RESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) remains a formidable challenge in oncology, with its pathogenesis and progression influenced by myriad factors. Among them, the pervasive organic synthetic compound, bisphenol A (BPA), previously linked with various adverse health effects, has been speculated to play a role. This study endeavors to elucidate the complex interplay between BPA, the immune microenvironment of HCC, and the broader molecular landscape of this malignancy. METHODS: A comprehensive analysis was undertaken using data procured from both The Cancer Genome Atlas and the Comparative Toxicogenomics Database. Rigorous differential expression analyses were executed, supplemented by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. In addition, single-sample gene set enrichment analysis, gene set enrichment analysis and gene set variation analysis were employed to reveal potential molecular links and insights. Immune infiltration patterns were delineated, and a series of in vitro experiments on HCC cells were conducted to directly assess the impact of BPA exposure. RESULTS: Our findings unveiled a diverse array of active immune cells and functions within HCC. Distinct correlations emerged between high-immune-related scores, established markers of the tumor microenvironment and the expression of immune checkpoint genes. A significant discovery was the identification of key genes simultaneously associated with immune-related pathways and BPA exposure. Leveraging these genes, a prognostic model was crafted, offering predictive insights into HCC patient outcomes. Intriguingly, in vitro studies suggested that BPA exposure could promote proliferation in HCC cells. CONCLUSION: This research underscores the multifaceted nature of HCC's immune microenvironment and sheds light on BPA's potential modulatory effects therein. The constructed prognostic model, if validated further, could serve as a robust tool for risk stratification in HCC, potentially guiding therapeutic strategies. Furthermore, the implications of the findings for immunotherapy are profound, suggesting new avenues for enhancing treatment efficacy. As the battle against HCC continues, understanding of environmental modulators like BPA becomes increasingly pivotal.
Assuntos
Compostos Benzidrílicos , Carcinoma Hepatocelular , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Fenóis , Microambiente Tumoral , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Compostos Benzidrílicos/efeitos adversos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Humanos , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Fenóis/efeitos adversos , Fenóis/toxicidade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genéticaRESUMO
Endocrine disruptors are considered estrogenic disruptors, and recent researches suggested that they may have a link to the severity of asthma. We aim to validate the correlation between endocrine disruptors and various clinical measurements of asthma, depending on the menopausal status. A pilot case-control study was performed in female asthmatic patients who visited allergy clinic in SMG-SNU Boramae Medical Center. Medical information and the urinary concentrations of 4 endocrine disruptors on their first visit were collected and analyzed: bisphenol A, mono (2-ethyl-5-hydroxyhexyl) phthalate, mono (2-ethyl-5-oxohexyl) phthalate, and mono-n-butyl phthalate. A total of 35 female participants enrolled in the study, including 20 asthmatic patients and 15 healthy controls. The average concentrations of urinary endocrine disruptors in patient and control group did not demonstrate significant differences. Twenty asthmatic patients were divided into 2 groups according to their menstrual state. Using the Spearman rank correlation test in premenopausal asthmatic patients (nâ =â 7), we found negative correlations between urinary concentration of mono-n-butyl phthalate and asthma control test score, as well as postbronchodilator forced expiratory flow at 25% to 75% of forced vital capacity (P-valueâ =â .007 and .04, respectively). In contrast, it did not show any correlation with asthma control test or postbronchodilator forced expiratory flow at 25% to 75% of forced vital capacity (P-valueâ =â 1.00 and .74, respectively) in postmenopausal group (nâ =â 13). Endocrine disruptors might have an impact on the decline of small airway function and asthma management among premenopausal, but not postmenopausal, female asthmatic patients.
Assuntos
Asma , Compostos Benzidrílicos , Fenóis , Ácidos Ftálicos , Humanos , Feminino , Asma/urina , Asma/tratamento farmacológico , Projetos Piloto , Fenóis/urina , Fenóis/efeitos adversos , Ácidos Ftálicos/urina , Ácidos Ftálicos/efeitos adversos , Compostos Benzidrílicos/urina , Compostos Benzidrílicos/efeitos adversos , Adulto , Estudos de Casos e Controles , Pessoa de Meia-Idade , Disruptores Endócrinos/urina , Disruptores Endócrinos/efeitos adversos , Exposição Ambiental/efeitos adversosAssuntos
Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Doença Aguda , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Glucosídeos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversosRESUMO
INTRODUCTION: According to the Institute of Environmental Sciences, endocrine-disrupting chemicals (EDCs) are "natural or human-made chemicals that may mimic, block, or interfere with the body's hormones, associated with a wide array of health issues", mainly in the endocrine system. Recent studies have discussed the potential contribution of EDCs as risk factors leading to diabetes mellitus type 1 (T1DM), through various cellular and molecular pathways. PURPOSE: The purpose of this study was to investigate the correlation between the EDCs and the development of T1DM. METHODOLOGY: Thus, a 5-year systematic review was conducted to bring light to this research question. Using the meta-analysis and systematic review guideline protocol, a PRISMA flow diagram was constructed and, using the keywords (diabetes mellitus type 1) AND (endocrine-disrupting chemicals) in the databases PubMed, Scopus and ScienceDirect, the relevant data was collected and extracted into tables. Quality assessment tools were employed to evaluate the quality of the content of each article retrieved. RESULTS: Based on the data collected and extracted from both human and animal studies, an association was found between T1DM and certain EDCs, such as bisphenol A (BPA), bisphenol S (BPS), persistent organic pollutants (POPs), phthalates and dioxins. Moreover, based on the quality assessments performed, using the Newcastle-Ottawa Scale and ARRIVE quality assessment tool, the articles were considered of high quality and thus eligible to justify the correlation of the EDCs and the development of T1DM. CONCLUSION: Based on the above study, the correlation can be justified; however, additional studies can be made focusing mainly on humans to understand further the pathophysiologic mechanism involved in this association.
