and the environmental light/dark cycle. A negative impact on glucose metabolism becomes apparent when the internal timing system becomes disturbed, also known as circadian desynchrony or circadian misalignment. Circadian desynchrony may occur at several levels, as the mistiming of light exposure or sleep will especially affect the central clock, whereas mistiming of food intake or physical activity will especially involve the peripheral clocks. In this review, we will summarize the literature investigating the impact of circadian desynchrony on glucose metabolism and how it may result in the development of insulin resistance. In addition, we will discuss potential strategies aimed at reinstating circadian synchrony to improve insulin sensitivity and contribute to the prevention of type 2 diabetes. [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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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: 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]

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]

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]

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]

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]

Objective: To investigate the relationship between serum cortistatin (CST), sortilin, human leukocyte antigen-G (HLA-G) and glucose metabolism disorder, insulin resistance in patients with gestational diabetes mellitus (GDM) and their effect on pregnancy outcome. Methods: 333 cases of patients with GDM who were admitted to our hospital from June 2019 to May 2021 were selected as the study group, and 42 cases of healthy pregnant women with normal gestational glucose tolerance during the same period were selected as the control group. Glucose metabolism indexes, insulin resistance indexes, and serum CST, sortilin, and HLA-G levels of subjects were compared between the two groups. The correlation between glucose metabolism, insulin resistance indexes and serum CST, sortilin and HLA-G levels was analyzed by Pearson correlation analysis method. The patients with GDM were divided into poor outcome group and good outcome group according to the pregnancy outcome during the follow-up period, and the differences in serum CST, sortilin, HLA-G levels and clinical data were compared between the two groups, and Logistic regression analysis was used to determine the risk factors for poor pregnancy outcome in patients with GDM. Results: The proportion of family history of diabetes, complicated hyperlipidemia and the fasting plasma glucose (FPG), 1h postprandial blood glucose (1hPG), 2h postprandial blood glucose (2hPG), glycosylated hemoglobin (HbAlc), fasting insulin (FINS), insulin resistance index (HOMA-IR) and sortilin levels in the study group were higher than those in the control group (P＜0.05), and the serum CST and HLA-G levels in the study group were lower than those in the control group (P＜0.05). Serum CST and HLA-G of patients with GDM were negatively correlated with FPG, 2hPG, HbAlc, FINS, and HOMA-IR (P<0.05), and serum sortilin was positively correlated with FPG, 2hPG, HbAlc, FINS and HOMA-IR (P<0.05). The incidence of poor pregnancy outcome in the study group was 15.32%. The proportion of age ≥35 years old, 1 month before pregnancy body mass index (BMI) ≥24 kg/m², adverse pregnancy history, family history of diabetes, complicated hyperlipidemia, poor blood glucose control and serum sortilin level in the poor outcome group were higher than those in the good outcome group, and serum CST and HLA-G levels were lower than those in the good outcome group (P<0.05). Logistic regression analysis showed that age ≥35 years old, 1 month before pregnancy BMI ≥24 kg/m², poor blood glucose control, low serum CST level, high serum sortilin level and low serum HLA-G level were risk factors for poor pregnancy outcome in patients with GDM (P＜0.05). Conclusion: Serum CST, sortilin and HLA-G in patients with GDM are closely related to glucose metabolism disorder, insulin resistance and poor pregnancy outcome, suggesting that while strengthening blood glucose monitoring and control, the detection of serum CST, sortilin and HLA-G is helpful for evaluating the condition of patients with GDM and predicting the risk of poor pregnancy outcome. Objective: To investigate the relationship between serum cortistatin (CST), sortilin, human leukocyte antigen-G (HLA-G) and glucose metabolism disorder, insulin resistance in patients with gestational diabetes mellitus (GDM) and their effect on pregnancy outcome. Methods: 333 cases of patients with GDM who were admitted to our hospital from June 2019 to May 2021 were selected as the study group, and 42 cases of healthy pregnant women with normal gestational glucose tolerance during the same period were selected as the control group. Glucose metabolism indexes, insulin resistance indexes, and serum CST, sortilin, and HLA-G levels of subjects were compared between the two groups. The correlation between glucose metabolism, insulin resistance indexes and serum CST, sortilin and HLA-G levels was analyzed by Pearson correlation analysis method. The patients with GDM were divided into poor outcome group and good outcome group according to the pregnancy outcome during the follow-up period, and the differences in serum CST, sortilin, HLA-G levels and clinical data were compared between the two groups, and Logistic regression analysis was used to determine the risk factors for poor pregnancy outcome in patients with GDM. Results: The proportion of family history of diabetes, complicated hyperlipidemia and the fasting plasma glucose (FPG), 1h postprandial blood glucose (1hPG), 2h postprandial blood glucose (2hPG), glycosylated hemoglobin (HbAlc), fasting insulin (FINS), insulin resistance index (HOMA-IR) and sortilin levels in the study group were higher than those in the control group (P＜0.05), and the serum CST and HLA-G levels in the study group were lower than those in the control group (P＜0.05). Serum CST and HLA-G of patients with GDM were negatively correlated with FPG, 2hPG, HbAlc, FINS, and HOMA-IR (P<0.05), and serum sortilin was positively correlated with FPG, 2hPG, HbAlc, FINS and HOMA-IR (P<0.05). The incidence of poor pregnancy outcome in the study group was 15.32%. The proportion of age ≥35 years old, 1 month before pregnancy body mass index (BMI) ≥24 kg/m², adverse pregnancy history, family history of diabetes, complicated hyperlipidemia, poor blood glucose control and serum sortilin level in the poor outcome group were higher than those in the good outcome group, and serum CST and HLA-G levels were lower than those in the good outcome group (P<0.05). Logistic regression analysis showed that age ≥35 years old, 1 month before pregnancy BMI ≥24 kg/m², poor blood glucose control, low serum CST level, high serum sortilin level and low serum HLA-G level were risk factors for poor pregnancy outcome in patients with GDM (P＜0.05). Conclusion: Serum CST, sortilin and HLA-G in patients with GDM are closely related to glucose metabolism disorder, insulin resistance and poor pregnancy outcome, suggesting that while strengthening blood glucose monitoring and control, the detection of serum CST, sortilin and HLA-G is helpful for evaluating the condition of patients with GDM and predicting the risk of poor pregnancy outcome. [ABSTRACT FROM AUTHOR]

