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Objective: To Investigate the Effects of Qingre Lishi Huatan Recipe on TCM Syndrome Scores, Blood Glucose Metabolism and Serum Levels of monocyte chemoattractant protein -1 (MCP-1), Interleukin-1β (IL-1β) and high mobility group protein B1 (HMGB1) in patients with type 2 diabetes mellitus with phlegm-damp-stasis-heat type. Methods: A total of 104 patients with type 2 diabetes who received treatment from May 2018 to May 2021 in the Enshi Tujia and Miao Autonomous Prefecture Central Hospital were collected as the research objects, and according to the coin tossing method, they were randomly divided into observation group and control group, with 52 cases in each group. The control group was given intensive insulin treatment, while the observation group was given the addition of Qingre Lishi Huatan Recipe on the basis of the control group. The clinical efficacy, TCM symptom scores, blood glucose metabolism, serum MCP-1, IL-1β, HMGB1 indexes and the occurrence of adverse reactions between the comparison groups were evaluated. Results: The total effective rate of the observation group was 90.38% (47/52), which was higher than that 73.08% (38/52) of the control group, and the difference was statistically significant (P<0.05). After treatment, the scores of TCM symptom scores in both groups were decreased, and the TCM symptom scores in the observation group, including including bitter mouth and dry throat, mental fatigue, irritability, red tongue and yellow fur were lower than those in the control group, and the difference was statistically significant (P<0.05). After treatment, the levels of various blood glucose metabolism indexes in the two groups were decreased, and the blood glucose indexes glycosylated hemoglobin (HbA1c), fasting insulin (FINS), and insulin resistance index (HOMA-IR) levels of the observation group were lower than those of the control group, and the differences were higher than those of the control group,and the difference was statistically significant (P<0.05). After treatment, the levels of various inflammatory factors in the two groups were decreased, and the levels of MCP-1, IL-1β, and HMGB1 in the observation group were lower than those in the control group, and the difference was statistically significant (P<0.05). During the treatment period, the incidence of adverse reactions in the observation group and the control group were 15.38% (8/52) and 9.62% (5/52), respectively, and there was no significant difference between the groups (P>0.05). Conclusion: Qingre Lishi Huatan recipe has a good therapeutic effect on type 2 diabetes mellitus with phlegm-damp-stasis-heat type. It can correct the disorder of glucose metabolism, reduce the degree of adverse TCM symptoms, and inhibit the expression of MCP-1, IL-1β, HMGB1 and the incidence of adverse reactions were low. [ABSTRACT FROM AUTHOR]

Background: Islet or β-cell transplantation is a therapeutical approach to substitute the insulin-producing cells which are abolished in type 1 diabetes mellitus. The shortage of human islets as well as the complicated and costly isolation process limit the application of these techniques in daily clinical practice. EndoC-βH is a human β-cell line that readily forms aggregates termed pseudoislets, providing an alternative to primary human islets or β-cells., Methods: EndoC-βH3 cells were seeded and incubated to form pseudoislets. Their insulin secretion was analyzed by ELISA and compared with cell monolayers. Pseudoislets were transplanted into streptozotocin-treated NMRi nu/nu mice. Blood glucose was monitored before and after transplantation and compared with wild types. Grafts were analyzed by immunohistology., Results: This study shows that EndoC-βH cells are able to form pseudoislets by aggregation, leading to an enhanced glucose stimulated insulin secretion in vitro. These pseudoislets were then successfully transplanted into the livers of diabetic mice and produced insulin in vitro. Blood glucose levels of the streptozocin-treated recipient mice were significantly decreased when compared to pre-transplantation and matched the levels found in control mice., Conclusion: We suggest pseudoislets aggregated from EndoC-βH cells as a valuable and promising model for islet transplantation research.

Background: Studies have shown an association between the triglyceride-glucose (TyG) index and carotid artery plaque (CAP). However, the relationship between the TyG index and plaque burden in individuals with primary hypertension remains uncertain. Our study specifically aimed to explore this relationship among primary hypertension patients., Methods: This study involved 5,153 hospitalized patients diagnosed with primary hypertension who were undergoing treatment at the Affiliated Hospital of Jiangxi University of Chinese Medicine. We utilized multivariate logistic regression, penalized spline regression, and generalized additive models to assess the association between the TyG index and CAP burden., Results: There were 2,400 patients with primary hypertension in all. The multivariate study, which took into account all covariables, showed a positive correlation between the TyG index and CAP (OR: 1.25, 95% CI: 1.04-1.5). When the TyG index was evaluated as quartiles, the risk of CAP in the Q3 and Q4 levels of the TyG index were 1.4 (95% CI: 1.03-1.91) and 1.54 (95% CI: 1.11-2.14) times greater than in the Q1 level after adjusting for all covariables ( P for trend < .05). Regardless of whether the TyG index was used as a continuous variable or a categorical variable, it has no significant association with the risk of single plaque after adjusting for all confounders ( p  ≥ .05). The TyG index was found to be substantially correlated with the presence of multiple plaques when analyzed as a continuous variable (OR: 1.32, 95% CI: 1.09-1.59, p  = .004). When the TyG index was evaluated as quartiles, the adjusted OR in Q3 and Q4 were 1.49 (95% CI: 1.06-2.1) and 1.67 (95% CI: 1.16-2.41), respectively, with Q1 as reference ( P for trend = .005). The relationship between the TyG index and the presence of multiple plaques is also consistent in all subgroups., Conclusion: The TyG index is positively associated with the presence of multiple plaques in patients with primary hypertension, whereas no association is found between the TyG index and the presence of a single carotid plaque.

Purpose: To overview the recent literature regarding the relationship between COVID-19 vaccines and glycemic control., Methods: Data were extracted from text and tables of all available articles published up to September 2023 in PubMed Database describing glucose homeostasis data in subjects exposed to COVID-19 vaccines, focusing on patients with diabetes mellitus (DM)., Results: It is debated if the immune system impairment observed in diabetic patients makes them susceptible to lower efficacy of vaccines, but evidence suggests a possible improvement in immune response in those with good glycemic control. Despite their proven protective role lowering infection rates and disease severity, COVID-19 vaccines can result in diabetic ketoacidosis, new-onset diabetes, or episodes of hyper- or hypoglycemia., Conclusions: Evidence with COVID-19 vaccines highlights the strong relationship existing between DM and immune system function. Clinicians should strive to achieve optimal glucose control before vaccination and promptly manage possible glucose homeostasis derangement following vaccine exposure.

The aim of the study was to evaluate the effect of metabolic syndrome (MetS) on female Swiss mice subjected to severe polymicrobial sepsis induced by cecal ligation and puncture (CLP). MetS was induced in neonatal Swiss mice by subcutaneous injection of monosodium glutamate (MSG) at 4 mg/g body weight from day 1 to day 5 after birth, while animals in the control group (CTL) were treated with equimolar saline solution at the same volume and period. On the 75th day of life, the CLP model was used to induce severe polymicrobial sepsis. For inflammatory parameters, we assessed nitric oxide (NO), determined by the cadmium/Griess technique, and quantified IL-6 and IL1β using the ELISA technique. Glucose levels were measured 24 h before and after CLP using a glucose monitor, and the lipid profile was assessed using commercial kits. Cardiovascular parameters were measured using the CODA platform, and hematological evaluation was determined by standard counting. Unlike male mice, MetS did not alter the survival of females subjected to severe sepsis. Both CTL and MetS CLP groups exhibited hypotension and hypoglycemia, accompanied by leukopenia and increased inflammatory cytokine IL-6. The cytokine IL1β Only increased in MetS CLP group compared to CTL CLP and MetS Sham. It was also observed that MetS attenuated some parameters during sepsis, such as hematological parameters and resistance to NO increase. We can conclude that the obesity paradox theory is not observed in females. Thus, our findings provide new insights for the literature linking MetS and sepsis., 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 © 2024 Elsevier Inc. All rights reserved.)

Lycium ruthenicum Murr. is mainly distributed in the northwest region of China and its berries are rich in anthocyanin. This study evaluated the hypoglycaemic activity of the anthocyanin-enriched fraction (AEF) of L. ruthenicum Murr. on α-glucosidase in vivo and in vitro. Overall, 10 anthocyanins were identified via UPLC-Triple-TOF-MS/MS. The AEF exhibited strong inhibitory activity against α-glucosidase, with an IC 50 value of 4.468 mg/mL. It behaved as a reversible, mixed-type inhibitor. Molecular docking and dynamic results indicated that the compounds in AEF interacted with enzymes primarily through van der Waals and hydrogen bond and the complex system was stable. The postprandial blood glucose and area under the curve of diabetic mice was significantly decreased by AEF in the carbohydrate tolerance experiments. The results indicate that the AEF from L. ruthenicum Murr. berries could be as a promising food supplement for managing blood sugar levels in patients with diabetes mellitus., Competing Interests: Declaration of competing interest All authors announce that they have no potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Pentachlorophenol (PCP), a ubiquitous environmental pollutant, has been reported as a possible contributor to diabetes. However, evidence for general population is scarce while related mechanisms are largely unknown. Using a representative population-based case-control study in Beijing (n = 1796), we found a positive association between PCP exposure and diabetes risk with the odds ratio reaching 1.68 (95 % confidence interval: 1.30 to 2.18). A further rat experiment revealed that low-dose PCP mimicking real-world human exposure can significantly impair glycemic homeostasis by inducing pancreatic β-cell dysfunction, with non-linear dose-response relationships. Subsequent multi-omics analysis suggested that low-dose PCP led to notable gut microbiota dysbiosis (especially the species from genus Prevotella, such as intermedia, dentalis, ruminicola, denticola, melaninogenica, and oris), decreased serum amino acids (L-phenylalanine, L-tyrosine, and L-tryptophan) and increased serum fatty acids (oleic and palmitic acid) in rats, while strong correlations were observed among alterations of gut microbes, serum metabolites and glycemic-related biomarkers (e.g., fasting blood glucose and insulin). Collectively, these results imply PCP may increase diabetes risk by disrupting gut microbial-related amino acids and fatty acids biosynthesis. This will help guide future in-depth studies on the roles of PCP in the development of human diabetes., 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 © 2024. Published by Elsevier B.V.)

