Changes In Glucose Research Articles

Identification and Functional Analysis of Key microRNAs in the Early Extrauterine Environmental Adaptation of Piglets

Neonatal mammals must rapidly adapt to significant physiological changes during the transition from the intrauterine to extrauterine environments. This adaptation, particularly in the metabolic and respiratory systems, is essential for survival. MicroRNAs (miRNAs) are small noncoding RNAs that regulate various physiological and pathological processes by binding to the 3′ untranslated regions of mRNAs. This study aimed to identify miRNAs involved in the early extrauterine adaptation of neonatal piglets and explore their functions. We performed small RNA sequencing on six tissues (heart, liver, spleen, lung, multifidus muscle, and duodenum) from piglets 24 h before birth (day 113 of gestation) and 6 h after birth. A total of 971 miRNA precursors and 1511 mature miRNAs were identified. Tissue-specific expression analysis revealed 881 tissue-specific miRNAs and 164 differentially expressed miRNAs (DE miRNAs) across the tissues. Functional enrichment analysis showed that these DE miRNAs are significantly enriched in pathways related to early extrauterine adaptation, such as the NFκB, PI3K/AKT, and Hippo pathways. Specifically, miR-22-3p was significantly upregulated in the liver post-birth and may regulate the PI3K/AKT pathway by targeting AKT3, promoting gluconeogenesis, and maintaining glucose homeostasis. Dual-luciferase reporter assays and HepG2 cell experiments confirmed AKT3 as a target of miR-22-3p, which activates the AKT/FoxO1 pathway, enhancing gluconeogenesis and glucose production. Furthermore, changes in blood glucose and liver glycogen levels in newborn piglets further support the role of miR-22-3p in glucose homeostasis. This study highlights the importance of miRNAs, particularly miR-22-3p, in the early extrauterine adaptation of neonatal piglets, offering new insights into the physiological adaptation of neonatal mammals.

Effect of iGlarLixi on continuous glucose monitoring-measured time in range in insulin-naive adults with suboptimally controlled type 2 diabetes.

People with type 2 diabetes (T2D) and glycated haemoglobin (HbA1c) ≥9% may benefit from fixed-ratio combination therapies such as iGlarLixi (insulin glargine 100 U/mL and lixisenatide 33 μg/mL). Use of continuous glucose monitoring (CGM) is recommended, but data are lacking to assess the impact of iGlarLixi in individuals with HbA1c ≥9%. Soli-CGM (NCT05114590) was a 16-week, multicentre, open-label study evaluating the efficacy of once-daily iGlarLixi using blinded CGM-based metrics in insulin-naive adults with HbA1c ≥9%-13% who were receiving ≥2 oral antihyperglycaemic agents (OADs) ± glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The primary outcome was the change from baseline to week 16 in percent time in range (TIR; 70-180 mg/dL). Secondary outcomes included change in mean daily blood glucose (BG), maximum postprandial glucose 4 h post-breakfast (PPG-4 h), and time above range (TAR; >180 mg/dL). On-treatment hypoglycaemia was assessed. The study enrolled 124 participants (mean age, 55.6 years; HbA1c, 10.2%). Sixteen weeks of treatment with iGlarLixi improved TIR (+26.2%), mean BG (-52.5 mg/dL), maximum PPG-4 h (-73.7 mg/dL), and TAR (-28.7%); all p < 0.001. Rates of American Diabetes Association level 1 (BG <70 but ≥54 mg/dL) and level 2 (BG <54 mg/dL) hypoglycaemia were reported as 1.4 and 0.6 events per person-year, respectively. No level 3 events (requiring assistance) were reported. In people with T2D suboptimally controlled on ≥2 OADs ± GLP-1 RAs, 16 weeks of treatment with iGlarLixi significantly improved TIR and reduced TAR without severe hypoglycaemia.

