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Prolactin, a hormone that has been studied for almost a century, has evolved from a reproductive regulator to a key player in metabolic health. Initially identified for its lactogenic role, the impact of prolactin on glucose and lipid metabolism became evident in the 1970s, leading to a paradigm shift in our understanding. Deviations in prolactin levels, including hyperprolactinaemia and hypoprolactinaemia, have been associated with adverse effects on glucose and lipid metabolism. Mechanistically, prolactin regulates metabolic homoeostasis by maintaining islet abundance, regulating the hypothalamic energy regulatory centre, balancing adipose tissue expansion, and regulating hepatic metabolism. Given the widespread use of pharmaceutical agents that affect prolactin levels, it is important to examine prolactin-related metabolic effects. Recently, a profound exploration of the intricate metabolic role of prolactin has been conducted, encompassing its rhythm-dependent regulatory influence on metabolism and its correlation with cognitive impairment associated with metabolic diseases. In this review, we highlight the role of prolactin as a metabolic regulator, summarise its metabolic effects, and discuss topics related to the association between prolactin and metabolic comorbidities., (© 2024 John Wiley & Sons Ltd.)

We report the novel finding of a widespread reduction in myocardial native T1 values and size of abnormal regions following gene therapy in a pediatric patient with infantile-onset Pompe disease. We emphasize the importance of serial cardiac magnetic resonance in assessing the efficacy of gene therapy and monitoring myocardial alterations in Pompe disease., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Ethnopharmacological Relevance: Mailuo Shutong Pill (MLST), a traditional Chinese medicine (TCM), has been widely used for clearing heat and detoxifying, eliminating stasis and dredging meridians, dispelling dampness and diminishing swelling. Earlier study found that MLST could improve cerebral ischemic-reperfusion injury, however, the potential mechanism has not been well evaluated., Aim of Study: In this study, a well established and widely used mice model of middle cerebral artery occlusion/reperfusion (MCAO/R) was preformed to evaluate the protective function of MLST on cerebral ischemic-reperfusion injury and further discuss the potential pharmacological mechanisms., Materials and Methods: Chemical profiling of MLST was analyzed based on Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry. ICR mice were challenged by MCAO/R surgery. The protective effect of MLST on MCAO/R injury was evaluated by neurological deficit score, cerebral infarct rate, brain water content, H&E and nissl staining. The blood-brain barrier (BBB) integrity was detected by Evans blue staining. The potential pharmacological mechanism of MLST in treating MCAO/R injury was further elucidated by the methods of proteomics, central carbon targeted metabolomics, as well as Western blot. Immunohistochemistry was used to detect the microglia infiltration, enzyme linked immunosorbent assay (ELISA) kit was explored to evaluate the content of IL-1β, TNF-α and IL-6 in brain tissue, and Western blot was used to detect proteins expression in brain tissue., Results: A total of 76 chemical compounds have been determined in MLST. MLST effectively protected mice from MCAO/R injury, which was confirmed by lower neurological deficit score, cerebral infarct rate, brain water content and nissl body loss, and improved brain pathology. Meanwhile, MLST upregulated the expression of ZO-1, Occludin and Claudin 5 by downregulating the ratio of TIMP1/MMP9 to suppress the entrance of Evans blue to brain tissue, indicating that MLST maintained the integrity of BBB. Further studies indicated that MLST inhibited the inflammatory level of brain tissue by inhibiting microglia infiltration and downregulating NLRP3 inflammasome signaling pathway. The results of proteomics, Western blot, and central carbon targeted metabolomics confirmed that MLST regulated Glycolysis/Gluconogenesis, Pyruvate metabolism and TCA cycle in brain tissue of mice with MCAO/R., Conclusion: MLST inhibits neuroinflammation by regulating glucose metabolism disorders to interfere with immune metabolism reprogramming and inhibit the NLRP3 inflammasome signaling pathway, and finally improve cerebral ischemia-reperfusion injury. This study confirms that MLST is a potential drug for treating Cerebral ischemic stroke., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2024 The Authors. Journal of Pineal Research published by John Wiley & Sons Ltd.)

Foodborne carbon dots (CDs) are generally produced during cooking and exist in food items. Generally, CDs are regarded as nontoxic materials, but several studies have gradually confirmed the cytotoxicity of CDs, such as oxidative stress, reduced cellular activity, apoptosis, etc. However, studies focusing on the health effects of long-term intake of food-borne CDs are scarce, especially in populations susceptible to metabolic disease. In this study, we reported that CDs in self-brewing beer had no effect on glucose metabolism in CHOW-fed mice but exacerbated high-fat-diet (HFD)-induced glucose metabolism disorders via the gut-liver axis. Chronic exposure to foodborne CDs increased fasting glucose levels and exacerbated liver and intestinal barrier damage in HFD-fed mice. The 16s rRNA sequencing analysis revealed that CDs significantly altered the gut microbiota composition and promoted lipopolysaccharide (LPS) synthesis-related KEGG pathways (superpathway of (Kdo)2-lipid A, Kdo transfer to lipid IVA Ill (Chlamydia), lipid IVA biosynthesis, and so on) in HFD-fed mice. Mechanically, CD exposure increased the abundance of Gram-negative bacteria ( Proteobacteria and Desulfovibrionaceae ), thus producing excessive endotoxin-LPS, and then LPS was transferred by the blood circulation to the liver due to the damaged intestinal barrier. In the liver, LPS promoted TLR4/NF-κB/P38 MAPK signaling, thus enhancing systemic inflammation and exacerbating HFD-induced insulin resistance. However, pretreating mice with antibiotics eliminated these effects, indicating a key role for gut microbiota in CDs exacerbating glucose metabolism disorders in HFD-fed mice. The finding herein provides new insight into the potential health risk of foodborne nanoparticles in susceptible populations by disturbing the gut-liver axis.