Obesity, diabetes, and cardiovascular diseases are the major chronic metabolic diseases that threaten human health. In order to combat these epidemics, there remains a desperate need for effective, safe, and easily available therapeutic strategies. Recently, the development of natural product research has provided new methods and options for these diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are key regulators of metabolic diseases, and natural products can improve lipid and glucose metabolism disorders and cardiovascular diseases by regulating the expression of miRNAs. In this review, we present the recent advances involving the associations between miRNAs and natural products and the current evidence showing the positive effects of miRNAs for natural product treatment in metabolic diseases. We also encourage further research to address the relationship between miRNAs and natural products under physiological and pathological conditions, thus leading to stronger support for drug development from natural products in the future. [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]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Endocrine disruptors are chemicals that can interfere and interact with the endocrine system, resulting in altered hormonal signaling and function. PBDEs are common endocrine disruptors that have been commonly used in industrial products, and their environmental accumulation has become a rising concern. Human exposure to PBDEs has been shown to influence glucose metabolism, thyroid and ovarian function and potentially affect cancer risk. Evidence, however, is often conflicting. This narrative review provides a comprehensive overview of the potential role of PBDEs in human health, with a particular focus on glucose metabolism, endocrine diseases and cancer. A deeper understanding of the complex interplay between exposure to endocrine disruptors, on one side, and obesity, diabetes, related metabolic disturbances and cancer, on the other side, can help guide public health interventions, in order to reduce the burden of these major social threats. There is increasing evidence of the role of endocrine disruptors (EDs) derived from commonly employed compounds for manufacturing and processing in altering hormonal signaling and function. Due to their prolonged half-life and persistence, EDs can usually be found not only in industrial products but also in households and in the environment, creating the premises for long-lasting exposure. Polybrominated diphenyl ethers (PBDEs) are common EDs used in industrial products such as flame retardants, and recent studies are increasingly showing that they may interfere with both metabolic and oncogenic pathways. In this article, a multidisciplinary panel of experts of the Italian Association of Medical Diabetologists (AMD), the Italian Society of Diabetology (SID), the Italian Association of Medical Oncology (AIOM), the Italian Society of Endocrinology (SIE) and the Italian Society of Pharmacology (SIF) provides a review on the potential role of PBDEs in human health and disease, exploring both molecular and clinical aspects and focusing on metabolic and oncogenic pathways. [ABSTRACT FROM AUTHOR]

