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Diabetic wounds pose a significant challenge in modern healthcare due to their chronic and complex nature, often resulting in delayed healing, infections, and, in severe cases, amputations. In recent years, nanotherapeutic approaches have emerged as promising strategies to address the unique pathophysiological characteristics of diabetic wounds. This review paper provides a comprehensive overview of the latest advancements in nanotherapeutics for diabetic wound treatment. We discuss various nanomaterials and delivery systems employed in these emerging therapies. Furthermore, we explore the integration of biomaterials to enhance the efficacy of nanotherapeutic interventions. By examining the current state-of-the-art research, challenges, and prospects, this review aims to offer valuable insights for researchers, clinicians, and healthcare professionals working in the field of diabetic wound care.
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Cicatrización de Heridas , Humanos , Cicatrización de Heridas/efectos de los fármacos , Nanomedicina , Animales , Sistemas de Liberación de Medicamentos/métodos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Diabetes Mellitus/terapia , Diabetes Mellitus/tratamiento farmacológico , Complicaciones de la Diabetes/terapiaRESUMEN
OBJECTIVE: Diabetes-related care makes up approximately 24% of outpatient clinic visits. Therefore, confidence and understanding of diabetes management is necessary for family medicine residents. METHODS: We developed a combined lecture and simulation lab curriculum utilizing a registered nurse and pharmacist to deliver education to 20 family medicine learners. Pre and post surveys of the educational material were completed in 2 sections including one gauging medical knowledge and a second part gauging level of comfort. RESULTS: Of the learners who participated, fourteen completed the pre-post surveys. Most (53%) respondents improved their scores, while 20% scored the same 27% scored worse. The overall average score increased 57% to 70% and improvement was statistically significant (P < .05). All learners improved confidence by at least 1 point. CONCLUSION: An interprofessional team utilizing a lecture curriculum focusing on providing education on effective prescribing, medication safety profiles, and resource availability, showed improvement in confidence but mixed knowledge benefit. Further modifications to the curriculum may yield further educational gains.
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Curriculum , Diabetes Mellitus , Medicina Familiar y Comunitaria , Internado y Residencia , Humanos , Medicina Familiar y Comunitaria/educación , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/terapia , Relaciones Interprofesionales , Grupo de Atención al Paciente , Competencia Clínica , Administración del Tratamiento Farmacológico/educación , Farmacéuticos , Educación InterprofesionalRESUMEN
BACKGROUND: The coexistence of diabetes and hypertension is prevalent due to shared risk factors. Pharmacological treatment has been reported to be effective in managing both conditions. However, treatment effectiveness depends on the extent to which a patient adheres to their treatment. Poor adherence to long-term treatment for chronic diseases is a growing global problem of significant magnitude. Several interventions have been developed to help improve medication adherence in patients with coexisting diabetes and hypertension. This review aimed to determine the characteristics of these interventions and their impact on medication adherence. METHODS: A systematic review of the literature was conducted using the PRISMA guidelines and registered in the PROSPERO International Registry of Systematic Reviews. Studies were searched in the databases CINAHL, Embase and Medline to identify relevant articles published during 2012-2023. The search concepts included 'medication adherence', 'hypertension', 'diabetes' and 'intervention'. Studies were included if they were in English and evaluated the impact of an intervention aimed at promoting adherence to medications for both diabetes and hypertension. RESULTS: Seven studies met the inclusion criteria, with five demonstrating a statistically significant improvement in medication adherence. Of the five studies that improved medication adherence, four were multifaceted and one was a single-component intervention. All successful interventions addressed at least two factors influencing non-adherence. Patient education was the foundation of most of the successful interventions, supported by other strategies, such as follow-ups and reminders. CONCLUSION: Multifaceted interventions that also included patient education had a positive impact on medication adherence in patients with coexisting diabetes and hypertension. Improving adherence in patients with coexisting diabetes and hypertension requires a multipronged approach that considers the range of factors impacting medication-taking. PATIENT OR PUBLIC CONTRIBUTION: This systematic review provides comprehensive insights into the benefits of patient-centred approaches in intervention development and strengthening. Such patient involvement ensures that medication adherence interventions are more relevant, acceptable and effective, ultimately leading to better health outcomes and more meaningful patient engagement in healthcare research.