Exposure to arsenic during gestation has lasting health-related effects on the developing fetus, including an increase in the risk of metabolic disease later in life. Epigenetics is a potential mechanism involved in this process. Ten-eleven translocation 2 (TET2) has been widely considered as a transferase of 5-hydroxymethylcytosine (5hmC). Here, mice were exposed, via drinking water, to arsenic or arsenic combined with ascorbic acid (AA) during gestation. For adult offspring, intrauterine arsenic exposure exhibited disorders of glucose metabolism, which are associated with DNA hydroxymethylation reprogramming of hepatic nuclear factor 4 alpha (HNF4α). Further molecular structure analysis, by SEC-UV-DAD, SEC-ICP-MS, verified that arsenic binds to the cysteine domain of TET2. Mechanistically, arsenic reduces the stability of TET2 by binding to it, resulting in the decrease of 5hmC levels in Hnf4α and subsequently inhibiting its expression. This leads to the disorders of expression of its downstream key glucose metabolism genes. Supplementation with AA blocked the reduction of TET2 and normalized the 5hmC levels of Hnf4α, thus alleviating the glucose metabolism disorders. Our study provides targets and methods for the prevention of offspring glucose metabolism abnormalities caused by intrauterine arsenic exposure., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Neonatal encephalopathy (NE) is a diagnosis that is usually unexpected. Though there are many risk factors for the condition and multiple theories as to its genesis, the majority of cases cannot be predicted prior to the occurrence of the clinical syndrome. Indeed, it is common for a pregnant person to have multiple risk factors and a completely healthy child. Conversely, people with seemingly no risk factors may go on to have a profoundly affected child. In this synopsis we review risk factors, potential mechanisms for encephalopathy, the complicated issue of choosing which morbidity to take on and how the maternal level of care may influence outcomes. The reader should be able to better understand the limitations of current testing and the profound levels of maternal intervention that have been undertaken to prevent or mitigate the rare, but devastating occurrence of NE. Further, we suggest candidate future approaches to prevent the occurrence, and decrease the severity of NE. Any future improvements in the NE syndrome cannot be achieved via obstetric intervention and management alone or conversely, by improvements in treatments offered post-birth. Multidisciplinary approaches that encompass prepregnancy health, pregnancy care, intrapartum management and postpartum care will be necessary., Competing Interests: Declaration of competing interest The author has no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Piperine (PIP), a pungent alkaloid found in black pepper, has various pharmacological effects by activating the transient receptor potential vanilloid 1 (TRPV1) receptor. In this study, the regulating effect of PIP on glucose metabolism and the underlying mechanism were examined using an insulin-resistant cell model. Results showed that PIP alleviated glucosamine (GlcN)-induced glucose metabolism disorder (from 59.19 ± 1.90 to 88.36 ± 6.57%), restored cellular redox balance (from 148.43 ± 3.52 to 110.47 ± 3.52%), improved mitochondrial function (from 63.76 ± 4.87 to 85.98 ± 5.12%), and mitigated circadian disruption in HepG2 cells via the mediation of circadian clock gene Bmal1 . After the knockdown of the Trpv1 gene, the modulating effect of PIP on Bmal1 -mediated glucose metabolism was weakened, indicating that PIP alleviated Bmal1 -involved insulin resistance and circadian misalignment in a Trpv1 -dependent manner in HepG2 cells.

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., Competing Interests: Conflict of Interest: No conflict of interest is declared by the authors., (©Copyright 2023 by the Turkish-German Gynecological Education and Research Foundation. Journal of the Turkish-German Gynecological Association is published by Galenos Publishing House.)

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., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Human immunodeficiency virus (HIV) resulted in considerable morbidity and mortality. Following antiretroviral therapy (ART), the life expectancy of HIV-infected patients increased; however, they were more at risk of developing chronic diseases such as endocrinopathies. This study aimed to determine the prevalence of dysglycemia, dyslipidemia, and metabolic syndrome among patients with HIV infection., Methods: This cross-sectional study was conducted on HIV-infected patients referring to Loghman Hakim Hospital (Tehran, Iran) between April 2020 and April 2021. We examined demographic features, medical history, and laboratory tests indicating the metabolic status of the patients. Eventually, collected data were processed using SPSS version 23., Results: The mean age of 68 confirmed HIV patients was 39.85±10.54 years and 64.7% were male. BMI (MD = 2.57, 95% CI = [0.25, 4.88], P = 0.035), cholesterol (MD = 22.73, 95% CI = [4.70, 40.76], P = 0.014), HDL (MD = 8.54, 95% CI = [2.06, 15.02], P = 0.011), and LDL of women was significantly higher than men (MD = 22.43, 95% CI = [7.60, 37.27], P = 0.004). Additionally, 30 patients (44.1%) suffered from metabolic syndrome. The prevalence of metabolic syndrome differed significantly between men (34.1%) and women (62.50%) ( P = 0.024)., Conclusion: Dysglycemia, dyslipidemia, and metabolic syndrome are common among HIV-infected patients. Thus, periodic evaluation of the patients can be advantageous in early diagnosis and timely treatment., Competing Interests: The authors declare that they have no competing interests., (© 2023 Iran University of Medical Sciences.)

Haloxyfop-P-methyl is used extensively in agricultural production, and its metabolites in soil have potentially toxic effects on aquatic ecosystems. In this study, we explored the toxicity of haloxyfop-P-methyl on Chiromantes dehaani. The results of the 21-day toxicity test showed that haloxyfop-P-methyl decreased the weight gain (WG), specific growth rate (SGR) and hepatosomatic index (HSI). In glucose metabolism, haloxyfop-P-methyl reduced pyruvate, lactate, lactate dehydrogenase and succinate dehydrogenase, but enhanced glucose-6-phosphate dehydrogenase and hexokinase. Furthermore, expression of glucose metabolism-related genes was upregulated. We cloned the full-length CdG6PDH gene, which contains a 1587 bp ORF that encoded a 528 amino acid polypeptide. In antioxidant system, haloxyfop-P-methyl increased glutathione, thioredoxin reductase and thioredoxin peroxidase activities and activated the Nrf2/ARE pathway through upregulation of ERK, JNK, PKC and Nrf2. In immunity, low concentrations haloxyfop-P-methyl, or short-term exposure, upregulated the expression of immune-related genes and enhanced immune-related enzymes activity, while high concentrations or long-term exposure inhibited immune function. In summary, haloxyfop-P-methyl inhibited the growth performance, disrupted glucose metabolism, activated the antioxidant system, and led to immunotoxicity. The results deepen our understanding of the toxicity mechanism of haloxyfop-P-methyl and provide basic biological data for the comprehensive assessment of the risk of haloxyfop-P-methyl to the environment and humans., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lipid and glucose metabolism are critical for human activities, and their disorders can cause diabetes and obesity, two prevalent metabolic diseases. Studies suggest that the bone involved in lipid and glucose metabolism is emerging as an endocrine organ that regulates systemic metabolism through bone-derived molecules. Sclerostin, a protein mainly produced by osteocytes, has been therapeutically targeted by antibodies for treating osteoporosis owing to its ability to inhibit bone formation. Moreover, recent evidence indicates that sclerostin plays a role in lipid and glucose metabolism disorders. Although the effects of sclerostin on bone have been extensively examined and reviewed, its effects on systemic metabolism have not yet been well summarized. In this paper, we provide a systemic review of the effects of sclerostin on lipid and glucose metabolism based on in vitro and in vivo evidence, summarize the research progress on sclerostin, and prospect its potential manipulation for obesity and diabetes treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Diabetes is a chronic disease caused by impaired glucose metabolism. This study aimed to design and evaluate the effect of a lifestyle promotion program based on the PRECEDE-PROCEED model among pre-diabetic individuals., Methods: This randomized controlled trial evaluated the effect of a lifestyle promotion program using the PRECEDE-PROCEED model among pre-diabetic individuals in Hoveizeh city in 2019. The study collected information on the disease status and risk factors associated with non-communicable conditions from the website of Hoveizeh Cohort Study Center. The primary outcome of the study was the percentage of glycated hemoglobin (HbA1c) with a three-month follow-up., Results: A total of 240 individuals participated in the study. There was no significant difference in anthropometric characteristics between the intervention and control groups (P < 0.05). Initially, there was no significant difference in the mean HbA1c between the intervention and control groups (P = 0.97). However, after three months of intervention, a statistically significant difference was observed (P > 0.001). The results indicated an increase in the mean quality of life in the intervention group, but no significant difference was found between the two groups or before and after the intervention within each group (P < 0.05)., Conclusion: The findings suggest that the PRECEDE-PROCEED model provides a suitable framework for training pre-diabetic individuals and patients with type 2 diabetes mellitus (T2DM) to promote self-care behaviors., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01273-7., Competing Interests: Competing InterestsThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