Diabetes-related muscle damage has been overlooked despite its known association with increased morbidity and mortality in DM individuals. PBMT is a recognized alternative to improve skeletal muscle health in other populations, but its effectiveness in DM is still unclear. To address this issue, we reviewed preclinical studies, available in any language and period, in ten sources of information. The methods were previously registered at PROSPERO (CRD42021271041), based on PRISMA recommendations. Studies in murine models of T1DM or T2DM that reported quantitative analyses of skeletal muscles treated with low-level light therapy could be included after a blind selection process. Most of the seven included studies focus on decompensated T1DM rats with acute muscle injury (cryoinjury or contusion). In these five studies, PBMT improved muscle regeneration, by reducing inflammation and stimulating factors pro-angiogenesis and pro-myogenesis. Some positive effects could also be observed in two studies on muscles without acute injury: control of oxidative stress (T1DM) and reduction of myosteatosis (T2DM). Although infrared laser applied locally appears to be a promising approach, optimal parameters are undefined due to the heterogeneity of outcomes and high risk of bias, which prevented a quantitative synthesis. Several aspects of this growing field have yet to be investigated, particularly regarding the DM model (e.g., aged animals, T2DM), intervention (e.g., comparison with LED), and outcomes (e.g., muscle mass, strength, and function). Future research should aim to improve the internal validity by following guidelines for animal studies and enhance the translatability to clinical trials by using animal models that closely mimic patients with DM in rehabilitation settings. [ABSTRACT FROM AUTHOR]

Background: Changes in vascular function are closely associated with the development of cardiovascular disease (CVD). Pulse wave velocity (PWV) is a potential indicator of vascular dysfunction; it allows noninvasive assessment of arterial stiffness. Currently, evidence for the effects of different classes of antidiabetic drugs on arterial stiffness remains limited. In this study, a network meta‐analysis (NMA) was performed to explore the associations between changes in arterial stiffness and first‐line antidiabetic drugs by evaluating PWV in patients with different metabolic abnormalities. Methods: We systematically searched several electronic databases for randomized controlled trials (RCTs) published from inception until 25 August 2022, without language restrictions. The primary outcome was the change in PWV (ΔPWV) in all included studies; subgroup analysis was performed for patients with abnormal glucose metabolism, including prediabetes and diabetes mellitus. NMA was performed to calculate the mean differences (MDs) with 95% confidence intervals (CIs) as effect sizes to evaluate the ΔPWV. Results: Among the 2257 candidate articles identified in the initial search, 18 RCTs were eventually included in the analysis. In all studies, two classes of new antidiabetic drugs, glucagon‐like peptide‐1 receptor (GLP‐1R) agonists and sSodium‐glucose co‐transporter 2 (SGLT‐2) inhibitors, improved arterial stiffness by decreasing PWV compared with placebo (MD = −1.11, 95% CI: −1.94 to 0.28) and (MD = −0.76, 95% CI: −1.45 to −0.08). A conventional antidiabetic drug, metformin, also showed similar efficacy compared with placebo (MD = −0.73, 95% CI: −1.33 to −0.12). Finally, in subgroup studies of patients with abnormal glucose metabolism diseases, GLP‐1R agonists (MD = −1.06, 95% CI: −2.05 to −0.10) significantly decreased PWV compared with placebo. Conclusion: Three classes of antidiabetic drugs—GLP‐1R agonists, SGLT‐2 inhibitors, and metformin—have the potential to improve arterial stiffness. Among the six classes of antidiabetic drugs analyzed, GLP‐1R agonists constitute the only class of drugs that improves arterial stiffness in patients with abnormal glucose metabolism diseases. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis of hospitalized elderly patients with infectious stress hyperglycaemia (ISH) is clinically important, especially under the global coronavirus disease 2019 (COVID-19) pandemic, as without timely prevention and effective treatment, it is likely to deteriorate into septic shock, thus worsening patient survival and complications. Moreover, cumulative studies have showed that patients with COVID-19 are reported to have a greater prevalence of hyperglycaemia. However, the underlying mechanism remained unknown. Aim and method: Systematic screening of specific biomarkers of serum exosome-derived microRNAs (sE-miRNAs) from ISH patient has not yet been reported. In this study, sE-miRNAs were derived from 10 elderly patients with ISH and 5 control patients with disease-match without hyperglycaemia (non-ISH). RNA sequencing identified that a total number of 49 sE-miRNAs with differential expression between ISH and control group.Ofwhich, top 22miRNAs ranked by sensitivity x specificity were chosen for further research. Moreover, 7 out of 22 miRNAs that related to glucose metabolism or immune disorder were picked up for further validation in an independent cohort consisting of 52 participants (31 ISH and 21 non-ISH). Result: A validation analysis revealed that three miRNAs (hsa-miR-21-5p, hsamiR- 335-5p and hsa-miR-28-3p) were statistically up-regulated in exosomes from ISH patients. In the validation cohort and discovery cohort, the AUC of three individual miRNAs ranged from 0.73 to 0.88. A logistic model combining three miRNAs achieved an AUC of 0.96. Besides, sE-miRNAs-based signatures effectively characterized patients' poor clinical outcome. Survival curve analysis showed that hsa-miR-335-5p, hsa-miR-28-3p but not hsa-miR-21-5p, were significantly closely related to mortality, and the combination of these three miRNAs could also predict patients outcome (p < .05). Conclusion: This study depicted the circulating exosomal miRNAs change in ISH patient, which could be used as a promising biomarker to detect ISH at an early stage and predict patients clinical outcome. [ABSTRACT FROM AUTHOR]

