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Effect of glucose load on metabolism in patients with type 2 diabetes during elective surgery using remifentanil-induced anesthesia:a randomized controlled trial.
J Med Invest
Asuka Kasai, Kohei Fukuta, Noriko Kambe +3 more
This study aimed to explore the effect of intraoperative glucose load on metabolism in patients with type 2 diabetes anesthetized with remifentanil. A total of 30 patients were enrolled and randomly allocated to one of two groups:no glucose or low-dose glucose (0.1 g/kg/h for 1 hour followed by 0.05 g/kg/h for 1 hour). Glucose, adrenocorticotropic hormone, 3-methylhistidine, insulin, cortisol, free fatty acid, ketone bodies, and creatinine were measured at several points before, during, and after general anesthesia. Glucose levels in the low-dose glucose group increased significantly at 1 and 2 hours after glucose infusion compared to their preanesthetic levels and to those in the no glucose group. Two patients in the low-dose glucose group had blood glucose levels exceeding 11.1 mmol/L. Free fatty acids, ketone bodies, and 3-methylhistidine/creatinine did not differ significantly between groups. Ketone body levels were significantly higher at 1 hour than preanesthetic levels in both groups;after 1 hour, however, they did not change in the no glucose group but significantly decreased in the low-dose glucose group. Intraoperative low-dose glucose load may suppress ketogenesis, but clinicians must consider the risk of causing hyperglycemia in patients with type 2 diabetes undergoing remifentanil-induced anesthesia. J. Med. Invest. 73 : 222-228, February, 2026.
Relative Adrenal Insufficiency is Associated With Worse Clinical Outcomes in Patients With Acute Decompensation of Cirrhosis and Hyponatremia.
J Clin Exp Hepatol
Tanmay Jain, Kalyani Sridharan, Rohit Gupta +4 more
Relative adrenal insufficiency (RAI) and hyponatremia are both common in decompensated cirrhosis. The literature is scarce on the prevalence and clinical correlates of RAI in patients with acute decompensation (AD) of cirrhosis and hyponatremia.
Complete glucocorticoid resistance: a lethal disorder in the neonatal period.
JCEM Case Rep
Natalie Segev, Sarah Swauger, K Nicole Weaver +3 more
Generalized glucocorticoid (GC) resistance (Chrousos syndrome) results from impaired GC receptor signaling due to variants in the NR3C1 gene. Severe neonatal presentations are extremely rare. We report an 8-week-old male infant born at 31-week gestation, with progressive respiratory failure, refractory hypotension, hypokalemic alkalosis, anasarca, jaundice, and multiorgan dysfunction. Laboratory evaluation demonstrated persistently elevated serum cortisol [>60 µg/dL (SI: >1655 nmol/L) (reference range 2.5-9.1 µg/dL, SI: 69.0-251.0 nmol/L)], adrenocorticotropic hormone [>2400 pg/mL (SI: >528 pmol/L) (reference range 7.2-63.3 pg/mL, SI: 1.6-13.9 pmol/L)], aldosterone [2036.0 ng/dL (SI: 56 nmol/L) (reference range 7.0-99.0 ng/dL, SI: 0.2-2.7 nmol/L)], and androgens despite treatment with escalating doses of dexamethasone (up to 12 mg, > 2000 mg/m2/day of hydrocortisone-equivalency). Whole-genome sequencing identified 2 NR3C1 variants: a maternally inherited variant of uncertain significance (c.2181+5 G>C) and a de novo likely pathogenic ∼7.9 kb deletion encompassing exon 8. In silico analyses suggested both variants could disrupt the GC receptor ligand-binding domain, potentially resulting in complete loss of GC receptor function. Autopsy demonstrated adrenomegaly with marked proliferation of zona fasciculata, cholestasis with bile duct paucity, and chronic neonatal lung disease. This case represents a rare and fatal manifestation of complete generalized GC resistance. It highlights the broad physiological role of GC in neonatal homeostasis.