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., Competing Interests: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (© 2023 The Author(s).)

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., (© 2023. The Author(s).)

Introduction: Physical exercise can improve glucose metabolism; however, the best type, volume, intensity, and frequency aren't knowledge. High-Intensity Interval Training (HIIT), an emergent exercise type implicated as a short time-efficient exercise to improve metabolic health, needs more investigation regarding the traditional Moderate-Intensity Continuous Training (MICT)., Objective: To identify the effects of MICT and HIIT on glycemic control of older people with glucose metabolism impairments., Methods: Our research question was based on the PICO model and the systematic review of the literature according to the guidelines of the preferred report items for systematic reviews and PRISMA meta-analyses. An extensive search was conducted in the Web of Science, PubMed, and Scielo databases. Only English language papers were included. The keywords used were "HIIT and metabolism of the elderly", "HIIT and glucose metabolism of the elderly", and "MICT and metabolism of the elderly", which were crossed with the Boolean operators "AND" and "OR" or both according to the guidelines of the PRISMA., Results: Seventy papers were retrieved in the initial search. After applying all inclusions and exclusion parameters, 63 articles were excluded. In the end, six papers were classified as eligible for this study. All data categorically demonstrates that both HIIT and MICT can improve glucose metabolism with a larger effect size towards the HIIT model after the meta-analysis, pointing to HIIT as the most effective strategy., Conclusion: Both modalities can improve glucose metabolism in the elderly with a clear advantage for HIIT over MICT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: To investigate the relation of established glucose and lipid metabolism indexes and blood inflammatory biomarkers with severe periodontitis in systemically healthy patients., Methods: Systemically healthy Stage III/IV periodontitis patients (case group) (n = 397), Stage II periodontitis patients (n = 36), and periodontally healthy subjects (control group) (n = 285) were recruited. A periodontal examination, complete blood cell examination, and blood biochemical examination were conducted for all participants. Full-mouth apical films were taken for the case group. Both the case and control groups were divided by age into younger (≤ 35 years) and elder subjects. Multiple logistic regression analysis and Pearson correlation analysis were conducted. A logistic least absolute shrinkage and selection operator (LASSO) model was constructed for the younger subgroups., Results: Various glucose and lipid metabolism indexes and blood inflammatory biomarkers significantly differed between severe periodontitis patients and healthy controls, and the younger subgroups presented a greater degree of statistical differences than the elder ones. More pairs of periodontal parameters and blood indexes with significantly fair linear correlations were found in the younger patient subgroup. A logistic LASSO regression model containing eight blood indexes to assess a severe periodontitis outcome in younger subgroups showed satisfactory predictive ability., Conclusion: The present study revealed various glucose and lipid metabolism indexes and blood inflammatory biomarkers significantly differ between severe periodontitis patients and healthy controls, especially in the younger subgroups. A LASSO regression model could be a viable option to assess severe periodontitis risk for younger patients., (© 2022 American Academy of Periodontology.)

To explore the independent and combined effects of ESRα methylation and progesterone on impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), a case-control study including 901 subjects was conducted. Generalized linear models were performed to assess the independent and combined effects of ESRα methylation and progesterone on IFG or T2DM. Methylation level of cytosine-phosphoguanine (CpG) 1 in the estrogen receptor α ( ESRα ) gene was positively related to IFG in both men (odds ratio ( OR ) (95% confidence interval ( CI )): 1.77 (1.05, 3.00)) and postmenopausal women ( OR (95% CI ): 1.82 (1.09, 3.04)), whereas the association between CpG 1 and T2DM was not significant. Positive associations of progesterone with IFG and T2DM were observed in both men ( OR (95% CI ): 2.03 (1.18, 3.49) and 3.00 (1.63, 5.52)) and postmenopausal women ( OR (95% CI ): 2.13 (1.27, 3.56) and 3.30 (1.85, 5.90)). Participants with high CpG 1 methylation plus high progesterone had an increased risk of IFG and T2DM, both in men and postmenopausal women. ESRα methylation and progesterone were positively associated with IFG, and the positive association between progesterone and T2DM was also found. Importantly, we firstly found the combined effects of ESRα methylation and progesterone on IFG and T2DM.