Background: Diabetes mellitus is a chronic metabolic disease characterized by abnormally elevated blood glucose levels. Type II diabetes accounts for approximately 90% of all cases. Several drugs are available for hyperglycemia treatment. However, the current therapies for managing high blood glucose do not prevent or reverse the disease progression, which may result in complications and adverse effects, including diabetic neuropathy, retinopathy, and nephropathy. Hence, developing safer and more effective methods for lowering blood glucose levels is imperative. Transient receptor potential vanilloid-1 (TRPV1) is a significant member of the transient receptor potential family. It is present in numerous body tissues and organs and performs vital physiological functions., Purpose: This review aimed to develop new targeted TRPV1 hypoglycemic drugs by systematically summarizing the mechanism of action of the TRPV1-based signaling pathway in preventing and treating diabetes and its complications., Methods: Literature searches were performed in the PubMed, Web of Science, Google Scholar, Medline, and Scopus databases for 10 years from 2013 to 2023. The search terms included "diabetes," "TRPV1," "diabetic complications," and "capsaicin.", Results: TRPV1 is an essential potential target for treating diabetes mellitus and its complications. It reduces hepatic glucose production and food intake and promotes thermogenesis, metabolism, and insulin secretion. Activation of TRPV1 ameliorates diabetic nephropathy, retinopathy, myocardial infarction, vascular endothelial dysfunction, gastroparesis, and bladder dysfunction. Suppression of TRPV1 improves diabetes-related osteoporosis. However, the therapeutic effects of activating or suppressing TRPV1 may vary when treating diabetic neuropathy and periodontitis., Conclusion: This review demonstrates that TRPV1 is a potential therapeutic target for diabetes and its complications. Additionally, it provides a theoretical basis for developing new hypoglycemic drugs that target TRPV1., Competing Interests: Declaration of competing interest The authors declare not to have any conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Exposure to tobacco smoke and essential metals is linked with metabolic syndrome (MS). However, the joint effect of them on MS in older adults and the underlying mechanisms are still unclear. This large-scale study measured the urinary concentrations of 8 nicotine metabolites and 8 essential metals in 4564 older adults from Shenzhen, China. The biomarker of insulin resistance, triglyceride-glucose index (TyG), was also calculated. Restricted cubic splines (RCS), Bayesian kernel machine regression and quantile-based g-computation were used to access the single and joint effects of urinary nicotine metabolites and essential metals on MS and insulin resistance. Mediation analysis was performed to investigate the role of TyG in these relationships. Single urinary nicotine metabolite and essential metal had non-linear relationships with MS in RCS. The overall effect of urinary nicotine metabolites and essential metals was positively associated with MS. Urinary zinc (52.2 %) and copper (20.1 %) were the major contributors to MS, whereas molybdenum had a negative association with MS. TyG mediated 64.7 % of the overall effect of urinary nicotine metabolites and essential metals on MS. Overall, the mixture of urinary nicotine metabolites and essential metals had a dose-response relationship with MS. Insulin resistance was as a crucial mediated pathway in this association., 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 © 2024 Elsevier B.V. All rights reserved.)

Objective: We aim to investigate the joint effect of triglyceride-glucose (TyG) index and polygenic risk scores (PRS) of urate transporter genes ABCG2 and SLC2A9 on hyperuricemia., Methods: Baseline data from two prospective population-based cohort studies, including 30,453 individuals aged 50 years or older, were used to analyze the association between TyG index and hyperuricemia. A case-control study was then designed from the cohorts to investigate the interaction between genetic predisposition and TyG index on hyperuricemia among 595 matched pairs. PRS was constructed using 14 single nucleotide polymorphisms located in the ABCG2 and SLCA29 genes., Results: In both sexes, higher TyG index levels were correlated with elevated serum urate (SUA) levels ( p values in both sexes < 0.001). In men, per unit increase of TyG was associated with a 1.44-fold (95% confidence interval [CI]: 1.35-1.55) higher risk of hyperuricemia after adjusted for covariates. In women, this estimate was 1.69 (1.51-1.89). Demonstrated by the restrict cubic spline model, TyG index was both linearly and non-linearly associated with elevated SUA (both p values < 0.001). Association between TyG index and hyperuricemia was stronger among people with higher genetic risk, and vice versa. Compared to people with TyG < 9 and PRS < 2, the odds ratios (ORs) (95% CIs) for hyperuricemia in the TyG <9 but PRS ≥2, TyG ≥9 but PRS < 2, TyG ≥9 and PRS ≥2 groups were 3.30 (1.53-7.14), 3.16 (1.23-8.11) and 7.55 (2.76-20.65), respectively. Additive interaction was also significant, with 57.5% (30.5%-84.4%) of the excess risk attributable to the additive gene-TyG index interaction., Conclusions: The impact of genetic predisposition on hyperuricemia was significantly greater among individuals with a higher TyG index. Over 50% of the increased risk can be attributed to the interaction, indicating a crucial synergy between genetic factors and TyG index when estimating hyperuricemia risk.

Background: The regular practice of physical activity is considered a health promoter and appears to be one of the main contributors to the prevention of chronic diseases. However, the potential effects of exercise on health depending on the time of day at which it is performed have not yet been fully elucidated., Objectives: To evaluate the effect of physical exercise (aerobic or anaerobic) and chronobiology (morning or afternoon) on the glycemic metabolism of healthy subjects., Methods: Healthy subjects participated in aerobic or anaerobic physical exercise sessions, either in the morning or in the afternoon. Blood was drawn from the subjects before, at the end of the exercise and 2 hours after the end of the exercise. Glycemic parameters were analyzed at these time points. A general linear model test was performed after verifying the normal distribution of the raw data (as assessed by the Shapiro-Wilk test) or after a logarithmic/square root transformation, considering aerobic or anaerobic exercise and morning or afternoon exercise as independent variables., Results: Twenty-three subjects (14 women and 9 men) were included in the study. The rate of change in glucose levels was significantly higher at the end of anaerobic exercise compared to aerobic exercise (1.19 ± 0.04 vs. 0.98 ± 0.02, respectively), with a more pronounced decrease in insulin and C-peptide levels following aerobic exercise. In addition, the increase of glucose was higher after the exercise in the morning compared with the afternoon (1.14 ± 0.03 vs. 1.03 ± 0.03, respectively)., Conclusions: The type of exercise and chronobiology influence short-term glucose metabolism.