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Diabetes Mellitus , Hipertensión , Cumplimiento de la Medicación , Humanos , Hipertensión/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Antihipertensivos/uso terapéuticoRESUMEN
Periodontitis and diabetes mellitus exhibit a bidirectional relationship. This narrative review descriptively outlines the role of chlorhexidine in the periodontal treatment of diabetic patients, focusing on its antimicrobial mechanisms against microbial communities and its antiplaque effects. Although chlorhexidine is proven to be effective in combating microbial presence and improving gingivitis with substantial supporting evidence, its impact on glycemic control and insulin resistance in diabetic patients remains contentious. Additionally, the effectiveness of chlorhexidine as an adjunctive chemotherapeutic in the periodontal treatment of gestational diabetes has not yet been studied, highlighting a gap in research that necessitates further prospective studies and randomized controlled trials. Considering the interconnection between periodontal inflammation and glycemic levels, this article finally advocates for collaborative care between dental and medical professionals to manage periodontitis in diabetic patients effectively.
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Antiinfecciosos Locales , Clorhexidina , Periodontitis , Humanos , Clorhexidina/uso terapéutico , Clorhexidina/administración & dosificación , Periodontitis/tratamiento farmacológico , Periodontitis/complicaciones , Antiinfecciosos Locales/uso terapéutico , Antiinfecciosos Locales/administración & dosificación , Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
This study pooled data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial to estimate the treatment effect of intensive BP on stroke prevention, and investigate whether stroke risk score impacted treatment effect. Of all the potential manifestations of the hypertension, the most severe outcomes were stroke or death. A composite endpoint of time to death or stroke (stroke-free survival [SFS]), whichever occurred first, was defined as the outcome of interest. Participants without prevalent stroke were stratified into stroke risk tertiles based on the predicted revised Framingham Stroke Risk Score. The stratified Cox model was used to calculate the hazard ratio (HR) for the intensive BP treatment. 834 (5.92%) patients had SFS events over a median follow-up of 3.68 years. A reduction in the risk for SFS was observed among the intensive BP group as compared with the standard BP group (HR: 0.76, 95% CI: 0.65, 0.89; risk difference: 0.98([0.20, 1.76]). Further analyses demonstrated the significant benefit of intensive BP treatment on SFS only among participants having a high stroke risk (risk tertile 1: 0.76 [0.52, 1.11], number needed to treat [NNT] = 861; risk tertile 2: 0.87[0.65, 1.16], NNT = 91; risk tertile 3: 0.69[0.56, 0.86], NNT = 50). Intensive BP treatment lowered the risk of SFS, particularly for those at high risk of stroke.
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Antihipertensivos , Presión Sanguínea , Hipertensión , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Persona de Mediana Edad , Hipertensión/tratamiento farmacológico , Hipertensión/complicaciones , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/mortalidad , Factores de Riesgo , Modelos de Riesgos ProporcionalesRESUMEN
The Target-Based Virtual Screening approach is widely employed in drug development, with docking or molecular dynamics techniques commonly utilized for this purpose. This systematic review (SR) aimed to identify in silico therapeutic targets for treating Diabetes mellitus (DM) and answer the question: What therapeutic targets have been used in in silico analyses for the treatment of DM? The SR was developed following the guidelines of the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis, in accordance with the protocol registered in PROSPERO (CRD42022353808). Studies that met the PECo strategy (Problem, Exposure, Context) were included using the following databases: Medline (PubMed), Web of Science, Scopus, Embase, ScienceDirect, and Virtual Health Library. A total of 20 articles were included, which not only identified therapeutic targets in silico but also conducted in vivo analyses to validate the obtained results. The therapeutic targets most frequently indicated in in silico studies were GLUT4, DPP-IV, and PPARγ. In conclusion, a diversity of targets for the treatment of DM was verified through both in silico and in vivo reassessment. This contributes to the discovery of potential new allies for the treatment of DM.