Cyclocarya paliurus (CP) contains triterpene acids that can improve glucose and lipid metabolism disorders. However, controlling the composition and content of these active ingredients in CP extracts is challenging. The main active components in CP triterpene acids, including ursolic acid (UA), oleanolic acid (OA), and betulinic acid (BA), exhibit antihyperglycemic and antihypertensive effects. The response surface methodology was utilized to design and optimize the ratio of UA, OA, and BA based on the inhibition rate of pancrelipase and α-amylase. The proportional mixture of UA, OA, and BA resulted in the formation of a complex known as Cyclocarya paliurus triterpenoid acid (TAC). Se-methylselenocysteine (MSC), a compound with various physiological functions such as antioxidant properties and tumor inhibition, has been used in combination with TAC to form the TAC/MSC complex. Our data demonstrate that TAC/MSC improved palmitic acid (PA)-induced insulin resistance in HepG2 cells through activating the phosphoinositide 3-kinase (PI3K) /protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) pathway. Moreover, TAC/MSC effectively improved hyperglycemia, glucose intolerance, insulin resistance, and lipid metabolism disorder in mice with type 2 diabetes mellitus (T2DM), attenuated hepatic steatosis, and reduced oxidative stress to alleviate T2DM characteristics. [ABSTRACT FROM AUTHOR]

Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, glucagon-like peptide-1 receptor agonists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aim to investigate how the GLP-1RA exendin-4 (Ex-4) affects the microRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from control, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment pathway analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, insulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigation. [ABSTRACT FROM AUTHOR]

Glycosylphosphatidylinositol‐specific phospholipase D (GPLD1) is a specific enzyme for glycosylphosphatidylinositol (GPI) anchors, thereby exerting its biological functions by cleaving membrane‐associated GPI molecules. GPLD1 is abundant in serum, with a concentration of approximately 5−10 µg/mL. Previous studies have demonstrated that GPLD1 plays a crucial role in the pathogenesis of numerous chronic diseases including disorders of lipid and glucose metabolism, cancer, and neurological disorders. In the present study, we reviewed the structure, functions, and localization of GPLD1 in chronic diseases, as well as exercise‐mediated regulation of GPLD1, thus providing a theoretical support to develop GPLD1 as a new therapeutic target for chronic diseases. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a very common disease whose initial diagnosis is mainlymade by general practitioners. As this is often done in asymptomatic individuals on the basis of laboratory values alone, and both the analysis and the pre-analysis are influenced by many factors, there is a high risk of both over- and underdiagnosis. In addition, it should be possible to integrate the necessary examinations into daily practice with little effort. The new chapter on "Epidemiology and diagnosis" in the National Treatment Guideline for Type 2 DiabetesMellitus therefore contains an algorithm that should enable general practitioners and their practice teams to identify people with type 2 diabetes mellitus who should be treated and, on the other hand, to avoid harming and stigmatising people who are actually healthy by overdiagnosing them. Particular attention is paid to the limitations of laboratory values. In addition, screening for relevant diabetes-associateddiseases and diabetic complications should pragmatically be carried out at the time of initial diagnosis. [ABSTRACT FROM AUTHOR]