Background: Metabolic risk factors are a significant cause of global burden among adolescents and young adults, but there is a lack of attention to the burden attributable to these metabolic risk factors globally., Aims: This study aims to provide comprehensive estimates of five important metabolic risk factors and the attributable disease burden in people aged 15-39 years from 1990 to 2021, based on the Global Burden of Disease Study (GBD) database., Methods: Global total deaths and disability-adjusted life years (DALYs) were used to describe the burden attributable to five common metabolic risk factors, including high fasting plasma glucose (FPG), high low-density lipoprotein cholesterol (LDL-C), high systolic blood pressure (SBP), high body mass index (BMI), and kidney dysfunction, in adolescents and young adults. The estimated annual percentage changes (EAPC) of DALYs were utilized to depict the trends from 1990 to 2021., Results: From 1990 to 2021, the DALY rates attributable to all metabolic risk factors showed a globally significant upward trend, with EAPC reaching 33.0 % (27.4-38.7). Compared to females, males had a heavier burden and a more significant increase in deaths and DALYs attributable to metabolic risk factors. High BMI and high FPG have become the top two metabolic risk factors in 2021, with summary exposure variables (SEV) rising by 84.2 % and 53.6 %, respectively. Low-middle socio-demographic index (SDI), middle SDI, and high SDI regions experienced upward regional trends in DALY rates, while low SDI regions remained stable. Among 204 countries and territories, 101 (49.5 %) showed a significant increase in DALY rates, as indicated by the EAPC., Conclusions: There is a substantial global burden attributable to metabolic risk factors in adolescents and young adults in 2021, especially high BMI and high FPG. This calls for further investigation and intervention to address this emerging trend., Competing Interests: Conflict of interest Christopher D. Byrne has received grant support from Echosens. Ming-Hua Zheng has received honoraria for lectures from AstraZeneca, Hisky Medical Technologies and Novo Nordisk, consulting fees from Boehringer Ingelheim. Anoop Misra has received honoraria from Novo Nordisk, Astra Zeneca, Janssen, Lupin, Eli Lilly, US Vitamins, and Boehringer Ingelheim. Wah-Kheong Chan is a consultant or advisory board member for Abbott, Roche, Abbvie, Boehringer Ingelheim and Novo Nordisk; and a speaker for Abbott, Novo Nordisk, Echosens, Viatris and Hisky Medical. Alice P.S. Kong has received research grants and/or speaker honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Kyowa Kirin, Merck Serono, Nestle, Novo-Nordisk, Pfizer and Sanofi and Zuellig Pharma. Sander Lefere has received research grant from Inventiva. Mohit Kehar is a consultant for Mirum. Nicholas Beng Hui Ng has received honoraria from Novo Nordisk and Abbott. No other disclosures were reported., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aim: Few real-life studies have analyzed the glycemic response to nutrients in individuals without diabetes. We investigated the glycemic response to evening meals in relation to individual characteristics, nutrient components, and preprandial and postprandial routines., Methods: A cross-sectional study of 489 individuals without diabetes from a randomly selected general adult population (310 women, median age 46 years, range 18-84 years) was conducted using a continuous glucose monitoring device for 7 days. The study recorded the participants' glycemic profile at 6 h after dinner, the food consumed at dinner, the fasting duration before dinner, and the duration between the end of dinner and going to bed. Principal component analysis and multilevel functional data analysis were used to interpret the data., Results: On average, a postprandial glycemic peak was observed at 45 min, followed by a decline to baseline levels from 90 min onwards. Older age, higher body mass index, and large meals (especially those high in starch and dairy products) were all significantly associated with higher glucose levels throughout the 6 h after dinner. The fruit component was associated with a higher initial glycemic peak, followed by a lowering glycemic effect thereafter (p < 0.001). The alcohol component was associated with an initial hypoglycemic effect (p = 0.006). The participants who fasted longer before dinner had higher postprandial glycemic peaks (p = 0.001), and those who went to bed later had higher postprandial glucose levels than those who went to bed earlier (p = 0.003)., Conclusions: The participants' characteristics, nutrient components, and pre- and post-dinner routines have divergent effects on post-dinner glycemic response., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: The objective of this study was to identify sex differences in ntrahepatocellular (HCL) and intramyocardial lipids (MYCL) and cardiac function in participants with different grades of glucometabolic impairment and different BMI strata., Methods: Data from 503 individuals from 17 clinical experimental studies were analyzed. HCL and MYCL were assessed with 3T and 7T scanners by magnetic resonance spectroscopy. Cardiac function was measured with a 3T scanner using electrocardiogram-gated TrueFISP sequences. Participants were classified as having normoglycemia, prediabetes, or type 2 diabetes. Three-way ANCOVA with post hoc simple effects analyses was used for statistical assessment., Results: Consistent increases of HCL with BMI and deterioration of glucose metabolism, especially in female individuals, were detected. MYCL increased with BMI and glucose impairment in female individuals, but not in male individuals. Sex differences were found in cardiac function loss, with significant effects found among male individuals with worsening glucose metabolism. Myocardial mass and volume of the ventricle were higher in male individuals in all groups. This sex difference narrowed with increasing BMI and with progressing dysglycemia., Conclusions: Sex differences in HCL and MYCL may be associated with a higher cardiovascular disease risk observed in female individuals progressing to diabetes. Further studies are needed to elucidate possible sex differences with advancing glucometabolic impairment and obesity and their potential impact on cardiovascular outcomes., (© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Persons with long-standing, poorly controlled diabetes or recent hyperglycemia had the highest burden of cardiac autonomic neuropathy. Cardiac autonomic neuropathy contributed to elevated long-term incidence of cardiovascular disease and mortality even in persons with well-controlled diabetes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: There have been limited studies on the application of a diabetes-specific formula in gestational diabetes mellitus (GDM), the role of which has not been well studied. We explored the effect of a diabetes-specific formula on blood glucose levels, insulin use and pregnancy outcomes in GDM patients., Methods: In this randomized controlled study, 112 GDM patients were randomly assigned to the intervention group (56) and the control group (56). Both groups received individualized dietary counseling. The intervention group consumed a soy-protein-based, high-monounsaturated-fatty-acid, and multi-fiber diabetes-specific formula as milk replacement for breakfast and an extra meal after dinner. All participants were followed up every two weeks until delivery. The blood glucose levels, insulin use and pregnancy outcomes between the groups were compared., Results: Compared to the control group, the intervention group had significantly lower 2h postprandial blood glucose levels after breakfast (5.84 ± 0.56 vs. 6.15 ± 0.44 mmol/L, p = 0.008), and exhibited higher postprandial time in range values (83.80 % vs. 78.95 %, p = 0.045). The intervention group used insulin later (33 vs. 28 weeks, p = 0.015) and for fewer days (36 vs 78 days, p = 0.024), but no differences in the proportion, dose or frequency of insulin use between the groups. There were no significant differences in pregnancy outcomes between the groups., Conclusions: The diabetes-specific formula significantly decreased postprandial blood glucose levels and improved postprandial glycemic control in GDM patients. Moreover, it delayed the initiation of insulin use and reduced the duration of insulin therapy. Our findings may offer a potential new approach for achieving better personalized blood glucose control in GDM patients., Registration Number of Clinical Trial: NCT03957603 (registered at ClinicalTrials.gov)., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Pidanjiangtang (PDJT) is a traditional Chinese medicine formula empirically used to treat impaired glucose tolerance (IGT) based on the "Pidan" theory from the classic ancient book Nei Jing. However, the mechanism of PDJT intervention for IGT remains to be studied., Objective: This study aims to explore the mechanism of PDJT granules intervention in IGT by integrating gut microbiome and UHPLC-MS untargeted metabolomics., Materials and Methods: The IGT model was established in 6-week-old male Sprague-Dawley (SD) rats by feeding them a high-fat diet and using an STZ injection. The low, medium, and high doses of PDJT were used for six weeks. metformin (Glucophage) was used as the positive control drug. The efficacy of PDJT was evaluated using fasting blood glucose (FBG), blood glucose maximum (BGmax), blood lipid, and inflammatory factor levels. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PDJT intervention in IGT., Results: PDJT could reverse the phenotype of IGT rats, reduce blood glucose levels, improve lipid metabolism disorder, and reduce inflammatory response. Gut microbiome analysis found that PDJT can improve gut microbiota composition and abundance of three phyla (Firmicutes, Bacteroidota, Desulfobacterota) and four genera (unclassified&#95;f&#95;&#95;Lachnospiraceae, Ruminococcus, Allobaculum, Desulfovibrio), which play an important role in the process of PDJT intervention on glucose metabolism and lipid metabolism in IGT rats. UHPLC-MS untargeted metabolomics showed that PDJT could regulate the levels of 258 metabolites in lipid metabolism pathways, inflammatory response pathways, fat and protein digestion, and absorption. The combined analysis of the two omics showed that improving the body's metabolism by gut microbes may be the possible mechanism of PDJT in treating IGT. Thus, this study provides a new method to integrate gut microbiome and UHPLC-MS untargeted metabolomics to evaluate the pharmacodynamics and mechanism of PDJT intervention in IGT, providing valuable ideas and insights for future research on the treatment of IGT with traditional Chinese medicine., 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 © 2024 Elsevier GmbH. All rights reserved.)

Aims: The pathophysiology of diabetes is not fully understood; recent research indicates close relations with immunological alterations. Therefore, the aim of this study was to investigate the associations between markers of glucose metabolism and characteristics of blood lymphocytes in a population-based cohort., Methods: The analysis was based on data from 219 non-diabetic participants of the MEGA study in Augsburg, Germany, who were recruited between 2018 and 2021. The majority of participants were examined two different times with a time lag of 9 months. Fasting venous blood samples were taken and oral glucose tolerance tests (OGTT) were performed at both visits. Immune cells were analyzed from fresh blood using flow cytometry. The associations between fasting blood glucose levels, glucose levels at 2 h after oral glucose bolus and glycated hemoglobin (HbA1c) concentrations and the quantity of different lymphocyte subsets were analyzed using linear mixed regression models with random intercept. P values were FDR-adjusted., Results: HbA1c was negatively associated with the marginal zone B cells (IgD + CD27+ B cells). Fasting glucose was positively associated with natural killer (NK) cells and 2-h OGTT glucose was positively associated with NKT cells. Finally, HbA1c showed significantly negative associations with the CD57-PD1-NKT cell subset., Conclusion: Markers of glucose metabolism showed significant associations with B cell, NK cell and NKT cell subsets, which clearly indicates a relation between glucose metabolism and the adaptive immune system., Competing Interests: Conflict of interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Obesity is one of the leading causes of the development of insulin resistance, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) in children. With the progression of insulin resistance, both glucose and free fatty acid (FFA) plasma levels are elevated, leading to cardiometabolic complications such as impaired glucose tolerance (IGT), type 2 diabetes, and liver fat accumulation. In this study, oral minimal models were used to estimate insulin sensitivity indexes (SI and SI FFA ) in 375 adolescents with obesity. Differences between normal glucose tolerance (NGT) and IGT were assessed by using Mann-Whitney U test, while the relationship between insulin sensitivities and plasma alanine transaminase (ALT) was assessed using Spearman correlation and linear regression model of the log-transformed variables. Also, 48 youths repeated the oral glucose tolerance test and the measurement of liver function test after ∼1.3 yr of follow-up. SI was statistically different between NGT and IGT ( P < 10 -6 ) and correlated with each other (ρ = 0.7, P < 10 -6 ). Lipolysis was completely suppressed after 30 min in NGT, compared with 120 min in IGT. SI and SI FFA were both statistically correlated with ALT (ρ = -0.19, P < 10 -3 ). Also, the percentages of variation of SI FFA and ALT between the first and second visits correlated significantly (ρ = -0.47, P = 0.002). FFA minimal model can be used to estimate adipose tissue lipolysis in youths with obesity. The relationship of SI and SI FFA with ALT, along with the progression of the impairment of adipose tissue insulin sensitivity, shows that systemic insulin resistance underlies the relationship of glucose and FFA metabolism with hepatic damage. NEW & NOTEWORTHY In this study, we applied glucose, Cpeptide, and FFA minimal models to assess insulin sensitivities, insulin secretion, and lipolytic flux in NGT and IGT in adolescents with obesity. The results show that glucose and adipose tissue insulin sensitivities are strongly correlated with each other and with ALT plasma level. The longitudinal results show that changes in FFA insulin sensitivity are inversely associated with changes of beta cell secretion and with biomarkers of metabolic dysfunction-associated steatohepatitis.

Background: The prognosis of patients with coronary artery disease is adversely affected by elevated fasting plasma glucose (FPG) levels. However, the relationship between FPG levels and in-hospital cardiac arrest (IHCA) remains unclear., Objectives: The objective of this study was to investigate the association between FPG levels and IHCA in patients diagnosed with acute coronary syndrome (ACS)., Methods: Data from a total of 31,726 ACS patients fitted with inclusion and exclusion criteria across 241 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from November 2014 to July 2019 were collected. Different logistic regression models were utilized to examine the associations of FPG levels with IHCA. Sensitivity analyses were then conducted to assess the robustness of the findings. Marginal effect analyses were also employed to evaluate the impact of different therapies., Results: A total of 335 cases of IHCA and 293 in-hospital mortality were recorded throughout the study. A non-linear relationship between FPG levels and IHCA was identified after adjusting for the covariates. Specifically, a significant association was found between elevated FPG levels (≥6.1 mmol/L) and an increased risk of IHCA. These findings remained consistent across different subgroup analyses including both the diabetic and non-diabetic patients. Additionally, the marginal effect analyses revealed that percutaneous coronary intervention could lower the high FPG-related risk., Conclusions: The study findings showed a positive correlation between FPG levels and a higher incidence of IHCA, irrespective of the presence of diabetes.