Carnosine Augments the Efficacy of Pulmonary Rehabilitation in COPD: Insights from a Preclinical Model.
Clin Sci (Lond)
Ross Vlahos, Suleman Abdullah Almerdasi, Stanley M H Chan +8 more
Pulmonary rehabilitation (PR) improves exercise tolerance and dyspnoea in chronic obstructive pulmonary disease (COPD) but does not address the elevated cardiovascular disease (CVD) risk. Vascular dysfunction, an early CVD feature, is driven by oxidative stress-a shared pathogenic mechanism in COPD and CVD. Carnosine, a bioactive dipeptide with antioxidant and pH-buffering properties, may enhance muscle performance and protect against vascular injury. This study sought to determine whether carnosine supplementation combined with exercise training could modify early CVD features in a preclinical COPD model. Male BALB/c mice were exposed to room air or cigarette smoke (CS; 9 cigarettes/day, 5 days/week, 8 weeks) with or without carnosine (1 mg/mL in drinking water) and with or without treadmill exercise training (50% maximal speed; 30 min/day, 5 days/week). After 8 weeks, blood pressure, exercise capacity, resting heart rate, lung inflammation, systemic oxidative stress, aortic endothelial function, and platelet activation were assessed. CS impaired weight gain, reduced exercise capacity, elevated resting heart rate, and induced airway inflammation (p<0.0001). CS also caused severe endothelial dysfunction and platelet activation (p<0.0001). Exercise alone did not reverse these vascular abnormalities. In contrast, carnosine plus exercise restored weight gain, exercise capacity, and heart rate, preserved endothelial function, and prevented platelet adhesion and activation, without altering airway inflammation. Exercise training alone is insufficient to counteract CS-induced vascular injury. Carnosine supplementation provides synergistic vascular protection, highlighting its potential as an adjunct to PR to mitigate oxidative stress-driven CVD risk in COPD.
Effect of Once-Daily Macitentan 75 mg on the Pharmacokinetics of Sildenafil, Riociguat, or Rosuvastatin in Healthy Male Participants.
J Clin Pharmacol
Dénes Csonka, Cynthia Gargano, Navin Goyal +3 more
Macitentan is an oral, dual ETA/ETB endothelin receptor antagonist, currently approved in adults for the treatment of pulmonary arterial hypertension (PAH) at a once-daily dose of 10 mg. Pre-clinical and clinical data suggest that greater ETB receptor inhibition may result in greater efficacy. This hypothesis is being tested in the Phase 3 UNISUS study (NCT04273945), comparing once-daily macitentan 75 mg versus macitentan 10 mg. The present Phase 1 study (NCT04211272) evaluated the pharmacokinetics and safety of concomitant administration of once-daily macitentan 75 mg at steady state with substrates of either breast cancer resistance protein (BCRP) transporter (e.g., riociguat and rosuvastatin) or cytochrome P450 3A4 (CYP3A4) enzymes (e.g., sildenafil and tadalafil) in healthy male adults. Macitentan was administered once daily at 10 mg on Days 1 and 2, 37.5 mg on Days 3-5, and 75 mg on Days 6-13. Participants received a single oral dose of sildenafil (20 mg) on Days -4 and 13, riociguat (1 mg) on Days -3 and 10, or rosuvastatin (10 mg) on Days -4 and 10. Geometric mean ratios for the maximum concentration and area under the curve of the substrate and 90% confidence intervals showed no clinically relevant effects on exposure for sildenafil, riociguat, or rosuvastatin when administered alone or with macitentan 75 mg. Co-administration of macitentan and the substrates was generally well tolerated. Due to the lack of clinically relevant drug-drug pharmacokinetic interactions, no dose adjustment is deemed necessary when co-administering once-daily macitentan 75 mg with BCRP or CYP3A4 substrates.