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Simulación por Computador , Diabetes Mellitus , Suplementos Dietéticos , Hipoglucemiantes , Humanos , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Transportador de Glucosa de Tipo 4/metabolismo , Animales , Desarrollo de Medicamentos/métodos , PPAR gamma/metabolismo , Simulación del Acoplamiento Molecular , Terapia Molecular Dirigida/métodosRESUMEN
Diabetes mellitus (DM) is a chronic metabolic disease that predisposes to chronic damage and dysfunction of various organs, including leading to erectile dysfunction (ED) and asthenospermia. Literature suggests that ginseng plays an important role in the treatment and management of DM. Ginseng may have a therapeutic effect on the complications of DM-induced ED and asthenospermia. The study aimed to explore the mechanisms of ginseng in the treatment of DM-induced ED and asthenospermia following the Traditional Chinese Medicine (TCM) theory of "treating different diseases with the same treatment." This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of Ginseng for the treatment of DM-induced ED and asthenospermia. The chemical ingredients and targets of ginseng were acquired using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. The targets of DM, ED, and asthenospermia were extracted with the GeneCards and Online Mendelian Inheritance in Man databases. A protein-protein interaction network analysis was constructed. The Metascape platform was applied for analyzing the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways. AutoDock Vina was used to perform molecular docking. Network pharmacology revealed that the main active components of the target of action were kaempferol, beta-sitosterol, ginsenoside rh2, stigmasterol, and fumarine. Core targets of the protein-protein interaction network included TNF, IL-1ß, AKT1, PTGS2, BCL2, and JUN. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that they were mainly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, Lipid and atherosclerosis. The interactions of core active components and targets were analyzed by molecular docking. Ginseng may play a comprehensive therapeutic role in the treatment of DM-induced ED and asthenospermia through "multicomponent, multi-target, and multi-pathway" biological mechanisms such as inflammation and oxidative stress.
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Astenozoospermia , Disfunción Eréctil , Simulación del Acoplamiento Molecular , Farmacología en Red , Panax , Masculino , Humanos , Panax/química , Disfunción Eréctil/tratamiento farmacológico , Astenozoospermia/tratamiento farmacológico , Medicina Tradicional China/métodos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Mapas de Interacción de Proteínas , Complicaciones de la Diabetes/tratamiento farmacológico , Diabetes Mellitus/tratamiento farmacológico , Sitoesteroles/farmacologíaRESUMEN
Aim: To identify hotspots in this field and provide insights into future research directions. Methods: Publications were retrieved from the Web of Science Core Collection database. R Bibliometrix software, VOSviewer and CiteSpace were used to perform the bibliometric and visualization analyses. Results: The analysis comprised 468 publications from 58 countries, with the United States, China and India being the leading contributors. 'Gene therapy', 'nanoparticles' and 'insulin therapy' are the primary focuses. 'Green synthesis', 'cytotoxicity', 'bioavailability' and 'diabetic foot ulcers' have gained prominence, signifying high-intensity areas of interest expected to persist as favored research topics in the future. Conclusion: This study delves into recent frontiers and topical research directions and provides valuable references for further research in this field.
Diabetes mellitus and its complications are substantial global public health concerns given their elevated mortality rates and economic impact. As an emerging technology of the 21st century, nanotechnology plays a crucial role in the diagnosis, monitoring and treatment of diabetes and its complications, offering advantages such as targeting specificity, excellent biocompatibility and high bioavailability. Bibliometrics can analyze the distribution and correlation of authors/countries/institutions in the published literature of a particular research field. It can also objectively and reliably analyze research hotspots, evolutionary trends and anticipate future developments in a given field. This marks the inaugural bibliometric study delving into the application of nanomedicines in diabetes mellitus and its complications from 2001 to 2023. Our results found that nanotechnology research on diabetes and its complications began in 2001 and is still in a continuous development phase. The United States, China and India being the leading contributors in this field. Zhejiang University has the most research in this area, and ACS Nano is the most popular journal. Zhang Y and Wang X are the most valuable authors. 'Gene therapy', 'nanoparticles' and 'insulin therapy' are the primary focus areas in this field. 'Green synthesis', 'cytotoxicity', 'bioavailability' and 'diabetic foot ulcers' will be the promising interests in the future. This study supplements the research data in this field, offering new perspectives and references for scholars focusing on diabetes and its complications.