Rationale: Diabetic retinopathy (DR) is linked to an increased risk of psychiatric and neurological conditions, largely due to chronic inflammation, oxidative stress, and microvascular damage associated with the disease. Emerging evidence suggests that Cassia seed extract has significant anti-inflammatory and antioxidant properties. However, the therapeutic potential of obtusin, a major compound in Cassia seed, and its underlying mechanisms remain unclear., Objective: This study aimed to evaluate the therapeutic efficacy of obtusin in the treatment of DR., Methods: Db/db mice were treated with obtusin (5 and 10 mg/kg/day) for 12 weeks. Throughout the study, body weight, blood glucose levels, and lipid profiles were monitored. Retinal histopathology and transmission electron microscopy were used to assess the pharmacological effects of obtusin in vivo. Additionally, in vitro assays were conducted on human retinal microvascular endothelial cells cultured under high glucose conditions to explore obtusin's potential role in mitigating DR., Results: Obtusin treatment in diabetic mice significantly reduced blood glucose levels, improved dyslipidemia, thickened retinal layers, reduced retinal oxidative stress, and inhibited the upregulation of inflammatory cytokines. It also lessened fundus microangiopathy and preserved the retina's normal barrier function. Mechanistic in vitro analysis suggested that obtusin targets the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway, both of which are implicated in DR., Conclusions: Our findings suggest that the Poldip2-Nox4 oxidative stress axis and the NF-κB-MAPK-VEGFA inflammatory pathway could be therapeutic targets for obtusin in the treatment of DR and its associated psychiatric and neurological conditions., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Resistance training (RT) promotes skeletal muscle (Skm) hypertrophy, increases muscular strength, and improves metabolic health. Whether changes in fat-free mass (FFM; a surrogate marker of muscle hypertrophy) moderate RT-induced improvements in glucose homeostasis has not been determined, despite extensive research on the benefits of RT for health and performance. The aim of this meta-analysis is to examine whether RT-induced Skm hypertrophy drives improvements in glucose metabolism and to explore confounders, such as biological sex and training parameters. Random-effects meta-analyses were performed using variance random effects. Meta-regressions were performed for confounding factors depending on the heterogeneity ( I 2 ). Analyses from 33 intervention studies revealed significant within-study increases in FFM with a moderate effect size (within-studies: (effect size; ES = 0.24 [0.10; 0.39]; p  = 0.002; I 2  = 56%) and a tendency for significance when compared with control groups (ES = 0.42 [-0.04-0.88]; p  = 0.07). Within-study significant increases in glucose tolerance (2 h glucose: ES = -0.3 [-0.50; -0.11]; p  < 0.01; I 2  = 43%; glucose area under the curve (AUC): -0.40 [-0.66; -0.13] I 2  = 76.1%; p  < 0.01) and insulin sensitivity (ES = 0.38 [0.13; 0.62]; I 2  = 53.0%; p  < 0.01) were also apparent with RT. When compared to control groups, there was no significant difference in 2 h glucose, nor in glucose AUC from baseline in RT intervention groups. Meta-regression analyses failed to consistently reveal increases in FFM as a moderator of glucose homeostasis. Other mixed-effect models were also unsuccessful to unveil biological sex or training parameters as moderators of FFM increases and glucose homeostasis changes. Although Skm hypertrophy and improvements in glycemic control occur concurrently during RT, changes in these variables were not always related. Well-controlled trials including detailed description of training parameters are needed to inform RT guidelines for improving metabolic health. Registration and protocol number (Prospero): CRD42023397362., Competing Interests: The authors declare no conflicts of interest.

The objective of this study was to determine if calcium propionate is an alkalizing agent in exercising Standardbreds and if it alters plasma glucose and serum insulin concentrations. This study used a randomized crossover design to test the hypotheses that calcium propionate alters total CO2 (tCO 2 ), Ca ++ , pH, strong ion difference (SID), glucose, and insulin in Standardbreds completing a simulated race test (SRT) on a high-speed equine treadmill. Blood was collected from eight horses (mean age ± SD = 16 ± 2.7 years; range = 13 - 21 years) at 10 and 5 min prior to treatment or control administration, just prior to the subsequent SRT, directly after the SRT, and at 60- and 90-min post SRT. Plasma pH and plasma concentrations of tCO 2, glucose, Ca ++ , and Na + , K + , Cl - , Lac - (for SID calculation) were measured in duplicate by blood gas analyzer and serum insulin by radioimmunoassay. Data were analyzed by two-way repeated-measures ANOVA. For plasma pH, Na + , K + , Cl - , Lac - , SID, insulin and glucose, no effects of treatment or treatment by sampling-timepoint interaction were found (p>0.05). Plasma tCO 2 , Ca ++ , pH, Na + , SID, and glucose concentrations were significantly lower, and Lac - was significantly higher, directly after the SRT compared to all other timepoints (p<0.05). Plasma tCO2, HCO 3 - and Ca ++ were significantly higher in treated than in control horses at multiple sampling timepoints after treatment/control administration (p<0.05). Serum insulin concentration, measured only pre and 30 min post treatment/control administration, was unaffected by treatment. Calcium propionate is an alkalizing agent in horses., Competing Interests: Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of this article., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Hyperglycemia is common in acute ischemic stroke, and associated with larger infarct volume and unfavorable functional outcome. To identify a subgroup that may benefit from glucose lowering in future studies, we assessed the evolution of glucose levels in the first 24 hrs after admission using continuous glucose monitoring in patients with anterior circulation large vessel occlusion ischemic stroke who underwent endovascular therapy (EVT)., Methods: In a prospective two center cohort study, consecutive patients with anterior circulation ischemic stroke, who were eligible for EVT within 24 hrs of symptom onset, were enrolled. Glucose monitoring was performed using a Freestyle Libre Flash 2 device during 24 hrs. We analysed median glucose on admission, time ratio of glucose > 7.8 mmol/L (7.8 time-ratio) and coefficient of variation (% CV), including relations with predefined patient characteristics and outcomes., Results: One hundred and two patients were included in the analyses, with a median stroke-onset-to-measurement-time of 4 hrs. Median glucose on admission was 7.0 mmol/L (IQR 6.0-8.4 mmol/L). Overall, 7.8 time-ratio and % CV were 13% and 4% respectively. In patients who were normoglycemic or hyperglycemic on admission, the glucose variability was small with % CV of 6% and 4% respectively. Hyperglycemia on admission, high HbA1C, successful recanalization, older age, and high NIHSS scores were associated with higher 7.8 time-ratio., Conclusion: Glucose monitoring and studies on effectiveness of glucose lowering may be especially useful in EVT patients with hyperglycemia on admission, high HbA1C, successful recanalization, older age and high initial NIHSS scores., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The glucose/potassium index (GPI) has been reported as a predictor biomarker of in-hospital complications in patients with aneurysmal subarachnoid hemorrhage (aSAH)., Objectives: To determine the association between GPI and functional outcome at 3-6 months after discharge in patients diagnosed with aSAH in a Peruvian referral hospital during 2018-2021., Materials and Methods: We conducted a retrospective cohort observational study with a secondary database in patients with aSAH during 2018-2021 in a Peruvian referral hospital. We evaluated the relationship between GPI values and motor functionality from 3 m to 6 months post-discharge, using a Poisson family generalized linear model with Log link function and robust variance according to categorization of good and poor outcome. We considered a value of p<0.05 as statistically significant. We used restricted cubic splines with five nodes to evaluate the linear correlation between the 2 main variables., Results: 212 patients were included in the analysis. 21.1 % and 19.3 % had poor outcome at 3 and 6 months after discharge, respectively. Multivariate analysis showed that GPI was not associated with poor outcome at 3 (RR=0.999; 95 %CI=0.979-1.018) or 6 months after discharge (RR=0.979; 95 %CI=0.979-1.020). On the other hand, Splines plots showed no correlation between GPI and modified Rankin., Conclusions: Despite the usefulness of GPI to prognosticate in-hospital complications, its association with functional outcome is inconclusive., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although numerous trials have demonstrated the benefits of purslane on patients with type 2 diabetes mellitus (T2DM), the results of some studies reject such effect. We elucidated the influence of purslane on c-reactive protein (CRP), lipid profile, and glycemic control in patients with T2DM. We conducted a systematic search on Web of Sciences, Scopus, the Cochrane Library, PubMed, and Embase, to identify studies published from their inception to February 10, 2024. The random effect model was used to calculate the combined effect, the weighted mean differences (WMDs) and its 95 % confidence interval (CI). Purslane supplementation significantly reduced fasting blood glucose (FBG) levels (WMD: -15.01; 95 % CI: -25.31, -4.71, p= 0.004), total cholesterol (TC) (WMD: -17.75; 95 % CI: -26.06, -9.45; p< 0.001), triglyceride (TG) (WMD: -21.30; 95 % CI: -32.59, -10.00; p< 0.001), low-density lipoprotein cholesterol (LDL-C) (WMD: -6.10; 95 % CI: -9.52, -2.68; p< 0.001), and CRP levels (WMD: -1.44; 95 % CI: -2.25, -0.63; p< 0.001), and increased high-density lipoprotein cholesterol (HDL-C) (WMD: 6.17; 95 % CI: 2.53, 9.80; p< 0.001). Also, purslane did not significant effect on serum levels of insulin, hemoglobin A1C (HbA1c), and homeostatic model Assessment for insulin resistance (HOMA-IR). The results of our study showed that purslane supplementation improved FBG, and lipid profile levels, but did not affect HOMA-IR, insulin, and HbA1c levels. However, high-quality trials are needed to approve our results., Competing Interests: Conflict of Interest The authors declare that they have no competing interests, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aim: Dietary shifts replacing animal protein (AP) with plant protein (PP) sources have been associated with lowering cardiometabolic risk (CMR), but underlying mechanisms are poorly characterized. This nutritional intervention aims to characterize the metabolic changes induced by diets containing different proportions of AP and PP sources in males at CMR., Design: This study is a 4-week, crossover, randomized, controlled-feeding trial in which 19 males with CMR followed two diets providing either 36 % for the control diet (CON-D) or 64 % for the flexitarian diet (FLEX-D) of total protein intake from PP sources. Plasma nontargeted metabolomes (LC-MS method) were measured in the fasted state and after a high-fat challenge meal at the end of each intervention arm. Lipogenesis and protein synthesis fluxes, flow-mediated dilatation (FMD) and gluco-lipidic responses were assessed after the challenge meal. Data were analyzed with mixed models, and univariate and multivariate models for metabolomics data., Results: In both arms CMR improved with time, with decreased body weight (-0.9 %), insulin resistant (-34 %, HOMA-IR, Homeostatic Model Assessment for Insulin Resistance) and low-density lipoproteins (LDL)-cholesterol (-11 %). Diet had no effect on FMD or metabolic fluxes, but a trend (0.05