Stress-Induced Hyperglycemia Predicts Poor Outcomes in Primary Intracerebral Hemorrhage Patients

Introduction: The current literature suggests hyperglycemia can predict poor outcomes in patients with primary intracerebral hemorrhage (ICH). Chronic hyperglycemia is seen in patients with pre-existing diabetes (DM); however, acute hyperglycemia in non-diabetic patients is defined as stress-induced hyperglycemia (SIH). This study explored the influence of hyperglycemia on outcomes of primary ICH patients both in the presence and absence of pre-existing DM. Methods: Data regarding admission glucose, pre-existing DM, inpatient mortality, and modified Rankin Scale (mRS) scores at discharge were available for 636 patients admitted to Stony Brook Hospital from January 2011 to December 2022 with a primary diagnosis of ICH. Regression models were used to compare outcomes between patients with admission hyperglycemia and/or pre-existing DM to a control group of normoglycemic and non-diabetic ICH patients. Results: Patients with SIH had higher inpatient mortality rates and worse mRS scores at discharge (p &lt; 0.001). An association with higher mortality and worse mRS scores at discharge was also seen in patients with hyperglycemia secondary to DM, although the strength of this association was weaker when compared to patients with SIH. Conclusion: Our findings suggest that SIH may play a greater role in predicting poor outcomes at discharge rather than a history of poorly controlled DM with chronic hyperglycemia. To develop a more thorough understanding of this topic, prospective studies evaluating the effect of changes in serum glucose during hospital stay on short and long-term outcomes is needed.

Association of bodyweight loss with changes in lipids, blood pressure, and fasting serum glucose following tirzepatide treatment in Japanese participants with type 2 diabetes: Apost hoc analysis of the SURPASS J-mono trial.

In the SURPASS J-mono trial, tirzepatide demonstrated significant improvements in bodyweight and several metabolic parameters in Japanese participants with type 2 diabetes. This post hoc analysis evaluated the potential relationships between weight loss and metabolic improvements in SURPASS J-mono. Metabolic parameter data from tirzepatide-treated participants were analyzed by weight loss subgroups and compared to dulaglutide 0.75 mg. Correlations between changes from baseline to week 52 in weight loss and each metabolic parameter were assessed; Pearson correlation coefficients were derived. Mediation analyses were conducted to evaluate weight loss-associated and -unassociated effects of tirzepatide vs dulaglutide 0.75 mg. This analysis included 548 participants (tirzepatide: n = 411, dulaglutide: n = 137). Weight loss subgroups showed greater improvement in metabolic parameters with greater bodyweight loss. Significant (P < 0.05) but weak correlations between changes in bodyweight and triglycerides (r = 0.18-0.25), high-density lipoprotein cholesterol (r = -0.37 to -0.29), and systolic blood pressure (r = 0.19-0.41) were observed across treatment groups; in diastolic blood pressure in the tirzepatide 5-mg (r = 0.28), pooled tirzepatide (r = 0.20), and dulaglutide 0.75-mg (r = 0.23) groups; and in fasting serum glucose in the dulaglutide 0.75-mg (r = 0.18) and pooled tirzepatide (r = 0.13) groups. Weight loss was associated with treatment differences between tirzepatide and dulaglutide 0.75 mg to varying degrees across metabolic parameters, with improvements in fasting serum glucose having the lowest association with weight loss (36.6%-43.5%). In this post hoc analysis, non-glycemic and glycemic parameter improvements appeared differentially associated with weight loss, suggesting both weight loss-associated and -unassociated effects of tirzepatide.

Effects of Fish Oil with Heat Treatment on Obesity, Inflammation, and Gut Microbiota in Ovariectomized Mice

Background/Objectives: Menopause induces substantial metabolic changes, including a reduction in metabolic rate and an elevated risk of developing metabolic diseases. Fish oil (FO) supplementation has been shown to ameliorate menopause-associated metabolic risks. Hyperthermia treatment (HT) has recently gained attention for its potential to improve metabolic and immune health. However, it remains to be determined whether HT can confer metabolic benefits comparable to those of FO supplementation or enhance the metabolic benefits of FO supplementation. This study aims to delineate the distinctive and collaborative effects of HT and FO supplementation in mitigating menopause-associated metabolic dysfunction. Methods: Female C57BL/6 ovariectomized (OVX) mice were randomly assigned to four groups (n = 12/group) to evaluate the individual and combined effects of FO supplementation (5% w/w) and HT treatment. For HT, whole-body heat exposure was conducted at 40–41 °C for 30 min, 5 days per week. After 12 weeks, animals were used to evaluate the changes in glucose and lipid metabolism, obesity outcome, and inflammatory markers. The gut microbiome analysis was conducted from cecal content by 16S rRNA sequencing. Acute inflammation was induced by lipopolysaccharide (LPS) injection to evaluate inflammatory responses. Results: HT alone distinctively reduced weight gain, lowered core body temperature, and attenuated insulin resistance comparable to FO supplement in OVX mice. The collaborative effect of FO and HT was not evident in metabolic parameters but more prominent in attenuating proinflammatory responses and microbiota modulation. Conclusions: Our findings suggest that the combined treatment of FO supplementation and HT may serve as an effective strategy to mitigate menopause-associated immune susceptibility and metabolic dysfunction. These benefits are likely mediated, at least in part, through the reduction in inflammation and modulation of the gut microbiota.