Assuntos
Diabetes Mellitus Tipo 1 , Disruptores Endócrinos , Fenóis , Humanos , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/toxicidade , Diabetes Mellitus Tipo 1/induzido quimicamente , Fenóis/toxicidade , Fenóis/efeitos adversos , Animais , Compostos Benzidrílicos/toxicidade , Compostos Benzidrílicos/efeitos adversos , Poluentes Orgânicos Persistentes/efeitos adversos , Ácidos Ftálicos/toxicidade , Ácidos Ftálicos/efeitos adversos , Exposição Ambiental/efeitos adversos , SulfonasRESUMO
BACKGROUND: Phenylketonuria (PKU) is the most common amino acid metabolism disorder. Patients with blood phenylalanine (Phe) levels of ≥6 mg/dL require treatment, and the most definitive treatment is the Phe-restricted diet. Bisphenols and phthalates are widely used endocrine-disrupting chemicals (EDCs) found in personal care products, baby bottles, and food packaging. METHODS: In this study, we evaluated the possible routes of exposure to these EDCs in patients diagnosed with PKU (n = 105, 2-6 years of age) and determined the relationship between the plasma levels of bisphenol A (BPA), bisphenol F (BPF), di-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), mono-(2ethylhexyl) phthalate (MEHP), and dietary regimens. Participant characteristics and exposure routes were evaluated according to their dietary treatment status. RESULTS: Thirty-four of these patients were on a Phe-restricted diet, while the remaining 71 had no dietary restrictions. DBP and DEHP levels were higher in those using plastic tablecloths (p = 0.049 and p = 0.04, respectively). In addition, plasma DBP levels were higher in those who used bottled water (p = 0.01). Being under 4 years of age, using plastic food containers, and using plastic shower curtains were characteristics associated with higher MEHP levels (p = 0.027, p = 0.019, and p = 0.014, respectively). After adjustment for baseline characteristics (Model 1), the odds of having a plasma BPA level in the upper tertile were 3.34 times higher in the free-diet group (95% CI = 1.09-10.25). When we additionally adjusted for plastic exposure (Model 2), the odds ratio was found to be 18.64 (95% CI = 2.09-166.42) for BPA. In the free-diet group, the probability of having plasma DEHP levels in the upper tertile was increased by a relative risk of 3.01 (p = 0.039, 95% CI = 1.06-8.60). CONCLUSION: Our results indicate that exposure to bisphenols and phthalates varies with dietary treatment. The difference in sources of exposure to EDCs between the diet and non-diet groups indicates that diet plays an important role in EDC exposure.
Assuntos
Compostos Benzidrílicos , Fenóis , Fenilcetonúrias , Ácidos Ftálicos , Humanos , Fenóis/sangue , Fenóis/efeitos adversos , Compostos Benzidrílicos/sangue , Compostos Benzidrílicos/efeitos adversos , Fenilcetonúrias/sangue , Masculino , Feminino , Ácidos Ftálicos/sangue , Ácidos Ftálicos/efeitos adversos , Pré-Escolar , Criança , Disruptores Endócrinos/sangue , Disruptores Endócrinos/efeitos adversos , Embalagem de Alimentos , Dietilexilftalato/sangue , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Dieta , Fenilalanina/sangue , Estado NutricionalRESUMO
INTRODUCTION: Exposure to endocrine disrupting chemicals (EDCs) can result in alterations of natural hormones in the body. The aim of this review article is to highlight the knowledge about EDCs and obesity. METHODS: A scoping review of the electronic literature was performed using PubMed platform for studies on EDCs and obesity published between the years 2013-2023. A total of 10 systematic reviews and meta-analysis studies met our inclusion criteria on more prominent EDCs focusing mainly on bisphenols, including parabens, triclosan, and phthalates, and their association with obesity. DESIGN: Scoping review. RESULTS: EDCs, mostly bisphenols and phthalates, are related to health effects, while there is less information on the impact of parabens and triclosan. A series of negative physiological effects involving obesogenic, diabetogenic, carcinogenic, and inflammatory mechanisms as well as epigenetic and microbiota modulations was related to a prolonged EDCs exposure. A more profound research of particular pollutants is required to illuminate the accelerating effects of particular EDCs, mixtures or their metabolites on the mechanism of the development of obesity. CONCLUSION: Considering the characteristics of EDCs and the heterogeneity of studies, it is necessary to design specific studies of effect tracking and, in particular, education about daily preventive exposure to EDCs for the preservation of long-term public health.