Peptidomimetic Long-Acting Growth Hormone-Releasing Hormone Agonists Promote Tissue Perfusion in Hindlimb Ischemia.
J Med Chem
Haodong Shao, Yuling Wu, Mengyu Mao +9 more
Growth hormone-releasing hormone (GHRH) has shown therapeutic potential in the treatment of various diseases. However, the clinical translation of GHRH receptor (GHRH-R) agonists has been hampered by the short half-life and suboptimal activity. Herein, we report a series of hybrid GHRH analogs developed using sulfono-γ-AA peptide-based peptidomimetic optimization. These hybrid peptides exhibit significantly enhanced potency in activating GHRH-R and stimulating growth hormone release while demonstrating markedly improved serum stability (T1/2 > 24 h). Subcutaneous administration of selected peptides in mice with ischemic hindlimb enhanced blood perfusion and preservation of limb function. They also promoted endothelial regeneration and collateral vessel formation, enhancing vascular remodeling and tissue repair. In vitro, the peptides enhanced the angiogenic potential of endothelial cells, primarily through activation of the ERK signaling pathway. Our findings lay a strong foundation for the development of long-acting GHRH-R agonists with promising therapeutic potential for the treatment of vascular and regenerative disease.
Is There a Causal Link Between GLP-1 Receptor Agonists and Non-Arteritic Anterior Ischaemic Optic Neuropathy? A Critique of the Clinical Evidence.
Clin Exp Ophthalmol
Helen V Danesh-Meyer, Joseph F Rizzo
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for managing Type 2 diabetes and obesity, with well-documented and significant cardiometabolic benefits. Recent observational reports and pharmacovigilance data have raised concerns about a possible association between GLP-1RAs-particularly semaglutide- and non-arteritic anterior ischaemic optic neuropathy (NAION), a rare cause of sudden vision loss. While case reports and spontaneous reporting systems suggest a potential signal, these sources are subject to confounding and reporting bias. Observational studies offer mixed findings, with some Scandinavian registry studies reporting elevated risks while large electronic health record EHR) analyses from the U.S. and multi-national databases have reported null or weak associations. Meta-analyses of randomised controlled trials- the gold standard for causal inference- currently lack power to reliably assess this rare outcome but suggest, at most, a comparatively moderate increase in risk (e.g., odds ratio of 2-3). Overall while a causal link cannot be excluded, the numerous studies that assert an 'association' between GLP-1 RA exposure and NAION should motivate larger pooled analyses of RCTs with adjudicated ocular outcome to definitely assess risk.
LEAN mass Preservation with Resistance Exercise and Protein during semaglutide and tirzepatide therapy (LEAN-PREP study): a protocol for a randomised controlled trial.
BMJ Open
Ameenah A Alawadhi, Dherar Alroudhan, Dalal J Alsaeed +6 more
Obesity is a global public health issue, with its effects a particular issue in Kuwait. Advances in pharmaceutical treatment (eg, glucagon-like peptide-1s) offer an effective solution, with the magnitude of weight lost something to celebrate. However, this level of weight loss also results in dramatic reductions in lean mass, reflecting loss of muscle mass and muscle strength which can predispose people to sarcopenia. This is a particular issue in people with type 2 diabetes in Kuwait, where the prevalence of muscle weakness is extremely high. Solutions to mitigate this loss of muscle mass and strength are needed, with a pragmatic resistance exercise intervention and increasing dietary protein intake having potential. This trial aims to determine whether resistance exercise and/or protein intake can preserve muscle mass and improve physical function in people with obesity initiating semaglutide/tirzepatide therapy.
Combined antiretroviral therapy with low- or normal-protein, high-calorie diets appears to induce significant deleterious electrocardiographic changes in a rodent model.