Change in glucose, insulin and serum lipids due to ultra-processed food consumption in children with obesity.

While the association between ultra-processed food (UPF) consumption and chronic non-communicable diseases in adults is well-established, its relationship with serum markers of chronic diseases in children remains underexplored. This research investigates changes in serum markers in children with obesity during a trial aimed at reducing UPF consumption. The study is a prospective cohort, based on a parallel randomized controlled trial conducted between August 2018 and February 2020, with children aged 7-12 years. Over 6 months, children and their guardians attended monthly consultations and educational activities aimed at reducing UPF consumption. Body weight, height, and 24-h dietary recall were measured at all visits. Serum markers were collected at baseline and at the 2- and 5-month visit (during the intervention). Data from 95 children were analysed. Body mass index (BMI), UPF consumption in grams and energy, and percentage of UPF in grams showed a quadratic trend, initially decreasing, followed by an increase in the following months. Glucose, insulin, and HOMA-IR decreased throughout the study, but after adjustment for BMI, the associations no longer persisted, except for glucose levels, which decreased linearly by 2.25 mg/dL. Reducing UPF consumption may lower blood glucose levels in children with obesity, independent of BMI changes.

An Underlying Mechanism for the Altered Hypoglycemic Effects of Nateglinide in Rats with Acute Peripheral Inflammation

The hypoglycemic effects of nateglinide (NTG) were examined in rats with acute peripheral inflammation (API) induced by carrageenan treatment, and the mechanisms accounting for altered hypoglycemic effects were investigated. NTG was administered through the femoral vein in control and API rats, and its plasma concentration profile was characterized. The time courses of the changes in plasma glucose and insulin levels were also examined. Although the plasma concentration profile of NTG in API rats was marginally distinguishable from that in control rats, the hypoglycemic effect of NTG was more persistent in API rats than in control rats. In addition, NTG elevated the plasma level of insulin more intensely in API rats than in control rats. Then, the islets of Langerhans were procured by perfusing the pancreas with collagenase solution in control and API rats, and the pancreatic mRNA expression of preproinsulin (Ins1), as well as that of sulfonylurea receptor ABCC8 (Abcc8), were examined. As a result, the expression of preproinsulin and ABCC8 mRNA increased in API rats. These findings suggest that the hypoglycemic effect of NTG was potentiated in API rats due to increased insulin secretion in the pancreas, which was caused by enhanced preproinsulin synthesis and expression of the sulfonylurea receptor.

Comparison of GLP-1 Receptor Agonists Combined with Metformin Versus Metformin Alone in the Management of PCOS: A Comprehensive Meta-Analysis.

This study compared the efficacy and safety of glucogan-like peptide-1 receptor agonists (GLP1RAs) combined with metformin versus metformin alone in women with polycystic ovary syndrome (PCOS). A systematic search of "PubMed", "EMBASE", "Cochrane Library", and "Web of Science", "Google Scholar" was conducted up to September 2024. Studies were included if they were RCTs investigating the combination of GLP1RAs and metformin in women diagnosed with PCOS. Eligible studies compared this combination therapy to metformin alone. Primary outcomes included changes in body weight, BMI, waist circumference, fasting glucose, HOMA-IR, androgen levels, and sex hormone-binding globulin (SHBG). Meta-analysis was performed using RevMan 5.4 software. Eight RCTs with a total of 337 participants were included. The combination of GLP1RAs and metformin resulted in significant reductions in body weight (mean difference [MD]=-1.37kg, 95% CI [-2.07, -0.67]; P = 0.0001), BMI (MD= -0.88kg/m², 95% CI [-1.37, -0.39]; P = 0.0005), waist circumference (MD= -2.46cm, 95% CI [-3.59,-1.33]; P < 0.0001), fasting glucose level (MD= -0.30, 95% CI [-0.42,-0.17]; P < 0.0001), and glucose level at 2h after OGTT (MD= -1.58, 95% CI [-2.10,-1.06]; P < 0.0001) compared to metformin alone. Improvements in insulin sensitivity (HOMA-IR) in GLP1RA + Met group were also observed (MD=-1.58, 95% CI [-2.10, -1.06]; P < 0.0001) comparing to Met group. Hormonal outcomes demonstrated an increase in SHBG (MD = 10.04, 95% CI [7.06, 13.01]; P < 0.0001). Adverse events were not different between GLP1RA + Met and Met groups. Collectivley, combination of GLP1RAs and metformin provides superior benefits over metformin alone in reducing body weight, improving insulin sensitivity, and regulating hormonal imbalances in women with PCOS.