Objective: Higher truncated-to-native apolipoprotein (apo) C-I proteoform ratios (C-I'/C-I) are associated with favorable cardiometabolic risk profiles, but their relationship with longitudinal changes in insulin resistance (IR) and incident diabetes is unknown., Research Design and Methods: Plasma apoC-I proteoforms were measured by mass spectrometry immunoassay at baseline in 4,742 nondiabetic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 524 participants with prediabetes in the Actos Now for Prevention of Diabetes (ACT NOW) study. The primary outcome was incident diabetes (fasting glucose [FG] ≥7.0 mmol/L or hypoglycemic medication use in MESA; FG ≥7.0 mmol/L or 2-h glucose ≥11.1 mmol/L in an oral glucose tolerance test [OGTT] in ACT NOW). Secondary outcomes were changes in FG and HOMA-IR in MESA, and OGTT-glucose area under the curve (AUCglucose) and Matsuda insulin sensitivity index (ISI) in ACT NOW., Results: In MESA, a higher C-I'/C-I was associated with lower risk of diabetes (n = 564 events; HR 0.87 [95% CI 0.79, 0.95] per SD; P = 0.0036; median follow-up, 9 years), and smaller increases (follow-up adjusted for baseline) in FG (-0.5%; P < 0.0001) and HOMA-IR (-2.9%; P = 0.011) after adjusting for baseline clinical and demographic covariates, including plasma triglycerides and HDL cholesterol. Total apoC-I concentrations were not associated with changes in FG, HOMA-IR, or incident diabetes. In ACT NOW, higher C-I'/C-I was associated with smaller increases in AUCglucose (-1.8%; P = 0.0052), greater increases in ISI (7.2%; P = 0.0095), and lower risk of diabetes (n = 59 events; 0.66 [95% CI 0.48, 0.91]; P = 0.004; median follow-up, 2.5 years) after adjusting for treatment group and diabetes risk factors, including plasma lipids., Conclusions: Our results indicate that apoC-I truncation may contribute to changes in glucose levels, IR, and risk of diabetes., (© 2024 by the American Diabetes Association.)

Background & Aims: Hyperglycemia is associated with an increased risk of gallbladder cancer (GBC), potentially by inhibiting gallbladder motility and inducing prolonged cholestasis. Although intermediate hyperglycemia (or prediabetes) is highly reversible, evidence is lacking about whether prediabetes persistence or remission is associated with an altered GBC risk., Methods: This nationwide cohort study included 6058,662 adults without diabetes or cancer who underwent national health examinations twice in 2-year intervals between 2009 (S1) and 2011 (S2) and were followed-up until 2018. Prediabetes was defined as a fasting plasma glucose level of 100-125 mg/dL. We categorized changes in prediabetes status into: stable normoglycemia, new-onset prediabetes, prediabetes remission, and persistent prediabetes groups. GBC risk was estimated using Cox proportional hazards models, after adjusting for potential confounders., Results: During 38.6 million person-years (median 6.4 years) of follow-up, 1349 new GBC cases were identified. Among 1409,474 individuals with prediabetes at S1, 768,515 achieved prediabetes remission at S2, outnumbering the 640,959 individuals with persistent prediabetes. GBC incidence probability was consistently higher among individuals with persistent prediabetes than in individuals with stable normoglycemia or prediabetes remission (all log-rank P < 0.01). Compared with stable normoglycemia, persistent prediabetes was associated with increased GBC risk (adjusted hazard ratio [aHR], 95 % CI: 1.21, 1.04 to 1.41). The aHRs of GBC were 1.14 (95 % CI, 0.99 to 1.33) and 1.03 (95 % CI, 0.88 to 1.21) for new-onset prediabetes and prediabetes remission, respectively., Conclusions: Individuals with persistent prediabetes had a significantly increased risk of GBC, whereas those with prediabetes remission had no increased risk. Achieving prediabetes remission has a significant potential to reduce the risk of GBC., 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 © 2024 Elsevier Ltd. All rights reserved.)

Background & Aims: The effect of lipid-lowering treatment (LLT) on metabolic dysfunction associated steatotic liver disease (MASLD) is unclear. This is relevant for patients with familial hypercholesterolemia (FH) who are on lifelong LLT. We aimed to evaluate the effect of LLT on MASLD indices in this population., Methods: Patients with at least possible diagnosis of FH were included into the Hellenic FH Registry (HELLAS-FH) registry. We analyzed the effect of statin monotherapy, statin/ezetimibe and statin/ezetimibe/proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) on MASLD indices, i.e., original triglyceride-glucose index (TyGO) and triglyceride-glucose index (TyG). We compared changes of TyG and TyGO before any treatment and after at least one year of stable LLT., Results: We included 1289 patients: n = 569 in the statin monotherapy group (mean age = 51 ± 15 years, 52.7 % males), n = 629 in the statin/ezetimibe group (52 ± 14 years, 51.8 %), and n = 91 in the statin/ezetimibe/PCSK9i group (54 ± 13 years, 58.2 %). Compared with baseline, TyGO and TyG decreased significantly following statin monotherapy (8.61 vs 8.49 and 4.65 vs 4.59, respectively, both p < 0.01), statin/ezetimibe (8.59 vs 8.41 and 4.64 vs 4.55, respectively, both p < 0.01) and statin/ezetimibe/PCSK9i (8.79 vs 8.55 and 4.74 vs 4.62, respectively, both p < 0.01). There was no difference regarding the change of TyGO and TyG between groups after adjusting for baseline levels. A greater percentage of patients in the statin/ezetimibe and statin/ezetimibe/PCSK9i groups exhibited TyGO-defined MASLD resolution compared with statin monotherapy (p < 0.05). After adjustment for possible confounders, LLT was significantly associated with MASLD resolution., Conclusions: MASLD indices were significantly improved in all LLT groups in FH patients. Statin/ezetimibe and statin/ezetimibe/PCSK9i were associated with greater TyGO-defined MASLD resolution compared with statin monotherapy., Competing Interests: Conflict of interest CB, CVR, GL, AG, GS, PA, VK, GA, EP, CV, ID, FG, KAP, AA, VK, CK, DA, CA has nothing to declare. IS has given talks, received honoraria, and participated in clinical trials sponsored by MSD, AMGEN, SANOFI. LR has received research grants and honoraria from Amgen, Sanofi-Aventis, Viatris, Novartis, Vianex and Servier. GK has given talks, attended conferences and participated in trials sponsored by Amgen, Angelini, MSD, Lilly, Vianex and Sanofi and has also accepted travel support to conferences from Amgen, Sanofi and MSD. KT has participated in educational, research and advisory activities sponsored by AMGEN, ANGELINI, ASTRA-ZENECA, BAYER, BOEHRINGER-INGELHEIM, ELPEN, LILLY, MSD, MYLAN, NOVO NORDISK, SANOFI and VIANEX. ES has participated in educational and advisory activities sponsored by AstraZeneca, Medtronic, MSD, Sanofi and Servier. VK has given talks and attended conferences sponsored by AstraZeneca, MSD, Sanofi-Aventis, and Vianex. MD has participated in educational, research and advisory activities sponsored by Menarini, Elpen, AstraZeneca, MSD, Bayer, Sanofi, Novartis, and Servier. KS has received honoraria from Amgen. VL has given lectures, attended conferences and participated in trials sponsored by Novo Nordisk, Sanofi-Aventis, Novartis, AstraZeneca, Boehringer-Ingelheim, MSD, GSK, Vianex, Elli Lilly, ELPEN, Mylan and Aegereon. AB has received honoraria from Vianex, Amarin and Sanofi. EL has participated in educational, research and advisory activities sponsored by AstraZeneca, MSD, Lilly, Bayer, Amgen, Sanofi, Boehringer-Ingelheim, Novartis, Novo Nordisk, Valeant and Servier. EZ has received honoraria for lectures from Amgen. Sanofi, MSD, and Astra Zeneca. HM participated in educational, research and consulting activities supported by healthcare companies, including Amgen, AstraZeneca, Boehringer Ingelheim, Elpen, Novartis, Sanofi, Vianex, Ultragenyx, Winmedica. EL has participated in educational, research and advisory activities sponsored by AstraZeneca, MSD, Lilly, Bayer, Amgen, Sanofi, Boehringer-Ingelheim, Novartis, Novo Nordisk, Valeant and Servier. CSM reports grants through his institution from Merck, Massachusetts Life Sciences Center, and Boehringer Ingelheim, has been a shareholder of and has received grants through his institution and personal consulting fees from Coherus Inc. and AltrixBio; he reports personal consulting fees and support with research reagents from Ansh Inc., collaborative research support from LabCorp Inc., reports personal consulting fees from Genfit, Lumos, Amgen, Corcept, Aligos, Intercept, 89 Bio, Madrigal, and Regeneron, reports travel support and fees from TMIOA, Elsevier, and the Cardio Metabolic Health Conference. None is related to the work presented herein. ENL has participated in educational, research and advisory activities sponsored by AstraZeneca, MSD, Lilly, Bayer, Amgen, Sanofi, Boehringer Ingelheim, Novartis, Novo Nordisk, Valeant and Servier., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: To compare the risk of hospitalization for infection among patients who achieve intensive versus relaxed glycemic control., Research Design and Methods: This retrospective cohort study included adults age ≥65 years with type 2 diabetes from an integrated health care delivery system. Negative binomial models were used to estimate incidence rates and relative risk (RR) of hospitalization for infections (respiratory; genitourinary; skin, soft tissue, and bone; and sepsis), comparing two levels of relaxed (hemoglobin A1c [HbA1c] 7% to <8% and 8% to <9%) with intensive (HbA1c 6% to <7%) glycemic control from 1 January 2019 to 1 March 2020., Results: Among 103,242 older patients (48.5% with HbA1c 6% to <7%, 35.3% with HbA1c 7% to <8%, and 16.1% with HbA1c 8% to <9%), the rate of hospitalization for infections was 51.3 per 1,000 person-years. Compared with HbA1c 6% to <7%, unadjusted risk of hospitalization for infections was significantly elevated among patients with HbA1c 8% to <9% (RR 1.25; 95% CI 1.13, 1.39) but not among patients with HbA1c 7% to <8% (RR 0.99; 95% CI 0.91, 1.08), and the difference became nonsignificant after adjustment. Across categories of infections, the adjusted RR of hospitalization was significantly higher among patients with HbA1c 8% to <9% only for skin, soft tissue, and bone infection (RR 1.33; 95% CI 1.05, 1.69)., Conclusions: Older patients with type 2 diabetes who achieve relaxed glycemic control levels endorsed by clinical guidelines are not at significantly increased risk of hospitalization for most infections, but HbA1c 8% to <9% is associated with an increased risk of hospitalization for skin, soft tissue, and bone infections., (© 2024 by the American Diabetes Association.)