Background: Neuregulin-4 (Nrg4), a novel brown fat-enriched factor, has been reported to play a crucial role in developing metabolic disorders. The current case-control study aimed to investigate the association between serum Nrg4 and coronary artery disease (CAD). Methods: This study enrolled 43 patients with CAD and 43 subjects with normal coronary arteries diagnosed by coronary angiography. Anthropometric and biochemical parameters were measured and recorded. The serum Nrg4 level was determined using the enzyme-linked immunosorbent assay. The relationships between circulating Nrg4 and CAD and other clinical parameters were analyzed. A receiver operating characteristic analysis was applied to assess the utility of Nrg4 in identifying CAD. Results: The study population comprised 86 patients, including 64 men (74.4%), at a mean age of 57.83±6.01 years. Patients with CAD had significantly lower serum Nrg4 than the control group (P<0.001). The serum Nrg4 level was negatively correlated with anthropometric variables, including the body mass index, waist circumference, and the waist-to-hip ratio, fasting blood glucose, and the triglyceride-glucose index (P<0.05). In multivariable-adjusted regression analysis, the odds of CAD decreased by 46% per 1 SD elevation in the serum Nrg4 level (OR, 0.54; 95% CI, 0.40 to 0.73; P<0.001) after controlling for potential confounders. Nrg4 showed a significantly high area under the curve value (AUC, 0.85; 95% CI, 0.75 to 0.94) with 81.4% sensitivity and 95.3% specificity to identify CAD. Conclusion: Generally, the serum level of Nrg4 declines in patients with CAD, which might be an independent risk factor for CAD. [ABSTRACT FROM AUTHOR]

Diabetes and cancer are among the most frequently cited causes of disability worldwide. The pathomechanism of glycemia disorders and carcinogenesis have common features that drive each other. Diabetes is estimated to be present in 8–18% of cancer patients. Hyperglycemia and its consequences are associated with an increased risk of cancer development, disease progression, and an increased risk of death. Treatment of glucose metabolism disorders requires an individual approach regarding nutrition and lifestyle. [ABSTRACT FROM AUTHOR]

Older patients are prone to multimorbidity or related polypharmacy, which may cause various adverse drug reactions (ADRs) and a high incidence of drug‐related health problems. Although not often noted, ADRs include nutrition‐related adverse reactions. Aging, multiple illnesses, mental and psychological problems, declining physical function, and environmental factors can lead to decreased food intake and increased metabolic stress in older people, resulting in energy imbalances that cause malnutrition. ADRs can lead to appetite loss, followed by decreased food intake, which in turn causes malnutrition and deficiencies of various nutrients. However, these nutrition‐related ADRs have received less attention. This review article describes drug–nutrition interactions, with a particular focus on older patients. Geriatr Gerontol Int 2023; 23: 465–477. Pharmacotherapy is a very important means of disease prevention and treatment for older patients. However, adverse drug reactions can have a significant negative impact on the health of older people. In this paper, the impact of drug therapy on nutritional status, dietary intake, the absorption and excretion of nutrients, and metabolism, with a focus on older people, is reviewed. [ABSTRACT FROM AUTHOR]