Xanomeline-Trospium for Adults with Schizophrenia Experiencing Acute Psychosis: A Systematic Review and Meta-analysis of Safety and Tolerability Outcomes.

The United States Food and Drug Administration approved the xanomeline-trospium combination in September 2024 for treating schizophrenia, based in part on three double-blind, randomized placebo-controlled trials in adults with schizophrenia experiencing acute psychosis. This random-effects model pairwise meta-analysis of those three trials found that xanomeline-trospium was comparable to placebo in terms of all-cause discontinuation, discontinuation rate due to adverse events, Simpson-Angus Scale score change, Barnes Akathisia Rating Scale score change, body weight change, body mass index change, blood pressure change, serum total cholesterol change, blood glucose change, QTc interval changes, and the incidence of headache, somnolence, insomnia, dizziness, akathisia, agitation, tachycardia, gastroesophageal reflux disease, diarrhea, increased weight, and decreased appetite. However, xanomeline-trospium was associated with a higher incidence of at least one adverse event, dry mouth, hypertension, nausea, vomiting, dyspepsia, and constipation, and increased serum triglyceride compared with placebo. Notably, xanomeline-trospium demonstrated superior efficacy than placebo in improving the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive subscale score, and PANSS negative subscale score.

Insights Into Causal Effects of Genetically Proxied Lipids and Lipid-Modifying Drug Targets on Cardiometabolic Diseases.

The differential impact of serum lipids and their targets for lipid modification on cardiometabolic disease risk is debated. This study used Mendelian randomization to investigate the causal relationships and underlying mechanisms. Genetic variants related to lipid profiles and targets for lipid modification were sourced from the Global Lipids Genetics Consortium. Summary data for 10 cardiometabolic diseases were compiled from both discovery and replication data sets. Expression quantitative trait loci data from relevant tissues were employed to evaluate significant lipid-modifying drug targets. Comprehensive analyses including colocalization, mediation, and bioinformatics were conducted to validate the results and investigate potential mediators and mechanisms. Significant causal associations were identified between lipids, lipid-modifying drug targets, and various cardiometabolic diseases. Notably, genetic enhancement of LPL (lipoprotein lipase) was linked to reduced risks of myocardial infarction (odds ratio [OR]1, 0.65 [95% CI, 0.57-0.75], P1=2.60×10-9; OR2, 0.59 [95% CI, 0.49-0.72], P2=1.52×10-7), ischemic heart disease (OR1, 0.968 [95% CI, 0.962-0.975], P1=5.50×10-23; OR2, 0.64 [95% CI, 0.55-0.73], P2=1.72×10-10), and coronary heart disease (OR1, 0.980 [95% CI, 0.975-0.985], P1=3.63×10-14; OR2, 0.64 [95% CI, 0.54-0.75], P2=6.62×10-8) across 2 data sets. Moreover, significant Mendelian randomization and strong colocalization associations for the expression of LPL in blood and subcutaneous adipose tissue were linked with myocardial infarction (OR, 0.918 [95% CI, 0.872-0.967], P=1.24×10-3; PP.H4, 0.99) and coronary heart disease (OR, 0.991 [95% CI, 0.983-0.999], P=0.041; PP.H4=0.92). Glucose levels and blood pressure were identified as mediators in the total effect of LPL on cardiometabolic outcomes. The study substantiates the causal role of lipids in specific cardiometabolic diseases, highlighting LPL as a potent drug target. The effects of LPL are suggested to be influenced by changes in glucose and blood pressure, providing insights into its mechanism of action.

Non-Invasive and Accurate Blood Glucose Detection Based on an Equivalent Bioimpedance Spectrum

Accurate blood glucose monitoring is a key issue for the diagnosis and treatment of diabetes. For this purpose, a non-invasive blood glucose detection method is proposed, which makes use of the equivalent bioelectric impedance spectrum. An impedance detection platform is designed using an automatic balance bridge technique, which can acquire an impedance spectrum within the range of dispersion. Then, the K-nearest neighbor algorithm is used to extract the characteristics of the impedance spectrum. Furthermore, higher-order multiple regression methods are used to establish a blood glucose–electrical impedance spectrum model. Experimental results show that the proposed blood glucose–electrical impedance spectrum model can estimate the change in blood glucose and reliably identify the high blood glucose samples. The correlation between the proposed method and the biochemical blood glucose values can reach 0.89 and 0.87 in personal and multi-person blood glucose tests, respectively. Thus, the proposed method provides a feasible solution for non-invasive blood glucose detection and can help us identify diabetes mellitus.