Background: Diabetic cardiomyopathy (DCM) is one of the leading causes of death in patients with diabetes mellitus (DM). This study aimed to identify a reliable method for establishing an animal model of DCM for investigation of new targets and treatments., Methods: Eighty-four 4-week-old male Sprague-Dawley rats were randomly allocated to receive a normal diet or a high-fat diet (HFD) in an approximate ratio of 1:3. At 9 weeks of age, rats in the HFD group received streptozotocin (STZ) 30 mg/kg by intraperitoneal injection and rats in the control group received the same volume of buffer solution. The rodent model of DM was deemed to be successfully established when a random blood glucose measurement was >16.7 mmol/L on three consecutive occasions. If necessary, STZ was readministered., Results: Three of the 64 rats in the HFD group died after a second STZ injection. DM was induced in 14, 39, and 8 rats after one, two, and three injections, respectively, with cumulative success rates of 21.9 %, 82.8 %, and 95.3 %. Three months later, the rats with DM showed persistent hyperglycemia and insulin resistance and developed histopathological changes indicating cardiac hypertrophy, myocardial fibrosis, and diastolic dysfunction. The metabolic and cardiac histopathological changes were consistent regardless of whether DM was induced by one, two, or three injections of STZ., Conclusion: An HFD combined with one or more intraperitoneal injections of low-dose STZ is a straightforward and reliable method for inducing DCM in rats. When a single dose of STZ fails to induce DM, repeated injections can be considered., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Exercise is an essential component of body mass management interventions. Overnight-fasted exercise (FASTex) acutely enhances fat oxidation compared with fed exercise (FEDex). However, consistent FASTex training does not typically further enhance body mass loss, suggesting the induction of energy compensation responses. The present study aimed to test the effects of FASTex or FEDex on the components of energy balance (i.e., energy intake (EI), energy expenditure (EE), and appetite) and interstitial glucose metrics across four days., Methods: Twelve (10 men, 2 women) healthy, physically active participants (age 22.6 + 1.2 years (mean ± SD); BMI 22.5 ± 2.8 kg ⋅ m -2 ) were studied twice, across four days, after a 75-min run either FASTex or FEDex. Daily EI was obtained after subtracting leftovers from the provided food. Daily fasting appetite was measured by visual analogue scales. Activity- and total- EE (AEE & TEE, respectively) were estimated by combining heart rate and accelerometry. Continuous glucose monitoring was used to capture daily interstitial glucose metrics and Likert scales were utilised to quantify fatigue, stress, sleep quality, and muscle soreness levels., Results: No differences between conditions were observed for EI (FASTex = 15.0 ± 0.1 vs FEDex = 15.0 ± 0.4 MJ⋅day -1 ; p = 0.865), AEE (FASTex = 7.6 ± 1.1 vs FEDex 7.8 ± 1.3 MJ⋅day -1 ; p = 0.223) and TEE (FASTex = 15.9 ± 3.4 vs 14.9 ± 4.5 MJ⋅day -1 ; p = 0.136). Additionally, no condition effects for appetite (p > 0.05) and interstitial glucose (p = 0.074) were observed., Conclusion: FASTex did not differ from FEDex in the response of components of energy balance or interstitial glucose across four days, suggesting that both exercise approaches could be used interchangeably., 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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Accumulation of circulating branched-chain amino acids (BCAA) is a hallmark feature of impaired insulin sensitivity. As intracellular BCAA catabolism is dependent on glycine availability, we hypothesised that the concurrent measurement of circulating glycine and BCAA may yield a stronger association with markers of insulin sensitivity than either BCAA or glycine alone. This study therefore examined the correlative relationships of BCAA, BCAA and glycine together, plus glycine alone on insulin sensitivity-related markers before and after an 8-week low energy diet (LED) intervention., Methods: This is a secondary analysis of the PREVIEW (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World) Study New Zealand sub-cohort. Eligible participants with pre-diabetes at baseline who achieved ≥8 % body weight loss following an LED intervention were included, of which 167 paired (Week 0 and Week 8) blood samples were available for amino acid analysis. Glycemic and other data were retrieved from the PREVIEW consortium database. Repeated measures linear mixed models were used to test the association between amino acids and insulin sensitivity-related markers (HOMA2-IR, glucose, insulin, and C-peptide)., Results: Elevated BCAA was associated with impaired insulin sensitivity (p < 0.05), with strength of association (ηp2) almost doubled when glycine was added to the model. However, glycine in isolation was not associated with insulin sensitivity-related markers. The magnitude (β-estimates) of positive association between BCAA and HOMA2-IR, and inverse association between glycine and HOMA2-IR, increased when body weight was higher (Body weight∗BCAA, Body weight∗glycine, p < 0.05, both)., Conclusion: Low serum glycine strengthened the association between BCAA and impaired insulin sensitivity. Given that glycine is necessary to facilitate intracellular BCAA catabolism, measurement of glycine is necessary to complement BCAA analysis to comprehensively understand the contribution of amino acid metabolism in insulin sensitivity., Clinical Trial Registration: This study was registered with ClinicalTrials.gov (NCT01777893)., Competing Interests: Conflict of interest SDP was the Fonterra Chair in Human Nutrition during the PREVIEW intervention; AR has received honorariums from Nestle, Unilever and the International Sweeteners Association. Other authors declare no relevant competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The present study aimed to investigate the effect of swimming training on the angiogenesis of endothelial progenitor cells (EPCs) in type 2 diabetes mellitus (T2DM) rats by upregulating the insulin‑like growth factor 1 (IGF1) expression and to reveal its potential mechanism of action. Male Sprague‑Dawley rats were divided into the Control, Model, Model train, Model train + short interfering (si)‑NC and Model train + si‑IGF1 groups. Serum glucose levels were measured using the oral glucose tolerance test. EPCs were isolated from the bone marrow cavity and identified through morphological observation and immunofluorescence staining. The expression of IGF‑1 mRNA in rat serum and EPCs was analyzed by reverse transcription‑quantitative PCR. The fasting insulin levels in serum were assessed by ELISA. Cell Counting Kit‑8, scratch assay and tube formation assay were used to determine the cell viability, migration and tube formation of rat EPCs, and western blotting was employed to measure the expression levels of IGF1, phosphoinositide 3‑kinase (PI3K), phosphorylated‑PI3K, protein kinase B (AKT) and phosphorylated‑AKT. The present study demonstrated that swimming training significantly decreased the glucose levels and homeostatic model assessment of insulin resistance scores, but increased the fasting insulin levels and IGF1 mRNA expression. Microscopic observation and immunofluorescence identification suggested that EPCs were successfully isolated. In addition, swimming training markedly elevated the levels of IGF1 and promoted cell viability, migration and tube formation in rat EPCs. Furthermore, IGF1 knockdown experiments indicated that swimming training might play a regulatory role by elevating the IGF1 expression to activate the PI3K/AKT pathway. Overall, swimming training promoted the angiogenesis of EPCs in T2DM rats and its potential mechanism may be related to the upregulation of IGF1 expression and the activation of the PI3K/AKT pathway.

Objective: Gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth as measured by two-dimensional ultrasonography. Whether fetal three-dimensional (3D) soft tissue and organ volumes provide additional insight into fetal overgrowth is unknown., Research Design and Methods: We prospectively evaluated longitudinal 3D fetal body composition and organ volumes in a diverse U.S. singleton pregnancy cohort (2015-2019). Women were diagnosed with GDM, impaired glucose tolerance (IGT), or normal glucose tolerance (NGT). Up to five 3D ultrasound scans measured fetal body composition and organ volumes; trajectories were modeled using linear mixed models. Overall and weekly mean differences in fetal 3D trajectories were tested across glycemic status, adjusted for covariates., Results: In this sample (n = 2,427), 5.2% of women had GDM, and 3.0% had IGT. Fetuses of women who developed GDM compared with NGT had larger fractional arm and fractional fat arm volumes from 26 to 35 weeks, smaller fractional lean arm volume from 17 to 22 weeks, and larger abdominal area from 24 to 40 weeks. Fetuses of women with IGT had similar growth patterns, which manifested later in gestation and with larger magnitudes, and had larger fractional lean arm volume. No overall differences were observed among thigh or organ volumes across glycemic status., Conclusions: Body composition differed in fetuses of GDM-complicated pregnancies, including larger arm and abdominal measures across the second and third trimesters. Patterns were similar in IGT-complicated pregnancies except that they occurred later in gestation and with larger magnitudes. Future research should explore how lifestyle and medication may alter fetal fat accumulation trajectories among hyperglycemic pregnancies., (© 2024 by the American Diabetes Association.)

Background: Continuous Glucose Monitoring (CGM) provides a detailed representation of glucose fluctuations in individuals, offering a rich dataset for understanding glycemic control in diabetes management. This study explores the potential of Riemannian manifold-based geometric clustering to analyze and interpret CGM data for individuals with Type 1 Diabetes (T1D) and healthy controls (HC), aiming to enhance diabetes management and treatment personalization., Methods: We utilized CGM data from publicly accessible datasets, covering both T1D individuals on insulin and HC. Data were segmented into daily intervals, from which 27 distinct glycemic features were extracted. Uniform Manifold Approximation and Projection (UMAP) was then applied to reduce dimensionality and visualize the data, with model performance validated through correlation analysis between Silhouette Score (SS) against HC cluster and HbA1c levels., Results: UMAP effectively distinguished between T1D on daily insulin and HC groups, with data points clustering according to glycemic profiles. Moderate inverse correlations were observed between SS against HC cluster and HbA1c levels, supporting the clinical relevance of the UMAP-derived metric., Conclusions: This study demonstrates the utility of UMAP in enhancing the analysis of CGM data for diabetes management. We revealed distinct clustering of glycemic profiles between healthy individuals and diabetics on daily insulin indicating that in most instances insulin does not restore a normal glycemic phenotype. In addition, the SS quantifies day by day the degree of this continued dysglycemia and therefore potentially offers a novel approach for personalized diabetes care., 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 © 2024 Elsevier Ltd. All rights reserved.)