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Bibliometría , Diabetes Mellitus , Nanotecnología , Humanos , Diabetes Mellitus/tratamiento farmacológico , Nanotecnología/métodos , Complicaciones de la Diabetes , Nanopartículas , Terapia Genética , Insulina , Nanomedicina/métodos , AnimalesRESUMEN
This study was aimed to evaluate the impact of community pharmacy (CP)-based medication therapy management (MTM) program on clinical and humanistic outcomes in patients with uncontrolled diabetes. An open label, parallel-group randomised controlled trial was undertaken at a community pharmacy in Riyadh city, Kingdom of Saudi Arabia. Patients with a diagnosis of uncontrolled diabetes (HbA1c of ≥ 8%) meeting the eligibility criteria were randomised to receive either the MTM programme provided by pharmacists or standard care. The primary outcome was change in HbA1c over 6 months. Secondary outcomes included: changes in clinical parameters (blood pressure (BP), lipid profile, serum creatinine (SCr) and albumin-to- creatinine ratio (ACR)), types of drug-related problems (DRPs), health service utilization (HSU), adherence, diabetes distress and overall patient satisfaction with the service at 6-month. A sufficiently powered sample of 160 participants with a mean age was 50 years (SD ± 11.9) was recruited. The majority of the patients (68.1%) were male and had diabetes for more than eight years [IQR 3, 14]. After adjusting for baseline HbA1c, compared to the control group, the mean HbA1c level was 0.02% (p = 0.929) and 0.2% (p = 0.47) lower in the intervention arm at 3-month and 6-month respectively. However, these differences were not statistically significant. Nonetheless, within each arm, there was a significant improvement in HbA1c from baseline. Furthermore, the intervention arm demonstrated improvement in BP control (SBP lowered by 3.2 mmHg (p = 0.05) and DBP lowered by 3.8 mmHg (p = 0.008)). During the study period, none of the participants in the intervention group reported hospitalization or ER visits compared to 14 patients in the control group [OR 0.069 (95% CI 0.004, 1.3)]. Patient satisfaction as measured by Patient Satisfaction with Pharmacist Services Questionnaire 2.0 (PSPSQ 2.0) was significantly higher among MTM program participants compared to standard care (p = 0.00001). Patients in the MTM program were eight times more likely to be adherent compared to the patients in the standard care [OR 7.89 (95% CI 3.6, 17.4)]. MTM program metrics showed that per patient, the pharmacists spent a median of 35 [IQR 30, 44.5] minutes at the initial visit and 20 [IQR 10, 25] minutes during the 6-month visit. The number of DRPs had significantly dropped in the intervention arm at 3 and 6-month (p = 0.0001). In conclusion, CP-based MTM program can improve health outcomes and prevent hospitalisations in patients with diabetes. These findings support the implementation of CP-based MTM services for patients with diabetes in the Kingdom of Saudi Arabia.
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Servicios Comunitarios de Farmacia , Hemoglobina Glucada , Administración del Tratamiento Farmacológico , Humanos , Masculino , Femenino , Persona de Mediana Edad , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Arabia Saudita , Adulto , Diabetes Mellitus/tratamiento farmacológico , Satisfacción del Paciente , Farmacéuticos , Resultado del Tratamiento , Hipoglucemiantes/uso terapéutico , Farmacias , Presión Sanguínea/efectos de los fármacosRESUMEN
BACKGROUND: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. METHODS: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. RESULTS: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007). CONCLUSIONS: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02579499.