Objective: To explore the mechanism of electroacupuncture (EA) at "Zusanli" (ST36) on improving glucose metabolism disorder in chronic restraint induced depressed rats., Methods: A total of 30 male SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The depression model was established by chronic restraint 2.5 h each day for 4 weeks. For rats in the EA group, EA stimulation (1 mA, 2 Hz, 30 min) was applied to bilateral ST36 during the modeling period, once a day for 4 weeks. The body weight of the rats was recorded before and after modeling. The behavior of rats was observed by sugar-water preference and forced swimming after modeling. The contents of glucose and glycosylated albumin in serum were determined by biochemical method. The histopathological morphology and liver glycogen content were observed by HE and PAS staining. The expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-PI3K (p-PI3K), protein kinase B (Akt), p-Akt, glycogen synthase kinase-3β (GSK3β) and p-GSK3β proteins in liver were determined by Western blot., Results: Compared with the control group, the weight increment and sugar-water preference index decreased ( P <0.01), the immobile swimming time was prolonged ( P <0.01), the glucose and glycosylated albumin contents in serum increased ( P <0.05), the expression of p-Akt protein and the ratio of p-Akt/Akt in liver tissues decreased ( P <0.001), the expression of p-GSK3β protein and the ratio of p-GSK3β/GSK3β in liver tissues increased ( P <0.01, P <0.001) in the model group. Compared with the model group, the weight increment and sugar-water preference index increased ( P <0.05), the immobile swimming time was shortened ( P <0.05), the glucose and glycosylated albumin contents in serum decreased ( P <0.05), the expressions of p-PI3K and p-Akt proteins and the ratio of p-PI3K/PI3K and p-Akt/Akt in liver tissues increased ( P <0.05), the expression of p-GSK3β protein and the ratio of p-GSK3β/GSK3β in liver tissues decreased ( P <0.01) in the EA group. HE staining showed that the structure of the hepatic lobule was intact, no obvious inflammatory cell infiltration or fibrosis was observed in the lobule and interstitium, and no abnormalities were observed in the small bile duct, portal vein and artery in the portal area. PAS staining showed that the intensity of staining from the center of the hepatic lobule to the periphery of the hepatic lobule was gradually enhanced in the blank group, that is, the glycogen-rich granules in the hepatic cells were gradually increased; most of the hepatocytes were light colored and glycogen was lost significantly in the model group; while the intensity of hepatocyte staining increased, the staining intensity of the perilobular zone was weaker than that in the blank group, and the glycogen particles partially recovered in the EA group., Conclusion: EA intervention can regulate glucose metabolism disorder in chronic restraint induced depressed rats through PI3K/Akt/GSK3β signaling pathway.

Glucose metabolism disorder triggered by a high-energy diet is associated with circadian disruption in the brain, peripheral tissues and gut microbiota. The present study aims to investigate the regulating effects of capsaicin (CAP) on the diet-induced disturbances of glucose homeostasis and gut microbiota in respect of circadian rhythm-related mechanisms. Our results indicated that CAP significantly ameliorated glucose metabolism disorder in mice induced by a high-fat and high-fructose diet (HFFD). The rhythmic expressions of circadian clock genes ( Bmal1 , Clock , and others) and glucose metabolism-related genes ( Pgc-1α , Glut2 , G6pc , and Pepck ) in the liver disrupted by an abnormal diet were also recovered by CAP. Microbial studies using 16S rDNA sequencing revealed that CAP modulated the structure and composition of gut microbiota and improved the circadian oscillations of Firmicutes and Bacteroidetes at the phylum level and Allobaculum , Bacteroides , Bifidobacterium , and Alistipes at the genus level. Correlation analysis indicated that a close correlation existed between intestinal microbiota, hepatic circadian gene expressions and the level of glucose metabolism-related factors, indicating that CAP could alleviate HFFD-induced disturbances of glucose metabolism and gut microbiota associated with circadian clock related mechanisms.

Perceived discrimination is a significant risk factor for worse ageing health outcomes. Yet, the specific individual and relational stress pathways linking discrimination to disease are less understood, especially in the context of cardiometabolic health. We tested family stress and psychophysiological distress (negative affect and high-risk lipid/fat metabolism) as mediators linking perceived discrimination to cardiometabolic morbidity and health appraisal over 20 years for midlife adults. Using data from participants who completed the Biomarker Project (2004-2009) of the Midlife in the U.S. project, and examining data over the study's three waves (1995-1996, 2004-2006, and 2013-2014), we used structural equation modelling to test pathways for participants who reported zero cardiometabolic conditions at baseline (n = 799). Greater Time 1 discrimination was associated with greater Time 2 family strain, which was in turn associated with worse negative affect; worse Time 2 negative affect was associated with worse Time 3 health appraisal; metabolic lipids risk did not serve as an indirect pathway to Time 3 cardiometabolic morbidity (χ 2  = 147.74, p < 0.001; RMSEA = 0.056; CFI = 0.902; SRMR = 0.047). The inclusion of family in interventions to mitigate the impact of discrimination may be indicated for promoting cardiometabolic wellness., (© 2022 John Wiley & Sons Ltd.)

Previous studies have shown that low birth weight (LBW) individuals are at higher risk of glucose metabolism disorders compared with normal birth weight (NBW) individuals under overnutrition conditions, but the mechanism remains unclear. To explore the underlying mechanism of glucose metabolism disorders induced by LBW under overnutrition in adulthood, the prenatal malnutrition method was applied to ICR mice to establish the LBW mice model and high-fat diets were used to mimic overnutrition conditions. Then the mechanism was further explored on Hepg2 cells treated with nutritional deprivation plus palmitic acid. The results showed that LBW plus high-fat interventions will cause glucose metabolism disorders and inhibit autophagy flux in adulthood. Moreover, the expression of TRPC5-regulated AMPK/mTOR autophagy pathway was downregulated by LBW with high-fat interventions. Collectively, LBW plus high-fat intervention increased the risk of glucose metabolism disorders, which may be related to the alteration of TRPC5 expression level and its regulation of the AMPKα/mTOR autophagy pathway. This study may provide a fundamental basis for the molecular mechanism of glucose metabolism disorders induced by LBW with high-fat diets in adulthood and a new target for the treatment of metabolic diseases in LBW individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to fine particulate matter (PM 2.5 ) was associated with an increased incidence of liver metabolic disease. Melatonin has been shown to prevent liver glucolipid metabolism disorders. However, whether melatonin could rescue PM 2.5 -induced liver metabolic abnormalities remains uncertain. This study was to evaluate the mitigating effect of melatonin on PM 2.5 -accelerated hepatic glucose metabolism imbalance in vivo and in vitro. Schiff periodic acid shiff staining and other results showed that PM 2.5 led to a decrease in hepatic glycogen reserve and an increase in glucose content, which was effectively alleviated by melatonin. Targeted lipidomics is used to identify lipid biomarkers associated with this process, including glycerolipids, glycerophospholipids, and sphingolipids. In addition, gene microarray and quantitative polymerase chain reaction analysis of ApoE -/- mice liver suggested that PM 2.5 activated the miR-200a-3p and inhibited DNAJB9, and the targeting relationship was verified by luciferase reports for the first time. Further investigation demonstrated that DNAJB9 might motivate endoplasmic reticulum (ER) stress by regulating Ca 2+ homeostasis, thus altering the protein expression of GSK3B, FOXO1, and PCK2. Meanwhile, melatonin effectively inhibited miR-200a-3p and glucose metabolism disorder. Knockout of miR-200a-3p in L02 cells revealed that miR-200a-3p is indispensable in the damage of PM 2.5 and the therapeutic effect of melatonin. In summary, melatonin alleviated PM 2.5 -induced liver metabolic dysregulation by regulating ER stress via miR-200a-3p/DNAJB9 signaling pathway. Our data provide a prospective targeted therapy for air pollution-related liver metabolism disorders., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Periodontitis has been demonstrated to be bidirectionally associated with diabetes and has been recognized as a complication of diabetes. As a periodontal pathogen, Porphyromonas gingivalis is a possible pathogen linking periodontal disease and systemic diseases. It has also been found to be involved in the occurrence and development of diabetes. In this study, 6-week-old male C57BL/6 mice were orally administered the P. gingivalis strain ATCC381 for 22 weeks. Histological analysis of the gingival tissue and quantified analysis of alveolar bone loss were performed to evaluate periodontal destruction. Body weight, fasting glucose, glucose tolerance test (GTT), and insulin tolerance test (ITT) were used to evaluate glucose metabolism disorder. We then analyzed the expression profiles of inflammatory cytokines and chemokines in gingival tissue, the liver, and adipose tissue, as well as in serum. The results showed that mice in the P. gingivalis -administered group developed apparent gingival inflammation and more alveolar bone loss compared to the control group. After 22 weeks of P. gingivalis infection, significant differences were observed at 30 and 60 min for the GTT and at 15 min for the ITT. P. gingivalis -administered mice showed an increase in the mRNA expression levels of the pro-inflammatory cytokines (TNF-α, IL-6, IL-17, and IL-23) and chemokines (CCL2, CCL8, and CXCL10) in the gingiva and serum. The expression levels of the glucose metabolism-related genes were also changed in the liver and adipose tissue. Our results indicate that oral administration of P. gingivalis can induce changes in the inflammatory cytokines and chemokines in the gingiva and blood, can lead to alveolar bone loss and to inflammatory changes in the liver and adipose tissues, and can promote glucose metabolism disorder in mice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kang, Zhang, Xue, Duan, Chen, Cai and Luan.)