Aims: Dietary fiber (DF) can be separated from food and convenient to take, and has an important role in diabetes prevention, but long-term intervention data are lacking. This study evaluated the long-term benefits of DF supplementation on body composition, glucose-lipid metabolism, and clinical regression in middle-aged and elderly patients with prediabetes., Methods: A randomized, controlled, open clinical study was conducted. Participants were randomized into a control group receiving health education and an intervention group consuming DF supplements daily before meals (15 g of mixed fiber per serving) for 6 consecutive months based on health education. Follow-up was 1 year with a 6-month cycle. Blood and anthropometric parameters were assessed at baseline and 6 months and 12 months of follow-up., Results: Fifty-four participants were included in the study, 27 in each group. After 6 months, waist circumference, waist-to-hip ratio, fasting plasma glucose (FPG), 2 hour plasma glucose (2h PG), and postprandial insulin levels were significantly lower in the intervention group compared to baseline. FPG, 2h PG, glycosylated hemoglobin, triglyceride/high-density lipoprotein cholesterol values and diabetes incidence were lower than in the control group. After 12 months, blood glucose and diabetes incidence remained lower in the intervention group., Conclusions: DF supplementation can reduce the degree of central obesity, the levels of FPG and 2h PG, and the incidence of diabetes in middle-aged and older patients with prediabetes., Competing Interests: Declaration of competing interest The authors declare no financial or other conflicts of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The brain coordinates the homeostatic defense of multiple metabolic variables, including blood glucose levels, in the context of ever-changing external and internal environments. The biologically defended level of glycemia (BDLG) is the net result of brain modulation of insulin-dependent mechanisms in cooperation with the islet, and insulin-independent mechanisms through direct innervation and neuroendocrine control of glucose effector tissues. In this article, we highlight evidence from animal and human studies to develop a framework for the brain's core homeostatic functions-sensory/afferent, integration/processing, and motor/efferent-that contribute to the normal BDLG in health and its elevation in diabetes., (© 2024 by the American Diabetes Association.)

Objectives: The aim of this study was to investigate whether periodontal condition is associated with the development of impaired glucose tolerance (IGT)., Material and Methods: This study was based on a subpopulation of a cohort of persons born in 1935 and living in Oulu, Finland, on October 1, 1990. The participants were normoglycemic (no previously diagnosed diabetes mellitus and a 2-h oral glucose tolerance test [OGTT] blood glucose < 7.8 mmol/L) in the baseline examinations (1990-1992) and had fasting blood glucose < 7.0 mmol/L in the follow-up examinations (2007-2008) (n = 225). The outcome was IGT on follow-up, measured by a blood glucose level of ≥ 7.8 mmol/L after OGTT. The exposure was the periodontal condition at baseline categorized into four groups: 0, 1-6, ≥ 7 sites with deepened (≥ 4 mm) periodontal pockets, and edentulousness., Results: A total of 23% of the participants developed IGT. The adjusted incidence rate ratios with 95% confidence intervals (CI) for dentate participants with 1-6 sites and ≥ 7 sites with deepened periodontal pockets, and edentate participants (reference category dentate participants without deepened periodontal pockets) were 1.5 (95% CI, 0.6-4.0), 1.8 (95% CI, 0.7-4.4), and 1.6 (95% CI, 0.6-4.0), respectively., Conclusions: Poor periodontal condition may predispose individuals to IGT; however, further studies on this matter are warranted., (© 2024 The Author(s). Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Aims: Both erectile dysfunction (ED) and diabetes (DM) are common health problems that share risk factors. The aim of this study was to investigate whether ED can predict glucose metabolism dysfunctions in men at the primary care level., Methods: An 11-year population-based cohort study was conducted in men born between 1933 and 1956. The baseline survey was conducted in 2007-2008, with a follow-up examination 11 years later. The International Index of Erectile Function (IIEF-5) questionnaire was used to assess erectile function. Dysglycemia was evaluated using and a 2-hour oral glucose tolerance test (2hOGTT), in combination with health registry data., Results: At baseline, men with ED but without a history of known DM exhibited a significantly higher prevalence of undetected DM, odds ratio (OR) 4.7 (95 % CI 1.6, 14.4), and preDM, OR 1.9 (1.1, 3.2), compared with men without ED. Over an 11-year follow-up period, a significantly increased cumulative incidence of DM was observed in men who reported symptoms of ED at the start of the study., Conclusions: The symptoms of ED appear to be an early warning sign of existing DM and preDM and predict an increased risk of developing abnormal glucose metabolism in the future., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: The triglyceride-glucose (TyG) index, a novel reliable biomarker for IR that incorporates blood glucose and triglyceride, is linked to intracranial atherosclerotic stenosis (ICAS). In this study, we aimed to further investigate the association between the TyG index and the outcomes of ICAS patients following extracranial-to-intracranial (EC-IC) bypass grafting., Methods: 489 ICAS patients who underwent EC-IC bypass between Jan 2009 and Jan 2022 at our hospital were retrospectively collected. The major adverse cardiac and cerebrovascular events (MACCEs), and anastomotic restenosis, both of which are critical factors leading to poor prognosis of ICAS patients after EC-IC bypass, were mainly recorded and analyzed. Kaplan-Meier survival curve and Log-rank tests were sequentially conducted. Cox regression model was used to investigate the association between the TyG index and MACCEs & anastomotic stenosis. C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI) evaluated the incremental predictive value of the TyG index., Results: A higher incidence of MACCEs and anastomotic stenosis was found in higher-tertile TyG index group. The TyG index was significantly associated with an increased risk of MACCEs and anastomotic stenosis, independent of confounding factors, with a value of HR (1.30, 95%CI 1.10-1.51, p  < 0.001) and (1.27, 95%CI 1.16-1.40, p  < 0.001) respectively. The area under the curve (AUC) in the model with the TyG index for predicting the occurrence of MACCEs and anastomotic stenosis were 0.708 (95%CI 0.665-0.748) and 0.731 (95%CI 0.689-0.770) respectively. The addition of the TyG index significantly improved the global performance of the baseline model according to the C-statistics, NRI, and IDI (All p  < 0.05)., Conclusions: Higher TyG levels were associated with poorer outcomes in ICAS patients after EC-IC bypass. TyG could be a key factor in managing ICAS risk and standardizing the indications for EC-IC bypass.

Background: Diabetes mellitus represents a prominent global health concern, characterized by a rising prevalence rate. Type 2 Diabetes Mellitus (T2DM) is purported to be associated with an intricate interplay of genetic, environmental, and lifestyle factors. While some progress have been made in T2DM management, controlling associated complications remains a great challenge in medicine., Objectives: This study investigated a synthesized Imidazolyl Thiazolidinedione antidiabetic agent (PA9), focusing on serum parameters., Methods: Streptozotocin-induced diabetic rats (n = 6) were subjected to orally treatment with PA9 (synthesized by Shakour et al. in an equal dose of a standard drug, 0.011 mmol/kg). The study conducted to measure some specific serum factors, including lipid profiles, liver and kidney enzymes, cardiac enzymes, and oxidative stress markers, both before and after treatment., Results: The study findings indicated that PA9 effectively ameliorates hyperlipidemia by significantly reducing total cholesterol and triglyceride levels in serum. Additionally, PA9 demonstrated hepatoprotective effects against TZD-induced injuries, as evidenced by decreased levels of alanine transaminase and, alkaline phosphatase. In addition, PA9 also exhibited a modulatory effect on a cardiac injury marker, creatine kinase MB. Moreover, PA9 demonstrated antioxidant properties by reducing oxidative stress markers and enhancing the activities of catalase, thiol, and superoxide dismutase., Conclusions: The synthesized TZD compound (PA9) stands out as a highly promising agent for the management of diabetes. Its significant antihyperlipidemic effects, preventive influences on organ injuries, and demonstrated efficacy in reducing oxidative stress marker (SOD) make it therapeutic agent in diabetes management. This study lays the groundwork for innovative strategies in diabetes management., Competing Interests: Declaration Conflict of interests The authors declare that they have no conflicts of interest. Ethical approval The ethical clearance for the animal experimentation was obtained from the Ethics Committee at Mashhad University of Medical Sciences, with approval referenced as IR.MUMS.SP.1396.196., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Aims: To describe the development of a culturally adapted, evidence-based, and theory-driven diabetes self-management programme for Chinese adults with type 2 diabetes receiving insulin injection therapy and to assess the feasibility, acceptability, and preliminary effects of the newly developed intervention., Methods: The Medical Research Council framework was adopted to guide the intervention development and a feasibility study. A prospective, two-arm, parallel-group, assessor-blinded randomised controlled trial was conducted. Participants were randomly allocated to receive either the newly developed intervention or parallel attention control contact from community nurses. Between-group differences in changes in outcome variables were analysed using the Mann-Whitney U test., Results: The newly developed intervention consists of one individual interview session, three group-based education sessions, and two telephone-based maintenance sessions. A total of 24 participants were recruited with the recruitment rate and overall retention rate of 77.4 % and 95.8 %, respectively. The results indicated that the intervention participants reported significantly greater improvements in self-efficacy (Hedge's g = 1.69) and self-management behaviours (Hedge's g = 3.24), and reductions in diabetes-related distress (Hedge's g = 1.49) compared with those in the control group (all p< 0.05)., Conclusion: The diabetes self-management programme was feasible and acceptable. The intervention showed promising patient-centred benefits. A future large-scale randomised controlled trial is warranted., 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 © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