Prediabetes is a transitional state between normal blood glucose levels and diabetes, but it is also a reversible process. At the same time, as one of the most important tissues in the human body, the metabolic disorder of skeletal muscle is closely related to prediabetes. Huidouba (HDB) is a clinically proven traditional Chinese medicine with significant effects in regulating disorders of glucose and lipid metabolism. Our study aimed to investigate the efficacy and mechanism of HDB in prediabetic model mice from the perspective of skeletal muscle. C57BL/6J mice (6 weeks old) were fed a high-fat diet (HFD) for 12 weeks to replicate the prediabetic model. Three concentrations of HDB were treated with metformin as a positive control. After administration, fasting blood glucose was measured as an indicator of glucose metabolism, as well as lipid metabolism indicators such as total triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), free fatty acid (FFA), and lactate dehydrogenase (LDH). Muscle fat accumulation and glycogen accumulation were observed. The protein expression levels of p-AMPK, AMPK, PGC-1α, PPAR-α, and GLUT-4 were detected. After HDB treatment, fasting blood glucose was significantly improved, and TG, LDL-C, FFA, and LDH in serum and lipid accumulation in muscle tissue were significantly reduced. In addition, HDB significantly upregulated the expression levels of p-AMPK/AMPK, PGC-1α, PPAR-α, and GLUT-4 in muscle tissue. In conclusion, HDB can alleviate the symptoms of prediabetic model mice by promoting the AMPK/PGC-1α/PPARα pathway and upregulating the expression of GLUT-4 protein. [ABSTRACT FROM AUTHOR]

The global prevalence of overweight and obesity has dramatically increased in the last few decades, with a significant socioeconomic burden. In this narrative review, we include clinical studies aiming to provide the necessary knowledge on the role of the gut microbiota in the development of diabetic pathology and glucose-metabolism-related disorders. In particular, the role of a certain microbial composition of the fermentative type seems to emerge without a specific link to the development in certain subjects of obesity and the chronic inflammation of the adipose tissues, which underlies the pathological development of all the diseases related to glucose metabolism and metabolic syndrome. The gut microbiota plays an important role in glucose tolerance. Conclusion. New knowledge and new information is presented on the development of individualized therapies for patients affected by all the conditions related to reduced glucose tolerance and insulin resistance. [ABSTRACT FROM AUTHOR]

Existing research has suggested that depression results in disorders of glucose metabolism in the organism which causing insufficient energy supply. However, the overall changes in glucose metabolism that arise from depression have not been clarified. In this study, the depression-like behavior in chronically unpredictable mild stressed rats was investigated, and the fate of glucose was tracked through isotope tracing and mass spectrometry, with a focus on metabolite changes in cecal contents. As indicated by the results, the isotopic results of cecal contents can indicate the metabolic end of the organism. Moreover, the TCA cycle activity was notably reduced, and the gluconeogenesis pathway was abnormally up-regulated in the CUMS-induced rats. The organism expedited other glucose metabolism pathways to make up for the insufficiency of energy. As a result, the activity of the inefficient glycolysis pathway was increased. Existing research has only investigated the metabolism of 13C-glucose, and lipids and proteins have been rarely explored. The chronic unpredictable mild stress can inhibit the entry of pyruvate into mitochondria in SD rats, such that the activity of TCA is reduced, and insufficient energy supply is caused. The organism is capable of expediting other glucose metabolism rate pathways to make up for the insufficiency of energy, whereas it still cannot compensate for the loss of energy. As a result, CUMS-induced rats exhibited high-rate and low-efficiency glucose metabolism. [Display omitted] • Stable isotope tracer metabolomics revealed the glucose metabolism disorder caused by depression in CUMS-induced rats. • Blocked TCA cycle leads to an increase in the activity of inefficient glucose metabolic pathways. • The overall glucose metabolism caused by depression is characterized by high rate and low efficiency. • Improving the overall glucose metabolism caused by depression is a potential method to treat depression. [ABSTRACT FROM AUTHOR]