Vitamin D deficiency is associated with an increase in the occurrence of cardiometabolic events, but the evidence of this relationship in adolescence is still limited. Thus, we analyzed the association between vitamin D deficiency and cardiometabolic risk factors in adolescents. Observational studies were searching in PubMed/Medline, Embase, Scopus, Web of Science, Science Direct, Lilacs, and Google Scholar database. Random effects models were used to summarize standardized mean differences for as a summary measure. The certainty of the evidence was verified using the Cochrane recommendations. A total of 7537 studies were identified, of which 32 were included in the systematic review and 24 in the meta-analysis.Vitamin D deficiency was associated with increased systolic pressure (SMD = 0.22; 95%CI = 0.10; 0.34), diastolic pressure (SMD = 0.23; 95%CI = 0.10; 0.35), glycemia (SMD = 0.13; 95%CI = 0.05; 0.12), and insulin (SMD = 0.50; 95%CI = 0.15; 0.84), an increase in the HOMA index (SMD = 0.48; 95%CI = 0.36; 0.60), high triglyceride values (SMD = 0.30; 95%CI = 0.11; 0.49), and reduced HDL concentrations (SMD= -0.25; 95%CI = -0.46; -0.04). No statistically significant association was observed for glycated hemoglobin, LDL cholesterol, and total cholesterol. Most of the studies presented low and moderate risks of bias, respectively. The certainty of the evidence was very low for all the outcomes analyzed. Vitamin D deficiency was associated with increased exposure to the factors linked to the occurrence of cardiometabolic diseases in adolescents. Systematic Review Registration: PROSPERO (record number 42,018,086,298)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The type 2 diabetes risk after gestational diabetes mellitus (GDM) is twice as high in South Asian compared to European women. Current guidelines differ regarding which test to use as a screening-tool post-GDM. We aimed to identify ethnic differences in the prevalence rates and early predictors for actionable HbA 1c (defined as prediabetes and diabetes) short time after GDM., Methods: This cross-sectional study, enrolling South Asian and Nordic women 1-3 years after a diagnosis of GDM, was undertaken at three hospitals in Norway. We performed a clinical and laboratory evaluation including an oral glucose tolerance test (OGTT). Medical records were used to retrieve data during pregnancy. Prediabetes was classified with HbA 1c alone or combined with OGTT glucose measurements according to the WHO, WHO-IEC, and ADA criteria (fasting plasma glucose (FPG) 6.1-6.9 mmol/L, FPG 6.1-6.9 mmol/L and/or HbA 1c 42-47 mmol/mol (6.0-6.4%), and FPG 5.6-6.9 mmol/L and/or HbA 1c 39-47 mmol/mol (5.7-6.4%)). Ethnic differences in prevalence and predictors of glucose deterioration were assed by χ 2 (Pearson) tests and logistic regression models., Results: We included 163 South Asian and 108 Nordic women. Actionable HbA 1c levels were highly prevalent and more so among South Asian than Nordic women (WHO-IEC-HbA 1c : 25.8% vs. 6.5% (p ≤ 0.001), ADA-HbA 1c : 58.3% vs. 22.2% (p ≤ 0.001)). Although adding OGTT-data gave higher combined prevalence rates of prediabetes and diabetes (WHO: 65.6% vs. 47.2% (p ≤ 0.05), WHO-IEC: 70.6% vs. 47.2% (p ≤ 0.001), ADA: 87.8% vs. 65.7% (p ≤ 0.001)), the excess risk in the South Asian women was best captured by the HbA 1c . Important predictors for glucose deterioration after GDM were: South Asian ethnicity, GDM before the index pregnancy, use of glucose-lowering drugs in pregnancy, higher age, and higher in-pregnancy fasting glucose levels., Conclusions: In women with GDM 1-3 year previously, we found high prevalence and significant ethnic differences in actionable ADA-HbA 1c levels, with South Asian ethnicity, GDM before the index pregnancy, and the use of glucose-lowering drugs in pregnancy as the most important risk factors. This study reinforces the importance of annual screening-preferably with HbA 1c measurements-to facilitate early intervention after GDM., (© 2022. The Author(s).)

Objective: Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear., Methods: An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5'-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins., Results: XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons., Conclusion: Adiponectin may be a key regulator linking depression and metabolic disorders; regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.)