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Atorvastatina , Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/efectos adversos , Rosuvastatina Cálcica/uso terapéutico , Atorvastatina/efectos adversos , Atorvastatina/uso terapéutico , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Masculino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Femenino , Persona de Mediana Edad , Anciano , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/sangre , Diabetes Mellitus/tratamiento farmacológico , Incidencia , Resultado del Tratamiento , Factores de Riesgo , Factores de Tiempo , Biomarcadores/sangre , Medición de RiesgoRESUMEN
Bioinformatics has expedited the screening of new efficient therapeutic agents for diseases such as diabetes mellitus (DM). The objective of this systematic review (SR) was to understand naturally occurring proteins and peptides studied in silico and subsequently reevaluated in vivo for treating DM, guided by the question: which peptides or proteins have been studied in silico for the treatment of diabetes mellitus? The RS protocol was registered in the International Prospective Register of Systematic Reviews database. Articles meeting the eligibility criteria were selected from the PubMed, ScienceDirect, Scopus, Web of Science, Virtual Health Library (VHL), and EMBASE databases. Five studies that investigated peptides or proteins analyzed in silico and in vivo were selected. Risk of bias assessment was conducted using the adapted Strengthening the Reporting of Empirical Simulation Studies (STRESS) tool. A diverse range of assessed proteins and/or peptides that had a natural origin were investigated in silico and corresponding in vivo reevaluation demonstrated reductions in glycemia and/or insulin, morphological enhancements in pancreatic ß cells, and alterations in the gene expression of markers associated with DM. The in silico studies outlined offer crucial insights into therapeutic strategies for DM, along with promising leads for screening novel therapeutic agents in future trials.
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Simulación por Computador , Diabetes Mellitus , Péptidos , Animales , Humanos , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Biología Computacional/métodos , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Insulina , Péptidos/química , Péptidos/farmacología , Péptidos/uso terapéutico , ProteínasRESUMEN
INTRODUCTION: The management of chronic diabetes mellitus and its complications demands customized glycaemia control strategies. Polypharmacy is prevalent among people with diabetes and comorbidities, which increases the risk of adverse drug reactions. Clinical decision support systems (CDSSs) may constitute an innovative solution to these problems. The aim of our study was to conduct a systematic review assessing the value of CDSSs for the management of antidiabetic drugs (AD). MATERIALS AND METHODS: We systematically searched the scientific literature published between January 2010 and October 2023. The retrieved studies were categorized as non-specific or AD-specific. The studies' quality was assessed using the Mixed Methods Appraisal Tool. The review's results were reported in accordance with the PRISMA guidelines. RESULTS: Twenty studies met our inclusion criteria. The majority of AD-specific studies were conducted more recently (2020-2023) compared to non-specific studies (2010-2015). This trend hints at growing interest in more specialized CDSSs tailored for prescriptions of ADs. The nine AD-specific studies focused on metformin and insulin and demonstrated positive impacts of the CDSSs on different outcomes, including the reduction in the proportion of inappropriate prescriptions of ADs and in hypoglycaemia events. The 11 nonspecific studies showed similar trends for metformin and insulin prescriptions, although the CDSSs' impacts were not significant. There was a predominance of metformin and insulin in the studied CDSSs and a lack of studies on ADs such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. CONCLUSION: The limited number of studies, especially randomized clinical trials, interested in evaluating the application of CDSS in the management of ADs underscores the need for further investigations. Our findings suggest the potential benefit of applying CDSSs to the prescription of ADs particularly in primary care settings and when targeting clinical pharmacists. Finally, establishing core outcome sets is crucial for ensuring consistent and standardized evaluation of these CDSSs.
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Sistemas de Apoyo a Decisiones Clínicas , Hipoglucemiantes , Humanos , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , PolifarmaciaRESUMEN
Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan-Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024-1.692; P < 0.032). Higher dose of rosuvastatin was associated with a higher cumulative incidence of NODM, but this dose-dependency was not apparent with atorvastatin. Cumulative incidence of MACE decreased dose-dependently only with atorvastatin. High-intensity statin was associated with a higher cumulative incidence of NODM in AMI patients, and this association was more evident in rosuvastatin. The different diabetogenic effects of the two statins provide supporting evidence for understanding the nuanced nature of statin treatment in relation to NODM.