Braz J Med Biol Res
B M Chege, P W Mwangi, C G Githinji +1 more
The introduction of combination antiretroviral therapy (cART) has significantly reduced AIDS-related morbidity and mortality. However, the prevalence of age-associated comorbidities, particularly cardiovascular diseases (CVD), has increased, becoming a leading cause of mortality in people living with HIV. This study investigated the interaction between cART regimens and dietary composition on electrocardiographic (ECG) parameters and myocardial histopathology. A total of 120 weanling Sprague Dawley rats were allocated to one of three diets for 15 weeks: normal chow, a calorie-dense low protein (CDLP) diet, or a calorie-dense normal protein (CDNP) diet. Each dietary group was then subdivided into four treatment groups for a further 9 weeks: a standard group (normal saline), Test group 1 (dolutegravir (DTG) plus tesamorelin), Test group 2 (DTG only), and a positive control (classical cART regimen). ECG recordings and histological assessments were performed at week 24. Significant intergroup variations in ECG indices were observed, including Q, R, S, and T wave amplitudes, PR interval, QRS duration, ST height, and QTc (all P<0.0001). Myocardial fibrosis (P<0.0001) was evident in animals from the TG2 (DTG only) and PC (classical regimen) groups maintained on CDLP and CDNP diets. These findings demonstrated that CDLP and CDNP diets, combined with DTG-based or classical cART regimens, exerted deleterious cardiac effects, promoting myocardial fibrosis that disrupts normal electrical conduction and may predispose to arrhythmogenesis. Tesamorelin prevented these effects, implicating growth hormone pathway dysfunction in the underlying pathology.
Semaglutide-Associated Acute Pancreatitis in a Patient With Type 2 Diabetes Mellitus: A Case Report.
Cureus
Piyush Puri, Michael Akhavan, Jonathan Shadan +2 more
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist widely prescribed for type 2 diabetes mellitus and obesity, is generally well tolerated but can be associated with gastrointestinal adverse effects and, rarely, pancreatitis. As its use grows, clinicians must remain aware of potential complications, particularly in patients with additional risk factors. We report the case of a 57-year-old woman with diabetes, hypertension, and hyperlipidemia who presented with acute severe epigastric pain and persistent vomiting shortly after consuming a large, fatty meal. She had been receiving semaglutide for several months. Laboratory studies showed marked leukocytosis, hyperglycemia with an anion gap metabolic acidosis, and a lipase level exceeding 3000 U/L. CT imaging demonstrated acute interstitial edematous pancreatitis with peripancreatic fluid and early concern for necrosis. She was treated conservatively with aggressive intravenous hydration, bowel rest, electrolyte repletion, and analgesia. Her condition improved with supportive care, and she was discharged with close outpatient follow-up. This case highlights the importance of recognizing pancreatitis as a possible multifactorial complication in patients using GLP-1 receptor agonists. This case highlights the need for clinicians to maintain awareness of pancreatitis as a potential adverse effect in patients receiving semaglutide, especially those with additional risk factors such as biliary pathology or dietary triggers. As the use of GLP-1 receptor agonists continues to grow, careful assessment of abdominal symptoms and early recognition of pancreatic inflammation are essential for optimizing outcomes and guiding safe prescribing practices.
Clinical outcomes of glucagon-like peptide-1 receptor agonist therapy in kidney transplant recipients: a systematic review and meta-analysis.
Clin Kidney J
Mehmet Kanbay, Sama Mahmoud Abdel-Rahman, Mustafa Guldan +5 more
Metabolic complications after kidney transplantation (KT) significantly affect graft and patient survival. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardio-renal benefits in the general population, but evidence in KT recipients remains limited.
Non-invasive MRI of choroid plexus vascular function.