Prolonged excess of glucocorticoids (GCs) has adverse systemic effects leading to significant morbidities and an increase in mortality. Metabolic alterations associated with the high level of the GCs are key risk factors for the poor outcome. These include GCs causing excess gluconeogenesis via upregulation of key enzymes in the liver, a reduction of insulin sensitivity in skeletal muscle, liver and adipose tissue by inhibiting the insulin receptor signalling pathway, and inhibition of insulin secretion in beta cells leading to dysregulated glucose metabolism. In addition, chronic GC exposure leads to an increase in visceral adipose tissue, as well as an increase in lipolysis resulting in higher circulating free fatty acid levels and in ectopic fat deposition. Remission of hypercortisolism improves these metabolic changes, but very often does not result in full resolution of the abnormalities. Therefore, long-term monitoring of metabolic variables is needed even after the resolution of the excess GC levels., (© 2022 British Society for Neuroendocrinology.)

Acrylamide (AA) is a common food contaminant that causes glucose metabolism disorders (GMD). However, the underlying mechanism remains unclear. Female Sprague Dawley (SD) rats were treated with AA via gavage for 21 days, and the glucose and insulin levels, gut microbiota, intestinal barrier, and metabolism were analyzed. The results revealed that AA elevated serum glucose levels, reduced insulin levels and caused intestinal barrier injury. The 16S amplicon sequencing and non-targeted metabolomics showed that AA induced gut microbiota dysbiosis and bile acids (BAs) metabolism disorder. Specifically, AA decreased the abundance of Lactobacillus and Bacteroides in the cecal contents, and increased the cholic acid (CA) content in feces. Meanwhile, the expression of ileum apical sodium-dependent bile acid transporter (ASBT) responsible for CA reabsorption was suppressed. Further analysis indicated that BAs sensing nuclear receptor farnesoid X receptor (FXR) gene was activated and glucagon-like peptide-1 (GLP-1) which stimulates insulin secretion was downregulated. In addition, activation of FXR increased the expression of fibroblast growth factor 15 (FGF15), which resulted in the inhibition of hepatic BAs synthesis. Overall, this study demonstrated that AA-induced GMD is associated with the gut-microbiota-CA-FXR/GLP-1 axis. These findings add new knowledge to the AA-induced GMD and provide a basis for potential AA toxicity mitigation by manipulation of the gut microbiota., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis., Methods: To determine the effect of an educational intervention delivered by primary care nurses to improve sleep hygiene, a parallel, open-label clinical trial in subjects aged 18 and older with impaired fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) was performed. Study variables were sex, age, fasting glucose, glycated haemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, body mass index, antidiabetic treatment, diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. The intervention aimed to develop skills to improve sleep through nine simple tips. An analysis of covariance was performed on all the mean centred outcome variables controlling for the respective baseline scores., Results: In the intervention group, PSQI dropped, the duration and quality of sleep increased, and a decrease in fasting glucose and in HbA1c levels was observed., Conclusion: The proposed intervention is effective for improving sleep quality, length and efficiency, and for decreasing fasting glucose and HbA1c levels in only 3 months. These findings support the importance of sleep and circadian rhythm education focused on improving IFG and T2DM.

Background: Vascular dysfunction is a biological pathway whereby particulate matter (PM) exerts deleterious cardiovascular effects. The effects of ambient PM on vascular function in prediabetic individuals are unclear., Methods: A panel study recruited 112 Beijing residents with and without prediabetes. Multiple vascular function indices were measured up to 7 times. The associations between vascular function indices and short-term exposure to ambient PM, including fine particulate matter (PM 2.5 ), ultrafine particles, accumulation mode particles, and black carbon, and the modification of these associations by glucose metabolic status were examined using linear mixed-effects models., Results: Increases in brachial artery pulse pressure, central aortic pulse pressure, and ejection duration, and decreases in subendocardial viability ratio and reactive hyperemia index were significantly associated with at least one PM pollutant in all participants, indicating increased vascular dysfunction. For example, for an interquartile range increment in 5-day moving average ultrafine particles, brachial artery pulse pressure, and central aortic pulse pressure increased 5.4% (0.8%-10.4%) and 6.2% (1.2%-11.5%), respectively. Additionally, PM-associated changes in vascular function differed according to glucose metabolic status. Among participants with high fasting blood glucose levels (≥6.1 mmol/L), PM exposure was significantly associated with increased brachial artery systolic blood pressure, central aortic systolic blood pressure, brachial artery pulse pressure, central aortic pulse pressure, and augmentation pressure normalized to a heart rate of 75 bpm and decreased subendocardial viability ratio and reactive hyperemia index. Weaker or null associations were observed in the low-fasting blood glucose group., Conclusions: Glucose metabolic disorders may exacerbate vascular dysfunction associated with short-term ambient PM exposure.

Background: There was considerable debate regarding the effect of mean blood glucose (MBG) and glycemic variability (GV) on the mortality of septic patients. This retrospective cohort study aimed to assess the association between MBG and GV with ICU mortality of sepsis patients and to explore the optimal MBG range., Methods: Sepsis patients were enrolled from the Medical Information Mart for Intensive Care IV database (MIMIC-IV). MBG and glycemic coefficient of variation (Glu CV ) were, respectively, calculated to represent the overall glycemic status and GV during ICU stay. The associations between MBG, Glu CV , and ICU mortality of the septic patients were assessed by using multivariate logistic regression in different subgroups and the severity of sepsis. Restricted cubic splines evaluated the optimal MBG target., Results: A total of 7,104 adult sepsis patients were included. The multivariate logistic regression results showed that increased MBG and Glu CV were significantly correlated with ICU mortality. The adjusted odds ratios were 1.14 (95% CI 1.09-1.20) and 1.05 (95% CI 1.00-1.12). However, there was no association between hyperglycemia and ICU mortality among diabetes, liver disease, immunosuppression, and hypoglycemia patients. And the impact of high Glu CV on ICU mortality was not observed in those with diabetes, immunosuppression, liver disease, and non-septic shock. The ICU mortality risk of severe hyperglycemia (≧200 mg/dl) and high Glu CV (>31.429%), respectively, elevated 2.30, 3.15, 3.06, and 2.37, 2.79, 3.14-folds in mild (SOFA ≦ 3), middle (SOFA 3-7), and severe group (SOFA ≧ 7). The MBG level was associated with the lowest risk of ICU mortality and hypoglycemia between 120 and 140 mg/dl in the subgroup without diabetes. For the diabetic subset, the incidence of hypoglycemia was significantly reduced when the MBG was 140-190 mg/dl, but a glycemic control target effectively reducing ICU mortality was not observed., Conclusion: MBG and Glu CV during the ICU stay were associated with all-cause ICU mortality in sepsis patients; however, their harms are not apparent in some particular subgroups. The impact of hyperglycemia and high GV on death increased with the severity of sepsis. The risk of ICU mortality and hypoglycemia in those with no pre-existing diabetes was lower when maintaining the MBG in the range of 120-140 mg/dl., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Tao, Sun, Zhang, Jiang, Liu, Ling, Zhang, Xiao, Hua, Zhu and Yang.)