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Diabetes Mellitus , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Infarto del Miocardio , Humanos , Infarto del Miocardio/tratamiento farmacológico , Masculino , Femenino , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Persona de Mediana Edad , Anciano , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Rosuvastatina Cálcica/administración & dosificación , Rosuvastatina Cálcica/uso terapéutico , Rosuvastatina Cálcica/efectos adversos , República de Corea/epidemiología , Atorvastatina/administración & dosificación , Atorvastatina/efectos adversos , Atorvastatina/uso terapéutico , Intervención Coronaria Percutánea/efectos adversos , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Sistema de Registros , IncidenciaRESUMEN
Mutations in glucokinase (GCK) can either enhance or inhibit insulin secretion, leading to different forms of diabetes, including gestational diabetes. While many glucokinase activators (GKAs) have been explored as treatments, their long-term effectiveness has often been unsatisfactory. However, recent interest has surged with the introduction of dorzagliatin and TTP399. This study investigates the efficacy of four previously studied compounds (Swertiamarin, Apigenin, Mangiferin, and Tatanan A) in activating GCK using computational methods. Initial molecular docking revealed binding affinities ranging from -6.7 to -8.6 kcal/mol. The compounds were then evaluated for drug-likeness and pharmacokinetic properties. Re-docking studies were performed for validation. Based on their favorable binding affinities and compliance with Lipinski's rule and ADMET criteria, three compounds (Swertiamarin, Apigenin, and Tatanan A) were selected for molecular dynamics (MD) simulations. MD simulations demonstrated that Swertiamarin showed excellent stability, as indicated by analyses of RMSD, RMSF, radius of gyration (Rg), hydrogen bonding, and principal component analysis (PCA). These results suggest that Swertiamarin holds promise for further investigation in in vivo and clinical settings to evaluate its potential in enhancing GCK activity and treating diabetes. This study assessed the potential of four compounds as GCK activators using molecular docking, pharmacokinetic profiling, and MD simulations. Swertiamarin, in particular, showed significant stability and adherence to drug-likeness criteria, making it a promising candidate for further research in combating diabetes.
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Glucoquinasa , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Glucoquinasa/metabolismo , Glucoquinasa/química , Glucoquinasa/genética , Humanos , Medicina Tradicional China , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Enlace de Hidrógeno , Activadores de Enzimas/farmacología , Activadores de Enzimas/química , Simulación por Computador , Apigenina/farmacología , Apigenina/químicaRESUMEN
The integrated stress response (ISR) is a vital signaling pathway initiated by four kinases, PERK, GCN2, HRI and PKR, that ensure cellular resilience and protect cells from challenges. Here, we investigated whether increasing ISR signaling could rescue diabetes-like phenotypes in a mouse model of diet-induced obesity (DIO). We show that the orally available and clinically approved GCN2 activator halofuginone (HF) can activate the ISR in mouse tissues. We found that daily oral administration of HF increases glucose tolerance whilst reducing weight gain, insulin resistance, and serum insulin in DIO mice. Conversely, the ISR inhibitor GSK2656157, used at low doses to optimize its selectivity, aggravates glucose intolerance in DIO mice. Whilst loss of function mutations in mice and humans have revealed that PERK is the essential ISR kinase that protects from diabetes, our work demonstrates the therapeutic value of increasing ISR signaling by activating the related kinase GCN2 to reduce diabetes phenotypes in a DIO mouse model.