Imaging Neurosci (Camb)
Peiying Liu, Lori Donaldson, Beini Hu +2 more
Choroid plexus (ChP) is a highly vascularized tissue in the ventricles of the brain, and it plays an important role in the production of cerebrospinal fluid (CSF) and formation of the blood-CSF barrier. The function of ChP vessels has been implicated in waste clearance efficiency during aging and neurodegenerative diseases. At present, postmortem studies are the main method to assess choroid plexus vascular integrity, with a few tools to measure ChP function in living humans. Here, we proposed a non-invasive MRI approach to assess ChP vascular elasticity based on the detection of MRI signal changes in response to vasoactive challenges. The mechanism of the signal is hypothesized to be due to reciprocal blood and stroma volume alterations during vessel expansion. We demonstrated that ChP vascular elasticity can be evaluated with BOLD MRI using a hypercapnia challenge of CO2 inhalation. This effect is specifically located in the brain ventricles where ChP is abundant. We revealed the ability of the technique in detecting age-related reduction in ChP vascular elasticity. We further showed that this effect can be assessed with gas-free methods, including intermittent breath modulation and resting-state BOLD fMRI. We characterized the image contrast requirement under which this effect can be detected. This technique may provide a clinically feasible tool for assessing ChP vascular function in health and disease.
A profile of heart failure in the James and Hudson's Bay region of Ontario: A retrospective cohort study.
Can J Public Health
Sabastian M B Koprich, Samuel J Petrie, Robert P Gagnon +5 more
The James and Hudson Bay (JHB) region in Northern Ontario is home to an estimated 12,000 people; the majority are Mushkegowuk Cree. To better respond to cardiovascular needs in the region and leverage existing partnerships between the Weeneebayko Area Health Authority's Minomathowin Department, ICES, and University Health Network, this study aimed to profile confirmed and possible heart failure (HF) prevalence among community members.
[Clinical and genetic characteristics of 165 children with salt-wasting 21-hydroxylase deficiency in Henan Province].
Zhongguo Dang Dai Er Ke Za Zhi
Hai-Hua Yang, Ai Huang, Yuan Li +2 more
To explore the clinical and genetic characteristics of children with salt-wasting (SW) 21-hydroxylase deficiency (21-OHD) in Henan Province.
Fetal gastric maturation in a rat model: gestational changes in glucose transporter-1, glucose transporter-4, and insulin-like growth factor-1 receptor expression.
Am J Vet Res
Pelin Coştur Filiz, Emin Türkay Korgun
To investigate the relationship between histological maturation of the fetal rat stomach and gestational stage-dependent expression patterns of glucose transporter (GLUT)-1, GLUT-4, and IGF-1 receptor (IGF-1R).
HuR-mediated regulation of mTOR mRNA stability promotes the commitment of satellite cells towards myogenesis.
Cell Death Dis
Anne-Marie K Tremblay, Brenda Janice Sánchez, Bianca Colalillo +6 more
The RNA-binding protein HuR has been shown to promote the differentiation of cultured muscle cells into muscle fibers. HuR mediates this process by differentially regulating, at different stages of this process, mRNA targets encoding pro-myogenic factors. Despite these advancements, the role of HuR, in vivo, at various stages of the myogenic process and its impact on muscle formation and function remain elusive. Towards this end, we used the Myf5-Cre loxP system to knock out HuR at a stage where muscle precursor cells (satellite cells, SCs) commit to myogenesis. Using these mice, we found that the muscle-specific depletion of HuR impairs, physiologically, its formation during embryogenesis and in response to injury. These mice exhibited smaller skeletal muscles and reduced exercise endurance. We demonstrate, using these mice, that this effect is due, in part, to the HuR-mediated regulation of mTOR (mechanistic target of rapamycin) mRNA expression. Using primary and cultured muscle cells, we show that HuR associates with this message, regulating its stability. In doing so, HuR facilitates the commitment of satellite cells toward myogenesis, thus preventing their transdifferentiation toward adipogenesis. These findings thus identify HuR as a master regulator of SCs' commitment to myogenesis and uncover a potential target for manipulating muscle myogenic capacity in both normal and pathological conditions.
Cost-Effectiveness of Incretin Therapies: A Canadian Lens on Diabetes, Obesity, and Emerging Indications.
