-
Clinical Cardiology Jul 2024Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown encouraging results regarding cardiovascular outcomes mainly in patients with diabetes. In the present study, we compared the efficacy of GLP-1 RAs in cardiovascular events between patients with and without diabetes.
METHODS
After finding eligible studies assessing the impact of GLP-1 RAs on cardiovascular events in patients with and without diabetes using a systematic search, we performed a meta-analysis on randomized-controlled trials (RCTs) comparing cardiovascular outcomes between patients taking GLP-1 RAs and placebo stratified by the presence or absence of diabetes. Relative risk (RR) and its 95% confidence interval (CI) were set as the reporting effect size using the random-effects model.
RESULTS
A total of 24 RCTs (50 033 with GLP-1 RAs and 44 514 with placebo) were included. Patients on GLP-1 RAs had lower risk of major adverse cardiovascular events (MACE) (RR 0.87, 95% CI 0.82-0.93), cardiovascular death (RR 0.88, 95% CI 0.82-0.94), myocardial infarction (MI) (RR 0.87, 95% CI 0.77-0.97), stroke (RR 0.86, 95% CI 0.80-0.92), and hospitalization for heart failure (RR 0.90, 95% CI 0.83-0.98). Both subgroups were shown to be effective in terms of MACE and mortality. Nondiabetic patients had decreased risk of hospitalization for heart failure and MI, whereas the diabetic subgroup had marginally nonsignificant efficacy.
CONCLUSION
The findings of this meta-analysis indicated that patients who are overweight/obese but do not have diabetes have a comparable reduction in the risk of adverse cardiovascular events as those with diabetes. These results need to be confirmed further by large-scale randomized trials in the future.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Randomized Controlled Trials as Topic; Cardiovascular Diseases; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Risk Factors; Risk Assessment; Treatment Outcome; Incretins; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38953365
DOI: 10.1002/clc.24314 -
Drug Design, Development and Therapy 2024The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications... (Review)
Review
PURPOSE
The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications in healthy and diseased populations, to provide recommendations for clinical use.
METHODOLOGY
The PubMed and Embase databases were searched to screen studies associated with the pharmacokinetics of semaglutide. The pharmacokinetic parameters included area under the curve plasma concentrations (AUC), maximal plasma concentration (C), time to C, half-life (t), and clearance. The systematic literature search retrieved 17 articles including data on pharmacokinetic profiles after subcutaneously and oral applications of semaglutide, and at least one of the above pharmacokinetic parameter was reported in all included studies.
RESULTS
Semaglutide has a predictable pharmacokinetic profile with a long t that allows for once-weekly subcutaneous administration. The AUC and C of both oral and subcutaneous semaglutide increased with dose. Food and various dosing conditions including water volume and dosing schedules can affect the oral semaglutide exposure. There are limited drug-drug interactions and no dosing adjustments in patients with upper gastrointestinal disease, renal impairment or hepatic impairment. Body weight may affect semaglutide exposure, but further studies are needed to confirm this.
CONCLUSION
This review encompasses all the pharmacokinetic data for subcutaneous and oral semaglutide in both healthy and diseased participants. The existing pharmacokinetic data can assist in developing and evaluating pharmacokinetic models of semaglutide and will help clinicians predict semaglutide dosages. In addition, it can also help optimize future clinical trials.
Topics: Glucagon-Like Peptides; Humans; Administration, Oral; Injections, Subcutaneous; Hypoglycemic Agents; Drug Interactions
PubMed: 38952487
DOI: 10.2147/DDDT.S470826 -
Journal of Obstetrics and Gynaecology :... Dec 2024The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth.
METHODS
On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software.
RESULTS
A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01).
CONCLUSIONS
The inflammatory biomarkers IL-1β, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.
Topics: Humans; Amniotic Fluid; Female; Pregnancy; Premature Birth; Biomarkers; Interleukin-6; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Inflammation; Matrix Metalloproteinase 9; Interleukin-10
PubMed: 38952221
DOI: 10.1080/01443615.2024.2368764 -
Cardiovascular Diabetology Jul 2024The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine... (Meta-Analysis)
Meta-Analysis Review
The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI - 1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI - 1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.