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Obesidad , Fenotipo , Piperidinas , Proteínas Serina-Treonina Quinasas , Quinazolinonas , Transducción de Señal , eIF-2 Quinasa , Animales , Quinazolinonas/farmacología , Piperidinas/farmacología , Ratones , eIF-2 Quinasa/metabolismo , eIF-2 Quinasa/genética , Obesidad/patología , Obesidad/metabolismo , Obesidad/prevención & control , Obesidad/genética , Transducción de Señal/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Ratones Endogámicos C57BL , Masculino , Resistencia a la Insulina , Insulina/metabolismo , Insulina/sangre , Estrés Fisiológico/efectos de los fármacos , Modelos Animales de Enfermedad , Dieta Alta en Grasa/efectos adversos , Diabetes Mellitus/patología , Diabetes Mellitus/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/prevención & control , Intolerancia a la Glucosa/tratamiento farmacológico , Adenina/análogos & derivados , IndolesRESUMEN
BACKGROUND: Diabetic Mellitus (DM) has progressively emerged as a worldwide health problem, leading to the widespread deployment of antidiabetic drugs as the primary therapy in the global population. The incidence of diabetes medications-related movement disorders (drMD) is noteworthy but underestimated by clinical practitioners. RESEARCH DESIGN AND METHODS: In order to address the incidence of drMD in DM patients and realize the serious outcomes associated with drMD, we conducted a real-world pharmacovigilance study of 612,043 DM patients using the FDA Adverse Event Reporting System (FAERS) database from January 2004 to September 2023. Reporting Odd Ratio (ROR) was calculated to reflect the risk of drMD. A multivariable logistic regression analysis was employed to adjust crude ROR with the mixed factors including age, sex and various antidiabetic treatments. Afterward, a Mendelian Randomization (MR) study was performed to elucidate the underlying genetic correlation between the genetically proxied targets of antidiabetic drugs and motor disorders. RESULTS: Among 11,729 cases of motor adverse events in DM patients, six categories of drMD were significantly associated with DM medications. Noticeably, metformin was revealed to drastically increase the incidence of parkinsonism (adjusted ROR:3.97; 95 %CI (3.03, 5.19), p = 5.68e-24), bradykinesia (adjusted ROR:1.69; 95 %CI (1.07,2.59), p = 0.02) and irregular hyperkinesia, including chorea, choreoathetosis and athetosis. Insulin/insulin analogues and GLP-1 analogues presented notably higher odds of tremor: the adjusted ROR (aROR) of insulin and GLP-1 analogue is respectively 1.24 (95 %CI (1.15,1.34), p = 2.51e-08) and 1.78 (95 %CI (1.65,1.91), p = 5.64e-54). The combined therapeutic effects of multiple genetic variants of metformin, especially AMP-activated protein kinase (AMPK) were markedly linked to a greater likelihood of developing secondary parkinsonism (OR:10.816, p = 0.049) according to MR analyses. CONCLUSION: The use of antidiabetic medications was significantly related to an increased incidence of movement disorders in DM patients. Moreover, MR analyses provided further genetic evidence for the pharmacovigilance study. This comprehensive investigation might help physicians recognize neurological adverse events associated with antidiabetic treatments and administer effective interventions.
Asunto(s)
Hipoglucemiantes , Trastornos del Movimiento , Farmacovigilancia , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Trastornos del Movimiento/epidemiología , Anciano , Adulto , Incidencia , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Diabetes Mellitus/epidemiología , Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/tratamiento farmacológico , Metformina/efectos adversos , Metformina/uso terapéuticoRESUMEN
AIMS: To evaluate the impact of elexacaftor/tezacaftor/ivacaftor (ETI) therapy on Cystic Fibrosis Related Diabetes (CFRD) glycemic control and insulin treatment in patients with CFRD during clinical practice. METHODS: We carried out a retrospective observational study of 23 adult patients with CFRD who started treatment with ETI. They had, at least, one F508del mutation. Data were collected before ETI initiation and 3, 6, and 12 months after. RESULTS: Glycemic control measured by HbA1c significantly improved by 0.3 % (0.1-0.5) after 3 months of ETI therapy (p = 0.004) and kept this improvement during follow-up (p < 0.001). The proportion of patients needing multiple daily injections of insulin was reduced by 16 % (p = 0.023). Total daily insulin dose dropped by 0.12 (0.05-0.18) UI/kg/day (p < 0.001). Data derived from Flash Continuous Glucose Monitoring (CGM) for patients treated with insulin stayed unchanged after insulin reduction, except for a significant 8 % (0.3-15.6) increase in the Time In Tight Range (TITR) between 70 and 140 mg/dL (p = 0.043). CONCLUSION: ETI therapy impacted CFRD in clinical practice reducing insulin needs and improving glycemic control measured by HbA1c and CGM. The improvements can be observed from the first 3 months of treatment.