Can J Physiol Pharmacol
Luke Awadalla, Siena Iskander, Cherry Chu +1 more
Incretin therapies have emerged as key interventions for glycemic control and weight reduction, and are now among Canada's costliest outpatient drug classes. This review synthesizes current clinical and economic evidence on the cost-effectiveness of incretin-based therapies, specifically glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual agonists (e.g., semaglutide, tirzepatide) in patients with type 2 diabetes mellitus (T2DM) or for weight loss. We review data from clinical trials and recent Canadian and international economic models, identify emerging indications, and discuss limitations in current health-technology assessment (HTA) frameworks. Implications for Canadian reimbursement are highlighted, with attention to price, patient selection, and outcome considerations.
GLP-1 Receptor Agonist Use and Wound Outcomes After Free Flap Breast Reconstruction.
J Reconstr Microsurg
Joy Ha, Ethan Lester, Henning De May +4 more
Background Glucagon-like peptide-1 receptor agonists (GLP-1s) are increasingly used for glycemic control and weight loss, but their impact on surgical wound complications remains unclear. Some studies suggest GLP-1s reduce complications such as infection and dehiscence, though others report increased risk in certain procedures. This study evaluates whether preoperative GLP-1 use is associated with postoperative wound complications in free flap breast reconstruction. Methods We conducted a retrospective cohort study using the TriNetX Research Network, a global database of de-identified health records. Adults (≥18 years) undergoing free flap breast reconstruction (2012-2025) were identified with CPT codes. Patients were stratified into cohorts by GLP-1 use within one year before surgery. Prescriptions for semaglutide, liraglutide, dulaglutide, exenatide, or tirzepatide defined GLP-1 users. Cohorts underwent 1:1 propensity score matching, and matched groups were analyzed for wound outcomes. Subgroup analyses were performed by diabetes status. Results In the pooled cohort, GLP-1 users had significantly lower composite wound complication rates compared with non-users (9.0% vs. 17.1%, p = 0.002), including reduced surgical site infections (4.1% vs. 8.1%, p = 0.026) and wound dehiscence (3.8% vs. 7.8%, p = 0.023). No differences were observed in debridement, seroma, or hematoma rates. In subgroup analyses, GLP-1 use was associated with significantly lower composite wound complications in the non-diabetic subgroup (7.9 vs. 18.6%, p = 0.007), while overall complication rates in the diabetic subgroup were comparable between users and non-users. Conclusion Preoperative GLP-1 use was not linked to increased wound complications and may confer benefit, supporting safety when used perioperatively.
The effects of GLP-1 receptor agonists on Alzheimer's pathophysiology: A systematic review.
Mol Cell Neurosci
Eve Corcoran, Michael Kettlety, Urwa Mogul +2 more
The incidence of Alzheimer's disease (AD) is increasing globally but there are limited effective therapies available. Recently, evidence has demonstrated a role of GLP-1 receptor (GLP-1R) agonists, commonly used in the treatment of type 2 diabetes, may have therapeutic potential in AD. GLP-1R agonists have exhibited their neuroprotective role by targeting tau hyperphosphorylation and the accumulation of beta-amyloid (Aβ) plaques. This systematic review aims to evaluate the effectiveness of liraglutide, semaglutide, exenatide and dulaglutide on AD pathology with a focus on the key biomarkers: hyperphosphorylated tau and Aβ.
Spermidine alleviates sepsis-induced cardiomyopathy by improving mitochondrial quality and quantity via a Metallothionein 1-dependent antioxidant pathway.
Phytomedicine
Shiyun Long, Jiaxin Sun, Yaguang Wu +7 more
Sepsis-induced cardiomyopathy (SICM) is characterized by mitochondrial dysfunction, impaired mitophagic flux, and overwhelming oxidative stress. Spermidine (SPD), a natural polyamine known to enhance autophagy and preserve cardiac function in aging and metabolic disorders, has not been systematically evaluated in the context of septic cardiomyopathy.