Background: Considering the strong correlation made between Alzheimer's disease (AD) and the pathology of glucose metabolism disorder, we sought to analyze the effects of fasting blood glucose (FBG) level, fasting plasma insulin (FINS) level, and insulin resistance index (HOMA-IR) on the risk and severity of AD.Objective: Reveal the pathological relationship between AD and insulin resistance.Methods: We searched 5 databases from inception through April 4, 2022. Meta-regression was conducted to identify if there were significant differences between groups. Shapiro-Wilk test and the Q-Q diagram were applied to evaluate the normality of variables. A multiple logistic regression model was employed to explore the association between FBG, FINS, HOMA-IR, and Mini-Mental State Examination scale score (MMSE).Results: 47 qualified articles including 2,981 patients were enrolled in our study. FBG (p < 0.001), FINS (p < 0.001), and HOMA-IR (p < 0.001) were higher in AD patients than in controls. HOMA-IR was negatively correlated with MMSE (p = 0.001) and positively related to the sex ratio (male versus female) (p < 0.05). HOMA-IR obeyed lognormal distribution (p > 0.05), and the 95% bilateral boundary values were 0.73 and 10.67. FBG (p = 0.479) was positively correlated to MMSE, while FINS (p = 0.1657) was negatively correlated with MMSE.Conclusion: The increase in the levels of FBG, FINS, and HOMA-IR served as precise indicators of the risk of AD. HOMA-IR was found to be correlated to the increasing severity of AD, especially in male AD patients. [ABSTRACT FROM AUTHOR]

Aims: Several trials have assessed the antihyperglycemic effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) in patients with type 2 diabetes mellitus (T2DM). We conducted a quantitative analysis to assess the effects of SGLT2Is on renal risk factors in patients with abnormal glucose metabolism. Materials and methods: Randomized controlled trials (RCTs) were identified by searching the PubMed, Embase, Scopus, and Web of Science databases published before September 30, 2022. The intervention group received SGLT2Is as monotherapy or add-on treatment, and the control group received placebos, standard care, or active control. Risk of bias assessment was performed using the Cochrane risk of bias assessment tool. Meta-analysis was performed on studies with abnormal glucose metabolism populations and studies using the weighted mean differences (WMDs) as the measure of the effect size. Clinical trials providing changes in serum uric acid (SUA) were included. The mean change of SUA, glycated hemoglobin (HbA1c), body mass index (BMI), and estimated glomerular filtration rate (eGFR) were calculated. Results: After a literature search and detailed evaluation, a total of 11 RCTs were included for quantitative analysis to analyze the differences between the SGLT2I group and the control group. The results showed that SGLT2I significantly reduced SUA (MD = −0.56, 95% CI = −0.66 ~ −0.46, I2 = 0%, P < 0.00001), HbA1c (MD = −0.20, 95% CI = −0.26 ~ −0.13, I2 = 0%, P < 0.00001), and BMI (MD = −1.19, 95% CI = −1.84 ~ −0.55, I2 = 0%, P = 0.0003). There was no significant difference in the reduction of eGFR observed in the SGLT2I group (MD = −1.60, 95% CI = −3.82 ~ 0.63, I2 = 13%, P = 0.16). Conclusions: These results showed that the SGLT2I group caused greater reductions in SUA, HbA1c, and BMI but had no effect on eGFR. These data suggested that SGLT2Is may have numerous potentially beneficial clinical effects in patients with abnormal glucose metabolism. However, these results need to be consolidated by further studies. [ABSTRACT FROM AUTHOR]

Purpose: This study was aimed to evaluate the effect of dapagliflozin as add-on medication to short-term intensive insulin therapy on β-cell function in newly diagnosed type 2 diabetes mellitus (T2DM) patients. Methods: Sixty participants were recruited and randomized to receive either multiple daily insulin injections alone (MDI group), receiving pre-meal insulin aspart and insulin glargine at bedtime, or in combination with dapagliflozin 10 mg per day (MDI+DAPA group). Data was collected at baseline (d0), 14 days after reaching euglycemia (D14), and at the 12-week visit (W12). Fasting C-peptide concentration, areas under the curve (AUC) for C-peptide (CP) and insulin (INS), homeostasis model assessment (HOMA) indices, early insulin secretion index (EISI), and glycemic control were compared before and after treatment. Results: The two groups achieved euglycemia in similar time. Daily average insulin dosage in the MDI+DAPA group (0.27 ± 0.12 U/kg·day, n = 28) was lower than that in the MDI group (0.36 ± 0.22 U/kg·day, n = 29) (p = 0.050). HbA1c and plasma glucose were significantly decreased after treatment but of no significant difference between the two groups. Proportions of patients who achieved HbA1c ≤ 6.5% were similar (58.6% in the MDI group vs. 53.6% in the MDI+DAPA group, p = 0.701). Fasting C-peptide elevated after treatment but were comparable in the two groups. Both groups obtained similar improvements of AUC-CP, AUC-INS, HOMA-β, EISI, and HOMA-IR. Conclusion: Dapagliflozin as add-on could reduce daily insulin dosage, but bring no additive effect in improving β-cell function for newly diagnosed T2DM patients receiving intensive insulin therapy. Trial registration: The study was approved by the Chinese Clinical Trial Registry (ChiCTR.org.cn: ChiCTR1800015822). [ABSTRACT FROM AUTHOR]