The influence of high-fat diet on nicotine vapor self-administration, neuronal excitability, and leptin levels in adult mice.

With the rise in fast-food culture and the continued high numbers of tobacco-related deaths, there has been a great deal of interest in understanding the relationship between high-fat diet (HFD) and nicotine use behaviors. Using adult mice and a patch-clamp electrophysiology assay, we investigated the influence of HFD on the excitability of ventral tegmental area (VTA) dopamine neurons and pyramidal neurons in the medial prefrontal cortex (mPFC) given their role in modulating the reinforcing effects of nicotine and natural rewards. We then examined whether HFD-induced changes in peripheral markers were associated with nicotine use behaviors. Here, mice were assigned standard diet (SD) or HFD for 6 weeks and then trained to self-administer nicotine using an e-vape® self-administration (EVSA) assay. After the last session, changes in glucose, insulin, and leptin were assessed with ELISA. HFD-assigned mice displayed a decrease in intrinsic excitability of VTA dopamine neurons; but an increase in intrinsic excitability of layer VI prelimbic mPFC neurons. SD-assigned female mice demonstrated enhanced nicotine EVSA during fixed-ratio 3 relative to SD males. HFD-assigned male and female mice displayed increased nicotine EVSA during FR1. However, only HFD-assigned male mice exhibited enhanced nicotine EVSA during FR3. Finally, HFD-assigned male and female mice displayed increased leptin levels. However, we only observed a direct correlation between leptin levels and EVSA responding during FR1 in HFD-fed male mice. These results suggest that high-fat diet alter nicotine intake in a sex-specific manner, and this may be due to diet-induced changes in neuronal excitability and circulating leptin levels.

The effects of occupational aluminum exposure on blood pressure and blood glucose in workers - A longitudinal study in northern China.

Trace element and metal exposure is closely related to the occurrence of chronic diseases, particularly affecting blood pressure and blood glucose. Current studies suggest that heavy metal exposure is a risk factor for hypertension and diabetes. Aluminum can enter the human body through daily life and occupational exposure from food, environment, drugs, and other sources, affecting the cardiovascular, endocrine, and other systems. Therefore, it is significant to observe the effect of aluminum on blood pressure and blood glucose in workers with high concentration. In this study, electrolytic workers naturally exposed to high concentrations of aluminum were selected. The aim of the 5-year cohort study was to investigate the effects of continuous occupational aluminum exposure on blood pressure and blood glucose in workers and to assess the risk of potential cardiovascular and metabolic diseases due to heavy metal exposure. In 2014, 183 participants from an electrolysis workshop at an aluminum plant in Shanxi were enrolled. Inductively coupled plasma mass spectrometry (ICP-MS) was performed to determine the plasma aluminum (P-Al) concentration of the workers and measured their blood pressure and glucose levels. At the 2019 follow-up, all parameters were measured again in the same workers. The relationship of the P-Al concentration with blood pressure and glucose levels was assessed using generalized linear regression, and risks of developing hypertension and hyperglycemia (diabetes or pre-diabetes) due to Al exposure were assessed using binary logistic regression. Dose-response relationships between average annual rates of change in P-Al and average annual rates of change in blood pressure and blood glucose were analyzed using RCS. The relative risk (RR) and attributable risk (AR) were also calculated. Generalized linear regression showed that the average annual rate of change in P-Al concentration was positively correlated with the annual rates of change in SBP, DBP, and blood glucose levels, with each e-fold increase in P-Al concentration increasing the annual rates of change in SBP and DBP by 3.55 % (P < 0.01) and 3.43 % (P = 0.03), respectively. Binary logistic regression showed that as the average annual rate of change in P-Al concentration (categorical variable) increased, the risk of developing hypertension increased (Ptrend < 0.05). The RCS results showed that the relationship between the average annual rate of change in P-Al and the average annual rate of change in SBP was a showed a dose-response relationship (P for overall association<0.05). RR and AR increased with increasing P-Al concentration in both hypertensive and diabetic patients. Persistent occupational aluminum exposure is associated with elevated blood pressure levels in workers and increases the risk of developing hypertensive disorders.

Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial.

COMBINE 2 assessed the efficacy and safety of once-weekly IcoSema (a combination therapy of basal insulin icodec and semaglutide) vs once-weekly semaglutide (a glucagon-like peptide-1 analogue) 1.0 mg in individuals with type 2 diabetes inadequately managed with GLP-1 receptor agonist (GLP-1 RA) therapy, with or without additional oral glucose-lowering medications. This 52 week, randomised, multicentre, open-label, parallel group, Phase IIIa trial was conducted across 121 sites in 13 countries/regions. Adults with type 2 diabetes (HbA1c 53.0-85.8 mmol/mol [7.0-10.0%]) receiving GLP-1 RA therapy with or without additional oral glucose-lowering medications were randomly assigned 1:1 to once-weekly IcoSema or once-weekly semaglutide 1.0 mg. The primary endpoint was change in HbA1c from baseline to week 52; superiority of IcoSema to semaglutide 1.0 mg was assessed. Secondary endpoints included change in fasting plasma glucose and body weight (baseline to week 52), and combined clinically significant (level 2; <3.0 mmol/l) or severe (level 3; associated with severe cognitive impairment requiring external assistance for recovery) hypoglycaemia (baseline to week 57). Overall, 683 participants were randomised using a Randomisation and Trial Supply Management system to IcoSema (n=342) or semaglutide 1.0 mg (n=341). Mean ± SD baseline characteristics were as follows: HbA1c 64.0±8.2 mmol/mol (8.0±0.7%); diabetes duration 12.6±6.9 years; and BMI 31.1±4.7 kg/m2. From baseline to week 52, mean change in HbA1c was -14.7 mmol/mol (-1.35%-points) in the IcoSema group and -9.88 mmol/mol (-0.90%-points) in the semaglutide group; the estimated treatment difference (ETD) was -4.85 (95% CI -6.13, -3.57) mmol/mol (-0.44 [95% CI -0.56, -0.33]%-points), confirming superiority of IcoSema to semaglutide (p<0.0001). The estimated mean change in fasting plasma glucose from baseline to week 52 was statistically significantly reduced with IcoSema vs semaglutide (-2.48 mmol/l vs -1.43 mmol/l, respectively; ETD -1.05 [95% CI -1.36, -0.75] mmol; p<0.0001). Mean change in body weight from baseline to week 52 was statistically significantly different between groups: +0.84 kg for IcoSema vs -3.70 kg for semaglutide (ETD 4.54 kg [95% CI 3.84, 5.23]; p<0.0001). There was no statistically significant difference in the rate of combined clinically significant or severe hypoglycaemia between IcoSema and semaglutide (0.042 vs 0.036 episodes per person-year of exposure; estimated rate ratio 1.20 [95% CI 0.53, 2.69]; p=0.66). The proportion of participants experiencing gastrointestinal adverse events was similar between treatment groups (IcoSema 31.4%; semaglutide 34.4%). In people living with type 2 diabetes inadequately managed with GLP-1 RA therapy, with or without additional oral glucose-lowering medications, switching to once-weekly IcoSema in comparison with once-weekly semaglutide 1.0 mg demonstrated superiority in HbA1c reduction, similar rates of clinically significant or severe hypoglycaemia, and similar frequency of gastrointestinal adverse events. However, weight change from baseline to week 52 was statistically significantly in favour of semaglutide 1.0 mg. ClinicalTrials.gov NCT05259033 FUNDING: This trial was funded by Novo Nordisk.

Short-term effects of brief stair climbing interruptions on postprandial hyperglycemia during prolonged sitting: a randomized cross-over trial

Prolonged sitting can negatively impact postprandial glucose levels and cognitive function. While short bouts of stair climbing are thought to mitigate these risks, the findings remain inconclusive. The present study aimed to explore the effects of stair climbing bouts on postprandial glucose and cognitive functions during prolonged sitting. Twenty-eight sedentary young adults (aged 20–30 years) underwent two intervention visits after standardised lunch for two hours: (1) STAIR: the participants climbed two flight of stairs for two minutes every 30 min; (2) SIT: the participants continued to sit. Blood glucose was measured using capillary finger prick method while attention function was measured using computer-based cognitive tests at baseline, end of 1st hour and 2nd hour. Significant interaction (F2, 54 = 15.96, p < 0.001) was observed for conditions and time. During STAIR visit, significant changes in postprandial glucose at 1st hour (β = − 2.6 mmol/dl, p < 0.001) and 2nd hour (β = 3.0 mmol/dl, p < 0.001). No significant difference in the attention functions with time and conditions was observed. Stair climbing interruptions may serve as a feasible and effective countermeasure to high glycaemic variability or excursions that occur during prolonged sitting after postprandial hyperglycaemia.