Orphan nuclear receptor Nur77 has been reported to be implicated in a diverse range of metabolic processes, including carbohydrate metabolism and lipid metabolism. However, the detailed mechanism of Nur77 in the regulation of metabolic pathway still needs to be further investigated. In this study, we created a global nur77 knockout zebrafish model by CRISPR/Cas9 technique, and then performed whole-organism RNA sequencing analysis in wildtype and nur77 -deficient zebrafish to dissect the genetic changes in metabolic-related pathways. We found that many genes involved in amino acid, lipid, and carbohydrate metabolism changed by more than twofold. Furthermore, we revealed that nur77 -/- mutant displayed increased total cholesterol (TC) and triglyceride (TG), alteration in total amino acids, as well as elevated glucose. We also demonstrated that the elevated glucose was not due to the change of glucose uptake but was likely caused by the disorder of glycolysis/gluconeogenesis and the impaired β-cell function, including downregulated insb expression, reduced β-cell mass, and suppressed insulin secretion. Importantly, we also verified that targeted expression of Nur77 in the β cells is sufficient to rescue the β-cell defects in global nur77 -/- larvae zebrafish. These results provide new information about the global metabolic network that Nur77 signaling regulates, as well as the role of Nur77 in β-cell function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Tian, Kang, Yuan, Liu, Li, Liu and Li.)

Background: We aimed to build mouse models of small for gestational age (SGA), recapitulating failure of catch-up growth and dysregulated metabolic outcomes in adulthood., Methods: Pregnant C57BL/6 mice were given a protein-restricted diet (PRD; 6% kcal from protein) during pregnancy without (model 1) or with cross-fostering (model 2). Model 3 extended the PRD to the end of the lactation period. Model 4 changed to a 9% PRD without cross-fostering., Results: Model 1 yielded a reduced size of offspring with a poor survival rate. Model 2 improved survival but offspring showed early catch-up growth. Model 3 maintained a reduced size of offspring after weaning with a higher body mass index and blood glucose levels in adult stages. Model 4 increased the survival of the offspring while maintaining a reduced size and dysregulated glucose metabolism., Conclusion: Models 3 and 4 are suitable for studying SGA accompanying adulthood short stature and metabolic disorders.

Growth differentiation factor 15 (GDF15) is a stress-response cytokine which belongs to the transforming growth factor β superfamily. Although GDF15 was initially found to have a role in metabolic diseases, the association between GDF15 and dysglycemic status remains inconclusive. Thus, the aim of this study was to examine the relationships between GDF15 and different glycemic statuses in non-obese subjects. We enrolled 502 non-obese subjects, among individuals who had normal glucose tolerance (NGT; n=125), isolated impaired fasting glucose (IFG; n=116), isolated impaired glucose tolerance (IGT; n=106), IFG plus IGT (n=27), and newly diagnosed diabetes (NDD; n=128). A multivariate linear regression analysis of GDF15 levels was used to find independent predictors. The median (IQR) GDF15 levels were 1641.0 (1187.0-1985.5) pg/mL, 1656.1 (1226.8-2379.7) pg/mL, 1487.8 (1145.9-1987.2) pg/mL, 1722.2 (1172.9-1939.0) pg/mL, and 2204.5 (1767.4-2919.1) pg/mL in NGT, IFG, IGT, IFG plus IGT, and NDD groups, respectively. The NDD group had significantly higher GDF15 levels than those with NGT, IFG, IGT, and IFG plus IGT. The IFG group had a significantly higher GDF15 value than the NGT group. In multivariate linear regression analysis, IFG (beta=0.145, 95% CI 192.487 to 740.937, p=0.001), NDD (beta=0.227, 95% CI 390.459 to 888.145, p<0.001), and high-sensitivity C reactive protein (beta=0.105, 95% CI 3.276 to 27.768, p=0.013) were independently associated with GDF15 levels. Non-obese subjects with isolated IFG and NDD had significantly higher GDF15 levels than those with NGT. In addition, A1C was independently associated with GDF15 levels. IFG and NDD, but not isolated IGT or IFG plus IGT, were positively associated with GDF15 levels., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Maternal lipopolysaccharide (LPS) exposure during pregnancy induces metabolic abnormalities in male offspring, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of maternal LPS exposure during pregnancy on metabolic profiling of maternal serum and male fetal liver using Liquid Chromatograph Mass Spectrometer techniques. From day 15 to day 17 of gestation, pregnant mice were administered intraperitoneal LPS (experimental group) (50 μg/kg/d) or saline (control group). On day 18 of gestation, maternal serum and male fetal liver were collected. After LPS exposure, levels of 38 and 75 metabolites, mainly glycerophospholipid and fatty acid metabolites, were altered in maternal serum and male fetal liver, respectively. It was found that in maternal serum and male fetal livers, the glycerophospholipids containing saturated fatty acids (SFAs) and the SFAs were upregulated, while the glycerophospholipids containing polyunsaturated fatty acids (PUFAs) and the PUFAs were downregulated. This concordance between maternal and fetal alterations in glycerophospholipid and fatty acid metabolites may be a metabolomic signature of the early intrauterine period and may provide insight into the mechanisms by which maternal LPS exposure induces disorders of glucose metabolism in male offspring., (© 2021 John Wiley & Sons, Ltd.)