The aim of the present work was to gain insight into the metabolism of pigs derived from assisted reproductive technologies during their adulthood. Approximately 4h after feeding, a blood sample was taken from 3.5 year old sows born by artificial insemination (AI group, n = 7) and transfer of in vitro produced embryos (IVP group, n = 11) to determine the physiological concentrations of the main biomarkers of carbohydrates (glucose and lactate), proteins (albumin, creatinine and urea) and lipids (cholesterol and triglycerides). Four weeks later, an oral glucose tolerance test (OGTT; 1.75g glucose/kg body weight) was performed after an overnight fast and 1h of water withdrawal. Blood samples were obtained prior (T = 0 min; fasting conditions) and 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min after glucose intake. At each time point, glycemia was measured immediately using glucometer test strips, and serum was collected to determine the above metabolites along with insulin and glucagon. After OGTT, the area under the curve (AUC) between sampling times and homeostasis model assessment of insulin resistance (HOMA) indices were calculated. Under physiological conditions, the concentration of metabolites studied was similar between AI and IVP sows. In both groups, fasting decreased cholesterol and increased triglycerides and urea (P < 0.001). However, creatinine and lactate were similar in both groups under physiological and fasting conditions. The expected increase in albuminemia and decrease in glycaemia after fasting was only observed in IVP sows. OGTT revealed a different glucose curve pattern (monophasic in AI and biphasic in IVP group), a lower mean concentration of cholesterol, glucose, lactate, triglycerides in IVP compared to AI pigs (P < 0.01), and a higher mean concentration of albumin, creatinine and insulin in IVP compared to AI group (P < 0.05). On the contrary, no differences were found between groups for mean serum glucagon and urea levels, nor for glucose homeostasis indices HOMA-IR and HOMA-%B. The AUC differed between groups at several time points with larger AUC for creatinine, and smaller AUC for glucose, glucagon, and triglycerides, in IVP pigs than in AI pigs at 180-210 min (P < 0.05). In conclusion, under physiological conditions the metabolic profile of fully-grown AI and IVP sows is similar and within normal ranges. Glucose challenge revealed differences in metabolic and insulin responses between groups but with normal glucose tolerance in both cases., Competing Interests: Declaration of interest None of the authors have any conflict of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Previous research has suggested a correlation between fine particulate matter (PM2.5) and type 2 diabetes mellitus (T2DM). However, the causality was vulnerable to confounding variables., Methods and Results: A two-sample multivariable mendelian randomization study was designed to examine the causal connection between PM2.5 and T2DM. PM2.5 trait was investigated as exposure while T2DM-related traits as outcomes. The summary data were obtained from the Finngen database and the open genome-wide association study database. The mendelian randomization estimates were obtained using the inverse-variance weighted approach, and multiple sensitivity analyses were conducted. There were potential causal relationships between PM2.5 and T2DM (OR = 2.418; P = 0.019), PM2.5 and glycated hemoglobin (HbA1c) (OR = 1.590; P = 0.041), and PM2.5 and insulin metabolism. PM2.5 was found to have no causal effect on fasting glucose and insulin, 2-h glucose, and insulin-like growth factor binding protein-1 (P > 0.05), while had a potential protective effect against some diabetes complications., Conclusions: Our findings indicated potential causal relationships among PM2.5 and T2DM, especially the causal relationship between PM2.5 and long-term glucose levels., Competing Interests: Declaration of competing interest 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction/aims: Changes in body composition in patients with spinal muscular atrophy (SMA) can cause endocrine abnormalities that are insufficiently studied in adults. We aimed to assess the endocrine profile in a cohort of adults with SMA. Second, we compared body composition and endocrine profiles between nonambulatory and ambulatory patients and between different types of SMA., Methods: The cross-sectional study included 29 SMA patients (18 [62.1%] males and 11 [37.9%] females) of median age 44 (IQR 30-51.5) years with type 2, 3, or 4. Body composition was measured by bioimpedance. Morning blood samples were drawn for glycated hemoglobin (HbA1c), lipid profile, testosterone, cortisol, and insulin-like growth factor-1 (IGF-1). Blood glucose, insulin, and beta-hydroxybutyrate (BHB) were measured during a 75 g oral glucose tolerance test. The homeostatic model assessment for insulin resistance index was calculated., Results: In total, 75.9% of patients had increased fat mass (FM), with 51.7% having an increase despite normal body mass index. Ambulation was the most important discriminating factor of body composition. 93.1% of patients had metabolic abnormalities, including hyperglycemia, insulin resistance, and dyslipidemia. Increased BHB, a marker of ketosis, was present in more than a third of patients. Functional hypogonadism was present in half of male patients. Testosterone and IGF-1 negatively correlated with FM., Discussion: Adult patients with SMA had abnormal body composition and highly prevalent metabolic disturbances that might increase cardiometabolic risk. Because treatments have modified the course of SMA, it is important to investigate whether these observations translate into clinically relevant outcomes., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Background: Whether the cardiovascular treatment benefits of sodium-glucose co-transporter 2 inhibitors (SGLT-2is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) differ by baseline use of statins/lipid lowering therapy is unclear. This systematic review and meta-analysis investigated whether baseline statin use (users vs non-users) influences the cardiovascular and kidney benefits of SGLT-2is and GLP-1RAs in patients with type 2 diabetes (T2D)., Methods: We identified relevant cardiovascular outcome trials (CVOTs) and observational cohort studies from MEDLINE, Embase, the Cochrane Library, and bibliographic searches up to March 2024. The analysis pooled study-specific hazard ratios (HRs) with 95 % confidence intervals (CIs) for outcomes, categorized by baseline statin use status. We also assessed the interactions between these medications and baseline statin use by calculating and pooling the ratio of HRs (RHRs) within each trial., Results: Twenty-five articles (13 articles comprising 6 unique CVOTs and 12 articles comprising 9 unique cohort studies) were eligible. In CVOTs of SGLT-2is, the HRs (95 % CIs) of MACE; composite of CVD death or hospitalisation for heart failure; stroke; and kidney events in statin users were 0.90 (0.82-1.00), 0.78 (0.60-1.02), 1.00 (0.77-1.31), and 0.60 (0.53-0.69), respectively. The corresponding estimates were similar in non-statin users. In CVOTs of GLP-1RAs, the HRs (95 % CIs) for MACE in statin and non-statin users were 0.81 (0.73-0.90) and 0.92 (0.77-1.11), respectively. In observational cohort studies, SGLT-2is similarly reduced the risk of several cardiovascular and kidney outcomes in both statin and non-statin users. The estimated RHRs and p-values for interaction indicated that baseline statin use status did not significantly modify the cardio-kidney benefits of SGLT-2is and GLP-1RAs., Conclusions: Aggregate analyses of intervention and real-world evidence show that SGLT-2is and GLP-1RAs provide comparable cardio-kidney benefits in patients with T2D, regardless of baseline statin use status. PROSPERO Registration: CRD42024498939., Competing Interests: Declaration of Competing Interest SS is in receipt of speaker honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, MSD, Abbott, Novo Nordisk, SB Communications, OmniaMed Communications, Roche, Napp Pharmaceuticals, NB Medical and Amgen; advisory board honoraria from AstraZeneca, Lilly, Boehringer Ingelheim, Janssen, Abbott, MSD, Novo Nordisk, Takeda and Sanofi; educational grants from Boehringer Ingelheim, Lilly, Novo Nordisk, and Takeda; and conference registration and subsistence from Boehringer Ingelheim, Janssen, Lilly, Novo Nordisk, Abbott and Takeda. BSS and SKK have no conflicts, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The present study investigated the effect of low vs high-dietary-Advanced Glycation End products-based diets on oral disposition index-(DIo)-a marker of islet β-cell function and cardiometabolic risks factors in 38-overweight and obese Asian Indian-adults (aged 25-45 years with body-mass-index (BMI) ≥23kg/m 2 ) through 12-week isocaloric crossover feeding trial. Biochemical-measures included-glucose tolerance test (GTT), Insulin assay (0,30 and 120 min), lipid-profile, serum-adiponectin, serum-AGE and serum-Thiobarbituric acid reactive substances-(TBARS) assessed both at baseline and end of each intervention. Generalised linear models showed that low-dAGE diet significantly improved in oral disposition index [Least Square Mean (SE), +0.3 (0.1); p =  0.03] compared to high-dAGE diet. The low-dAGE diet also showed a significant reduction in 30-minutes plasmapost-glucose-challenge-value:(-8.1[3.8] (mg/dl) vs 3.8 [3.8] (mg/dl); p  = 0.01), serum-AGEs-(-3.2 [0.2] (μg/ml) vs -0.8 [0.2] (μg/ml); p = <0.0001) compared to high-dAGE diet. In summary, low-dAGE diets exhibited improvement in the insulin-sensitivity and reduction in the inflammatory levels compared to high-dAGE diets. Hence, study first time in India revealed that low dAGE diets could be a potential strategy to reduce diabetes risk.

Aim: To compare the effects of iGlarLixi versus insulin glargine 100 U/mL (iGlar) on residual hyperglycaemia in Chinese people with uncontrolled type 2 diabetes (T2D) on prior basal insulin (BI) therapy ± oral antidiabetic drugs in the LixiLan-L-CN study (NCT03798080)., Materials and Methods: In this post hoc analysis, residual hyperglycaemia (i.e. HbA1c ≥ 7.0% [≥ 53 mmol/mol] and fasting plasma glucose [FPG] < 7.0 mmol/L) were assessed over 30 weeks. Outcomes were assessed at week 30 in participants with baseline residual hyperglycaemia, including changes from baseline in HbA1c, FPG, 2-hour postprandial glucose (PPG) and daily BI dose, the proportion of participants with HbA1c less than 7.0% (< 53 mmol/mol) and FPG less than 7.0 mmol/L and the incidence of hypoglycaemia., Results: Of 421 participants, 124 (29.5%) had baseline residual hyperglycaemia (iGlarLixi, n = 64 [31.7%]; iGlar, n = 60 [29.1%]). At week 30, the residual hyperglycaemia rate decreased to 7.0% with iGlarLixi and increased to 43.3% with iGlar. Among participants with baseline residual hyperglycaemia, a greater proportion achieved both HbA1c and FPG targets at week 30 with iGlarLixi versus iGlar (43.8% vs. 16.7%), and iGlarLixi provided greater reductions in HbA1c (least squares mean [LSM] difference, -0.9% [-9.4 mmol/mol]) and 2-hour PPG (LSM difference, -4.7 mmol/L; both P < .001). Daily BI dose and incidence of hypoglycaemia were similar in the two groups., Conclusions: The findings of this post hoc analysis suggest that iGlarLixi had greater benefits than iGlar in reducing the rate of residual hyperglycaemia over 30 weeks in Chinese people with suboptimally controlled T2D on prior BI-based therapy., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)