Effectiveness and Safety of Vildagliptin Sustained Release in the Management of Type 2 Diabetes Mellitus: Real-World Evidence in Indian Patients [NOVELTY Study

Vildagliptin sustained release (XR), a formulation that provides vildagliptin 100 mg with a once-daily dose administration, is a recent introduction to manage type 2 diabetes mellitus in India. This study aimed to evaluate the effectiveness and tolerability of vildagliptin XR in patients with type 2 diabetes in real-world clinical settings. This was an observational, prospective, multicenter, cohort study conducted in India, which included patients with type 2 diabetes uncontrolled on metformin XR monotherapy with glycated hemoglobin (HbA1c) >7.00%. Vildagliptin XR was added to their ongoing treatment. The primary endpoint was a change in HbA1c from baseline to 3 months. Secondary endpoints were changes in fasting plasma glucose, postprandial plasma glucose, percentage of patients achieving HbA1c <7.00% at 3 months, and assessment of efficacy, tolerability, and safety. A total of 1691 patients from 118 centers were enrolled in this study, having a mean (standard deviation) age of 53.10 (11) years and a mean (standard deviation) HbA1c of 8.44 (1.35) %. At the end of the study, vildagliptin XR significantly reduced the mean HbA1c by 1.02% points (95% confidence interval 0.93-1.12; p < 0.001) from baseline. The mean fasting plasma glucose and postprandial plasma glucose levels were significantly reduced by 28.44 mg/dL (95% confidence interval 26.64-30.25; p < 0.001) and 48.45 mg/dL (95% confidence interval 45.91-50.99; p < 0.001), respectively, with vildagliptin XR, at the end of study. During the study duration, 34.7% of patients achieved their glycemic target (HbA1c <7.0%) and there were three reported adverse events (all mild in severity). Results demonstrated that vildagliptin XR (100 mg once daily) significantly improved HbA1c and other glycemic parameters in Indian patients with type 2 diabetes and was well tolerated. The study was registered under the Clinical Trials Registry India (CTRI/2022/01/039112).

Exploring metabolic reprogramming in esophageal cancer: the role of key enzymes in glucose, amino acid, and nucleotide pathways and targeted therapies.

Esophageal cancer (EC) is one of the most common malignancies worldwide with the character of poor prognosis and high mortality. Despite significant advancements have been achieved in elucidating the molecular mechanisms of EC, for example, in the discovery of new biomarkers and metabolic pathways, effective treatment options for patients with advanced EC are still limited. Metabolic heterogeneity in EC is a critical factor contributing to poor clinical outcomes. This heterogeneity arises from the complex interplay between the tumor microenvironment and genetic factors of tumor cells, which drives significant metabolic alterations in EC, a process known as metabolic reprogramming. Understanding the mechanisms of metabolic reprogramming is essential for developing new antitumor therapies and improving treatment outcomes. Targeting the distinct metabolic alterations in EC could enable more precise and effective therapies. In this review, we explore the complex metabolic changes in glucose, amino acid, and nucleotide metabolism during the progression of EC, and how these changes drive unique nutritional demands in cancer cells. We also evaluate potential therapies targeting key metabolic enzymes and their clinical applicability. Our work will contribute to enhancing knowledge of metabolic reprogramming in EC and provide new insights and approaches for the clinical treatment of EC.

Beneficial effects of Akkermansia muciniphila on benign prostatic hyperplasia and metabolic syndrome.