Vehicle exhaust, as one of the most important compositions of air pollution, induced various adverse health effects, especially diabetes, on human beings. Even though monitoring and epidemiological data indicates that particle-bound polycyclic aromatic hydrocarbons (PAHs) is an inducing factor of diabetes, the specific causative mechanisms are still unclear. In the current study, the concentration of particulate matters (PMs, including PM 1.0 , PM 2.5 and PM 10.0 ) and PAHs was investigated at rush hour of weekday in three urban underground parking garages (UPGs). To evaluate the impacts of particle-bound PAHs on human beings, analysis of non-target metabolomics and unmetabolized PAHs were conducted for UPG and non-UPG worker urine samples. The results showed that the highest concentrations of PMs and total PAHs were found at the UPG entrance. The concentrations of unmetabolized 5-6 rings PAHs in the UPG worker urine were significantly higher than that in non-UPG worker urine samples, which induced glucose metabolism disorders through hypoxia-inducible factor 1 (HIF-1) signaling pathway. This could be a reason for particle-bound PAHs induced-diabetes on road workers, drivers and garage staff. These findings can serve as a step towards air pollution management and the pathological mechanism analysis of environmental factor induced-diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study aimed to assess the effects of non-surgical periodontal treatment (NSPT) of chronic periodontitis on insulin sensitivity, glucose tolerance, and serum C reactive protein (CRP) level in individuals without diabetes. Twenty individuals without diabetes with chronic periodontitis underwent NSPT, which consisted of complete scaling, polishing, root planing, and irrigation of the periodontal pockets with a 10% povidone-iodine solution. Periodontal indices (plaque index, gingival bleeding index, pocket depth, and clinical attachment loss), insulin sensitivity using the Short Insulin Tolerance Test index (KITT), glucose tolerance derived from oral glucose tolerance test, and serum CRP level were measured before and 3 months after the intervention. This study was carried out at the National Obesity Center of Yaoundé Central Hospital, Cameroon. After 3 months, we observed significant improvement in periodontal parameters (all p<0.001) and insulin sensitivity (3.72 (2.99-4.17) %/min before treatment vs 4.04 (3.67-4.78) %/min after treatment, p=0.001) and significant decrease in serum CRP level (2.35 (1.46-4.18) mg/L before vs 1.53 (1.03-2.12) mg/L after, p=0.033). There was a trend toward improvement in glucose tolerance, although not statistically significant after the intervention. This study suggests that NSPT of chronic periodontitis in individuals without diabetes is associated with increased insulin sensitivity and decreased serum CRP levels.Trial registration number NCT02830113., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2021. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Astrocytes are crucial for the maintenance of brain homeostasis by actively participating in the metabolism of glucose, which is the main energy substrate for the central nervous system (CNS), in addition to other supportive functions. More specifically, astrocytes support neurons through the metabolic coupling of synaptic activity and glucose utilization. As such, diabetes mellitus (DM) and consequent glucose metabolism disorders induce astrocyte damage, affecting CNS functionality. Glioprotective molecules can promote protection by improving glial functions and avoiding toxicity in different pathological conditions, including DM. Therefore, this review discusses specific pathomechanisms associated with DM/glucose metabolism disorder-induced gliotoxicity, namely astrocyte metabolism, redox homeostasis/mitochondrial activity, inflammation, and glial signaling pathways. Studies investigating natural products as potential glioprotective strategies against these deleterious effects of DM/glucose metabolism disorders are also reviewed herein. These products include carotenoids, catechins, isoflavones, lipoic acid, polysaccharides, resveratrol, and sulforaphane., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Inflammation in insulin-sensitive tissues (e.g., liver, visceral adipose tissue [VAT]) plays a major role in obesity and insulin resistance. Recruitment of innate immune cells drives the dysregulation of glucose and lipid metabolism. We aimed to seek the role of Toll like receptor 3 (TLR3), a pattern recognition receptor involved in innate immunity, obesity and the metabolic disorder. TLR3 expression in liver and VAT from diet induced obese mice and in VAT from overweight women was examined. Body weight, glucose homeostasis and insulin sensitivity were evaluated in TLR3 wild-type and knockout (KO) mice on a chow diet (CD) or high-fat diet for 15 weeks. At euthanasia, blood was collected, and plasma biochemical parameters and adipokines were determined with commercial kits. Flow cytometry was used to measure macrophage infiltration and activation in VAT. Standard western blot, immunohistochemistry and quantative PCR were used to assess molecules in pathways about lipid and glucose metabolism, insulin and inflammation in tissues of liver and VAT. Utilizing human and animal samples, we found that expression of TLR3 was upregulated in the liver and VAT in obese mice as well as VAT in overweight women. TLR3-deficiency protected against high-fat diet induced obesity, glucose intolerance, insulin resistance and lipid accumulation. Lipolysis was enhanced in VAT and hepatic lipogenesis was inhibited in TLR3 KO animals. Macrophages infiltration into adipose tissue was attenuated in TLR3 KO mice, accompanied with inhibition of NF-κB-dependent AMPK/Akt signaling pathway. These findings demonstrated that TLR3 ablation prevented obesity and metabolic disorders, thereby providing new mechanistic links between inflammation and obesity and associated metabolic abnormalities in lipid/glucose metabolism., (Copyright © 2021. Published by Elsevier Inc.)

Brain atrophy is related to vascular risk factors and can increase cognitive dysfunction risk. This community-based, cross-sectional study investigated whether glucose metabolic disorders due to body fatness are linked to regional changes in brain structure and a decline in neuropsychological function in cognitively healthy older adults. From 2016 to 2019, 429 participants underwent measurements for cortical thickness and subcortical volume using 3 T magnetic resonance imaging and for cognitive function using the neuropsychological screening battery. The effects of body fatness mediated by impaired glucose metabolism on neuroimaging markers and cognitive function was investigated using partial least square structural equation modeling. Total grey matter volume (β = -0.020; bias-corrected (BC) 95% confidence interval (CI) = -0.047 to -0.006), frontal (β = -0.029; BC 95% CI = -0.063 to -0.005) and temporal (β = -0.022; BC 95% CI = -0.051 to -0.004) lobe cortical thickness, and hippocampal volume (β = -0.029; BC 95% CI = -0.058 to -0.008) were indirectly related to body fatness. Further, frontal/temporal lobe thinning was associated with recognition memory (β = -0.005; BC 95% CI = -0.012 to -0.001/β = -0.005; BC 95% CI = -0.013 to -0.001) and delayed recall for visual information (β = -0.005; BC 95% CI = -0.013 to -0.001/β = -0.005; BC 95% CI = -0.013 to -0.001). Additionally, the smaller the hippocampal volume, the lower the score in recognition memory (β = -0.005; BC 95% CI = -0.012 to -0.001), delayed recall for visual information (β = -0.005; BC 95% CI = -0.012 to -0.001), and verbal learning (β = -0.008; BC 95% CI = -0.017 to -0.002). Our findings indicate that impaired glucose metabolism caused by excess body fatness affects memory decline as well as regional grey matter atrophy in elderly individuals with no neurological disease., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

In the last few decades, obesity has increased dramatically in pediatric patients. Obesity is a chronic disease correlated with systemic inflammation, characterized by the presence of CD4 and CD8 T cell infiltration and modified immune response, which contributes to the development of obesity related diseases and metabolic disorders, including impaired glucose metabolism. In particular, Treg and Th17 cells are dynamically balanced under healthy conditions, but imbalance occurs in inflammatory and pathological states, such as obesity. Some studies demonstrated that peripheral Treg and Th17 cells exhibit increased imbalance with worsening of glucose metabolic dysfunction, already in children with obesity. In this review, we considered the role of adipose tissue immunomodulation and the potential role played by Treg/T17 imbalance on the impaired glucose metabolism in pediatric obesity. In the patient care, immune monitoring could play an important role to define preventive strategies of pediatric metabolic disease treatments.