Comorbid glucose metabolism abnormalities are very common in patients with major depressive disorder (MDD), and glucose metabolism and lipid metabolism are closely related. However, there are few researches on the incidence and related factors of lipid metabolism abnormalities among MDD patients with comorbid glucose metabolism abnormalities. A cross-sectional study involving 1718 first-episode and drug-naïve (FEDN) MDD patients was conducted. The 17-item Hamilton Depression Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAMA) and Positive and Negative Syndrome Scale (PANSS) positive subscale were utilized to evaluate depressive, anxiety and psychotic symptom, respectively. Serum thyroid function-related parameters, glucose- and lipid-metabolism parameters were measured. The prevalence of abnormal lipid metabolism was significantly higher in FEDN MDD patients with abnormal glucose metabolism than in those without abnormal glucose metabolism (P < 0.001). In MDD patients with abnormal glucose metabolism, TSH, FT3 and body mass index (BMI) levels were significantly higher in the abnormal lipid metabolism subgroup than in the non-abnormal lipid metabolism subgroup. Binary logistic regression analysis showed that TSH, FT3 and BMI were the influencing factors of abnormal lipid metabolism in MDD patients with abnormal glucose metabolism (all P < 0.05). MDD patients with abnormal glucose metabolism have a high prevalence of abnormal lipid metabolism. Moreover, abnormal glucose metabolism was an independent risk factor for abnormal lipid metabolism in patients with MDD. In addition, thyroid hormone function and BMI may contribute to the co-occurrence of abnormal lipid metabolism in MDD patients with abnormal glucose metabolism. [ABSTRACT FROM AUTHOR]

The DOHaD theory suggests that adverse environmental factors in early life may lead to the development of metabolic diseases including diabetes and hypertension in adult offspring through epigenetic mechanisms such as DNA methylation. Folic acid (FA) is an important methyl donor in vivo and participates in DNA replication and methylation. The preliminary experimental results of our group demonstrated that lipopolysaccharide (LPS, 50 µg/kg/d) exposure during pregnancy could lead to glucose metabolism disorders in male offspring, but not female offspring; however, the effect of folic acid supplementation on glucose metabolism disorders in male offspring induced by LPS exposure remains unclear. Therefore, in this study, pregnant mice were exposed to LPS on gestational day (GD) 15–17 and were given three doses of FA supplementation (2 mg/kg, 5 mg/kg, or 40 mg/kg) from mating to lactation to explore its effect on glucose metabolism in male offspring and the potential mechanism. This study confirmed that FA supplementation of 5 mg/kg in pregnant mice improved glucose metabolism in LPS-exposed offspring during pregnancy by regulating gene expression. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) has revolutionized the field of genomics and created new opportunities for basic research. We described the strategy for the NGS validation of the "dysglycaemia panel" composed by 44 genes related to glucose metabolism disorders (MODY, Wolfram syndrome) and familial renal glycosuria using Ion AmpliSeq technology combined with Ion-PGM. Anonymized DNA of 32 previously genotyped cases with 33 different variants were used to optimize the methodology. Standard protocol was used to generate the primer design, library, template preparation, and sequencing. Ion Reporter tool was used for data analysis. In all the runs, the mean coverage was over 200×. Twenty-nine out of thirty three variants (96.5%) were detected; four frameshift variants were missed. All point mutations were detected with high sensitivity. We identified three further variants of unknown significance in addition to pathogenic mutations previously identified by Sanger sequencing. The NGS panel allowed us to identify pathogenic variants in multiple genes in a short time. This could help to identify several defects in children and young adults that have to receive the genetic diagnosis necessary for optimal treatment. In order not to lose any pathogenic variants, Sanger sequencing is included in our analytical protocol to avoid missing frameshift variants. [ABSTRACT FROM AUTHOR]