Topics: Humans; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Adolescent; Child; Network Meta-Analysis; Female; Male; Treatment Outcome; Blood Glucose; Randomized Controlled Trials as Topic; Biomarkers; Bayes Theorem; Hypoglycemic Agents; Glycemic Control; Age Factors; Insulin; Dietary Supplements; Exercise Therapy; Exercise; Child, Preschool
PubMed: 38951907
DOI: 10.1186/s12933-024-02301-3 -
BMC Psychiatry Jul 2024Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis.
METHODS
Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies.
RESULTS
Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis.
CONCLUSIONS
These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.
Topics: Humans; Autism Spectrum Disorder; Leptin; Child; Adipokines; Biomarkers
PubMed: 38951775
DOI: 10.1186/s12888-024-05936-4 -
PeerJ 2024Fibroblast growth factor 21 (FGF21) is a key hormone factor that regulates glucose and lipid homeostasis. Exercise may regulate its effects and affect disease states.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Fibroblast growth factor 21 (FGF21) is a key hormone factor that regulates glucose and lipid homeostasis. Exercise may regulate its effects and affect disease states. Therefore, we sought to determine how exercise affects FGF21 concentrations in adults.
METHODS
The review was registered in the International Prospective Systematic Review (PROSPERO, CRD42023471163). The Cochrane Library, PubMed, and Web of Science databases were searched for studies through July 2023. Studies that assessed the effects of exercise training on FGF21 concentration in adults were included. The random effect model, data with standardized mean difference (SMD), and 95% confidence intervals (CI) were used to evaluate the pooled effect size of exercise training on FGF21. The risk of heterogeneity and bias were evaluated. A total of 12 studies involving 401 participants were included.
RESULTS
The total effect size was 0.3 (95% CI [-0.3-0.89], = 0.33) when comparing participants who exercised to those who were sedentary. However, subgroup analysis indicated that concurrent exercise and a duration ≥10 weeks significantly decreased FGF21 concentrations with an effect size of -0.38 (95% CI [-0.74--0.01], < 0.05) and -0.38 (95% CI [-0.63--0.13], < 0.01), respectively.
CONCLUSION
Concurrent exercise and longer duration may be more efficient way to decrease FGF21 concentrations in adults with metabolic disorder.
Topics: Fibroblast Growth Factors; Humans; Exercise; Adult
PubMed: 38948228
DOI: 10.7717/peerj.17615 -
Physiology & Behavior Jun 2024The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside metabolic regulation. There is a growing... (Review)
Review
INTRODUCTION
The roles of metabolic signals, including Glucagon-like peptide 1 (GLP-1), have been implicated in multiple domains outside metabolic regulation. There is a growing interest in repurposing Glucagon-like peptide 1 receptor agonists (GLP-1RAs) as therapeutics for motivation and reward-related behavioural disturbances. Herein, we aim to systematically review the extant evidence on the potential effects of GLP-1RAs on the reward system.
METHODS
The study followed PRISMA guidelines using databases such as OVID, PubMed, Scopus, and Google Scholar. The search focused on "Reward Behavior" and "Glucagon Like Peptide 1 Receptor Agonists" and was restricted to human studies. Quality assessment achieved by the NIH's Quality Assessment of Controlled Intervention Studies RESULTS: GLP-1RAs consistently reduced energy intake and influenced reward-related behaviour. These agents have been associated with decreased neurocortical activation in response to higher rewards and food cues, particularly high-calorie foods, and lowered caloric intake and hunger levels.
DISCUSSION
GLP-1RAs show promise in addressing reward dysfunction linked to food stimuli, obesity, and T2DM. They normalize insulin resistance, and might also modulate dopaminergic signalling and reduce anhedonia. Their effects on glycemic variability and cravings suggest potential applications in addiction disorders.