Benign prostatic hyperplasia (BPH) is a prevalent condition associated with male lower urinary tract symptoms (LUTS) and is influenced by metabolic syndrome (MetS) and gut microbiota. Akkermansia muciniphila (AKK) is a gut commensal that has emerged as a potential modulator of metabolic health and inflammatory conditions. This study investigated the correlation between Akkermansia abundance and BPH severity and metabolic indices in fecal and serum samples from BPH patients and healthy donors using 16S rRNA sequencing and metabolic profiling. A testosterone-induced BPH mouse model was used to evaluate the effects of AKK administration on BPH severity and metabolic indices. Altered gut microbiota diversity was observed in BPH patients, with a significant reduction in Akkermansia abundance. Akkermansia abundance was negatively correlated with BPH symptom score, serum lipopolysaccharides (LPS), body mass index (BMI), blood glucose, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). AKK administration in BPH mice resulted in histopathological improvements, reduced prostate index, and amelioration of glandular hyperplasia. Although changes in blood glucose, TC, and LDL-C levels post-AKK supplementation were not statistically significant, a trend toward improvement was noted. Additionally, AKK administration led to a reduction in systemic inflammation markers and restoration of intestinal barrier integrity. In conclusion, AKK might modulate the gut microbiota-prostate axis and MetS. AKK's influence on systemic inflammation and gut barrier function suggests its therapeutic promise in managing BPH and associated metabolic disorders. These findings pave the way for novel microbiota-targeted therapies in the treatment of BPH and MetS.

Changes in blood glucose and lipid metabolism levels in children with central precocious puberty and its correlation with obesity.

This study analyzed the changes in blood glucose and lipid metabolism levels in children with central precocious puberty (CPP) and the correlation between CPP and obesity. In total, 88 children with CPP aged 6-10 years who were admitted to our hospital between January 2023 and June 2024 (the CPP group), and 88 children without CPP in the same age group who received health check-ups (the non-CPP group) were retrospectively enrolled in this study. General data [gender, age, bone age, and body mass index (BMI)] were collected. Levels of blood glucose metabolism indicators [fasting plasma glucose (FPG), 2-h postprandial blood glucose (2hPG), and hemoglobin A1c (HbA1c)] and blood lipid metabolism indicators [triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] were compared. The incidence of obesity was calculated, and the Tanner stages of the obese group and the non-obese group were compared. The correlation between CPP degree (measured by Tanner staging) and obesity degree (measured by BMI) was analyzed using Spearman's correlation analysis. The differences in gender and age between the CPP and non-CPP groups were insignificant (P > 0.05). Bone age and BMI in the CPP group were higher than in the non-CPP group (P < 0.05). The CPP group had higher serum FPG, 2hPG, HbA1c, TG, TC, and LDL-C levels and lower serum HDL-C levels than the non-CPP group. The incidence of obesity was higher in the CPP group (21.59%, 19/88) than in the non-CPP group (6.82%, 6/88). The Tanner staging scores in the obese group for the boys (testes and pubic hair), girls (breasts and pubic hair), and as a whole (testes/breasts and pubic hair) were elevated compared to those in the non-obese group (P < 0.05). Spearman's correlation showed that the CPP degree (measured by Tanner staging) was positively correlated with the obesity degree (measured by BMI) in boys, girls, and the study sample as a whole (P < 0.001). Children with CPP had abnormal levels of blood glucose and lipid metabolism, and the CPP degree in these children was positively correlated with the degree of obesity.

Timing of Resistance Exercise and Cardiometabolic Outcomes in Adults with Prediabetes: A Secondary Analysis.

Objective: The objective of this study was to explore if the time of day (AM vs PM) resistance exercise is performed influences glucose and insulin concentrations, body composition, and muscular strength in adults with prediabetes. Methods: A secondary data analysis was conducted using data from the "Resist Diabetes" study, a phase II exercise intervention. Participants (Age:59.9±5.4 yrs; BMI:33±3.7 kg/m2) with prediabetes and overweight or obesity were categorized into AM (N=73) or PM (N=80) exercisers based on when they completed all of their supervised exercise sessions during a 12-week, 2x/week resistance exercise intervention. Blood glucose and insulin derived from oral glucose tolerance tests, body composition, and muscular strength were assessed pre and post resistance exercise training. Inverse propensity score weighting approach was used to estimate the efficacy of AM/PM exercise on the change of clinical responses. Paired samples t-test was used to compare pre-/post outcomes within AM/PM group. Results: No differences between AM and PM exercisers were detected in the change in glucose or insulin areas under the curve (AUC), body composition, or muscular strength. When exploring within-group changes, PM exercisers reduced glucose AUC (change: -800.6 mg/dl*120 min; p=0.01), whereas no significant change was detected for AM exercisers (change: -426.9 mg/dl*120 min; p=0.26). Only AM exercisers increased fat-free mass (change: 0.6 kg; p=0.001). Conclusions: The time of day of resistance exercise is performed may have some impact on glucose concentrations and body composition response. Future randomized clinical trials are needed to understand how exercise timing influences cardiometabolic outcomes in at-risk adults.