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Aminofenoles , Benzodioxoles , Glucemia , Fibrosis Quística , Diabetes Mellitus , Combinación de Medicamentos , Hemoglobina Glucada , Indoles , Quinolonas , Humanos , Fibrosis Quística/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Adulto , Quinolonas/uso terapéutico , Benzodioxoles/uso terapéutico , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Aminofenoles/uso terapéutico , Indoles/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Insulina/uso terapéutico , Quinolinas/uso terapéutico , Pirazoles/uso terapéutico , Control Glucémico , Hipoglucemiantes/uso terapéutico , Piridinas/uso terapéutico , Adulto Joven , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , PirrolidinasAsunto(s)
Quelantes , Terapia por Quelación , Ácido Edético , Infarto del Miocardio , Humanos , Quelantes/uso terapéutico , Terapia por Quelación/métodos , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Ácido Edético/administración & dosificación , Infusiones Intravenosas , Diabetes Mellitus/tratamiento farmacológico , Cadmio , Plomo , Prevención Secundaria/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Importance: In 2013, the Trial to Assess Chelation Therapy (TACT) reported that edetate disodium (EDTA)-based chelation significantly reduced cardiovascular disease (CVD) events by 18% in 1708 patients with a prior myocardial infarction (MI). Objective: To replicate the finding of TACT in individuals with diabetes and previous MI. Design, Setting, and Participants: A 2 × 2 factorial, double-masked, placebo-controlled, multicenter trial at 88 sites in the US and Canada, involving participants who were 50 years or older, had diabetes, and had experienced an MI at least 6 weeks before recruitment compared the effect of EDTA-based chelation vs placebo infusions on CVD events and compared the effect of high doses of oral multivitamins and minerals with oral placebo. This article reports on the chelation vs placebo infusion comparisons. Interventions: Eligible participants were randomly assigned to 40 weekly infusions of an EDTA-based chelation solution or matching placebo and to twice daily oral, high-dose multivitamin and mineral supplements or matching placebo for 60 months. This article addresses the chelation study. Main Outcomes and Measures: The primary end point was the composite of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. Median follow-up was 48 months. Primary comparisons were made from patients who received at least 1 assigned infusion. Results: Of the 959 participants (median age, 67 years [IQR, 60-72 years]; 27% females; 78% White, 10% Black, and 20% Hispanic), 483 received at least 1 chelation infusion and 476 at least 1 placebo infusion. A primary end point event occurred in 172 participants (35.6%) in the chelation group and in 170 (35.7%) in the placebo group (adjusted hazard ratio [HR], 0.93; 95% CI, 0.76-1.16; P = .53). The 5-year primary event cumulative incidence rates were 45.8% for the chelation group and 46.5% for the placebo group. CV death, MI, or stroke events occurred in 89 participants (18.4%) in the chelation group and in 94 (19.7%) in the placebo group (adjusted HR, 0.89; 95% CI, 0.66-1.19). Death from any cause occurred in 84 participants (17.4%) in the chelation group and in 84 (17.6%) in the placebo group (adjusted HR, 0.96; 95% CI, 0.71-1.30). Chelation reduced median blood lead levels from 9.03 µg/L at baseline to 3.46 µg/L at infusion 40 (P < .001). Corresponding levels in the placebo group were 9.3 µg/L and 8.7 µg/L, respectively. Conclusions and Relevance: Despite effectively reducing blood lead levels, EDTA chelation was not effective in reducing cardiovascular events in stable patients with coronary artery disease who have diabetes and a history of MI. Trial Registration: ClinicalTrials.gov Identifier: NCT02733185.