PubMed: 38945189
DOI: 10.1016/j.physbeh.2024.114622 -
International Journal of Molecular... Jun 2024A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory... (Review)
Review
A central role for neuroinflammation in epileptogenesis has recently been suggested by several investigations. This systematic review explores the role of inflammatory mediators in epileptogenesis, its association with seizure severity, and its correlation with drug-resistant epilepsy (DRE). The study analysed articles published in JCR journals from 2019 to 2024. The search strategy comprised the MESH, free terms of "Neuroinflammation", and selective searches for the following single biomarkers that had previously been selected from the relevant literature: "High mobility group box 1/HMGB1", "Toll-Like-Receptor 4/TLR-4", "Interleukin-1/IL-1", "Interleukin-6/IL-6", "Transforming growth factor beta/TGF-β", and "Tumour necrosis factor-alpha/TNF-α". These queries were all combined with the MESH terms "Epileptogenesis" and "Epilepsy". We found 243 articles related to epileptogenesis and neuroinflammation, with 356 articles from selective searches by biomarker type. After eliminating duplicates, 324 articles were evaluated, with 272 excluded and 55 evaluated by the authors. A total of 21 articles were included in the qualitative evaluation, including 18 case-control studies, 2 case series, and 1 prospective study. As conclusion, this systematic review provides acceptable support for five biomarkers, including TNF-α and some of its soluble receptors (sTNFr2), HMGB1, TLR-4, CCL2 and IL-33. Certain receptors, cytokines, and chemokines are examples of neuroinflammation-related biomarkers that may be crucial for the early diagnosis of refractory epilepsy or may be connected to the control of epileptic seizures. Their value will be better defined by future studies.
Topics: Humans; Biomarkers; Neuroinflammatory Diseases; HMGB1 Protein; Epilepsy; Cytokines; Toll-Like Receptor 4; Drug Resistant Epilepsy
PubMed: 38928193
DOI: 10.3390/ijms25126488 -
Frontiers in Endocrinology 2024Acromegaly is a rare endocrine disorder caused by hypersecretion of growth hormone (GH) from a pituitary adenoma. Elevated GH levels stimulate excess production of...
UNLABELLED
Acromegaly is a rare endocrine disorder caused by hypersecretion of growth hormone (GH) from a pituitary adenoma. Elevated GH levels stimulate excess production of insulin-like growth factor 1 (IGF-1) which leads to the insidious onset of clinical manifestations. The most common primary central nervous system (CNS) tumors, meningiomas originate from the arachnoid layer of the meninges and are typically benign and slow-growing. Meningiomas are over twice as common in women as in men, with age-adjusted incidence (per 100,000 individuals) of 10.66 and 4.75, respectively. Several reports describe co-occurrence of meningiomas and acromegaly. We aimed to determine whether patients with acromegaly are at elevated risk for meningioma. Investigation of the literature showed that co-occurrence of a pituitary adenoma and a meningioma is a rare phenomenon, and the majority of cases involve GH-secreting adenomas. To the best of our knowledge, a systematic review examining the association between meningiomas and elevated GH levels (due to GH-secreting adenomas in acromegaly or exposure to exogenous GH) has never been conducted. The nature of the observed coexistence between acromegaly and meningioma -whether it reflects causation or mere co-association -is unclear, as is the pathophysiologic etiology.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022376998.
Topics: Humans; Meningioma; Acromegaly; Meningeal Neoplasms; Human Growth Hormone; Risk Factors; Adenoma
PubMed: 38919490
DOI: 10.3389/fendo.2024.1407615 -
The Iowa Orthopaedic Journal 2024Female athletes are at increased risk for anterior cruciate ligament (ACL) injuries. The influence of hormonal variation on female ACL injury risk remains ill-defined....
BACKGROUND
Female athletes are at increased risk for anterior cruciate ligament (ACL) injuries. The influence of hormonal variation on female ACL injury risk remains ill-defined. Recent data suggests that the collagen-degrading menstrual hormone relaxin may cyclically impact female ACL tissue quality. This review aims to identify any correlation between menstrual relaxin peaks and rates of female ACL injury.
METHODS
A systematic review was performed, utilizing the MEDLINE, EMBASE, and CINAHL databases. Included studies had to directly address relaxin/female ACL interactions. The primary outcome variable was relaxin proteolysis of the ACL, at cellular, tissue, joint, and whole-organism levels. The secondary outcome variable was any discussed method of moderating relaxin levels, and the clinical results if available.
RESULTS
AllThe numerous relaxin receptors on female ACLs upregulate local collagenolysis and suppress local collagen production. Peak serum relaxin concentrations (SRC) occur during menstrual cycle days 21-24; a time phase associated with greater risk of ACL injury. Oral contraceptives (OCPs) reduce SRC, with a potential ACLprotective effect.
CONCLUSION
A reasonable correlative and plausible causative relationship exists between peak relaxin levels and increased risk of ACL injury in females, and further investigation is warranted. .
Topics: Humans; Relaxin; Female; Anterior Cruciate Ligament Injuries; Menstrual Cycle; Athletic Injuries; Athletes
PubMed: 38919370
DOI: No ID Found