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Disruptores Endócrinos , Obesidade , Ácidos Ftálicos , Humanos , Disruptores Endócrinos/efeitos adversos , Obesidade/prevenção & controle , Ácidos Ftálicos/efeitos adversos , Exposição Ambiental/efeitos adversos , Fenóis/efeitos adversos , Parabenos/efeitos adversos , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/toxicidade , Triclosan/efeitos adversos , Compostos Benzidrílicos/efeitos adversos , FemininoAssuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metformina , Vildagliptina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Metformina/uso terapêutico , Metformina/farmacologia , Vildagliptina/farmacologia , Vildagliptina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Glucosídeos/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/efeitos adversos , Pirrolidinas/uso terapêutico , Pirrolidinas/farmacologia , Pirrolidinas/efeitos adversos , Quimioterapia Combinada/métodos , Nitrilas/uso terapêutico , Nitrilas/efeitos adversos , Adamantano/análogos & derivados , Adamantano/uso terapêutico , Adamantano/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/farmacologiaRESUMO
PURPOSE: We evaluated the pharmacokinetics, safety, and tolerability of a fixed-dose combination (FDC) of dapagliflozin/sitagliptin versus individual component (IC) tablets in healthy Western and Korean participants. The combination of these antihyperglycemic drugs provides efficient glucose control, and the use of FDC has generally been shown to improve medication adherence in individuals with type 2 diabetes mellitus (T2DM). METHODS: Two randomized, open-label, two-period, two-treatment, single-dose, single-center, crossover bioequivalence studies conducted on healthy fasted German participants (aged 18-55 years; Western study) and South Korean participants (aged 19-55 years; Korean study) were included. In both studies, pharmacokinetic parameters (maximum [peak] plasma concentration [Cmax], area under the plasma concentration-time curve from zero to the last quantifiable concentration [AUClast], and area under the plasma concentration-time curve from zero to infinity [AUCinf]) were used to assess the bioequivalence of 10 mg dapagliflozin/100 mg sitagliptin FDC (Treatment A) with their ICs (Treatment B) under fasted conditions. Safety and tolerability were assessed throughout the study. FINDINGS: Forty-six healthy participants (male, 60.9%; mean age, 39.5 years; mean body mass index [BMI], 23.9 kg/m2) were randomized in the Western study, and 51 healthy participants (male, 100.0%; mean age, 24.6 years; mean BMI, 23.9 kg/m2) were randomized in the Korean study. In both studies, the participants were randomized 1:1 into treatment sequence AB and treatment sequence BA. Dapagliflozin/sitagliptin FDC was bioequivalent to IC tablets in both Western and Korean studies, as the 90% confidence interval of the FDC to IC ratios of the geometric least-squares means of the pharmacokinetic parameters for both dapagliflozin and sitagliptin was within the 0.8000-1.2500 bioequivalence criterion limit. The observed differences in pharmacokinetic parameters, such as Cmax, AUClast, and AUCinf, between the Western and Korean studies were not clinically meaningful. Dapagliflozin/sitagliptin FDC and their ICs were well tolerated, with no serious adverse events reported in any of the study populations. IMPLICATIONS: The 10 mg dapagliflozin/100 mg sitagliptin FDC and IC formulations were bioequivalent in fasted healthy Western and Korean participants, with no new safety concerns identified, thus offering a useful alternative for patients currently receiving individual medications as part of their treatment regimen. CLINICAL TRIAL REGISTRATION: Western study (clinicaltrials.gov: NCT05266404) and Korean study (clinicaltrials.gov: NCT05453786).
Assuntos
Compostos Benzidrílicos , Estudos Cross-Over , Combinação de Medicamentos , Glucosídeos , Hipoglicemiantes , Fosfato de Sitagliptina , Humanos , Compostos Benzidrílicos/farmacocinética , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Adulto , Glucosídeos/farmacocinética , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fosfato de Sitagliptina/farmacocinética , Fosfato de Sitagliptina/administração & dosagem , Fosfato de Sitagliptina/efeitos adversos , Feminino , Adulto Jovem , República da Coreia , Adolescente , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Equivalência Terapêutica , Povo Asiático , População Branca , Área Sob a Curva , Alemanha , Voluntários SaudáveisRESUMO
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are extensively used in the management of heart failure because of their cardiovascular benefits. Adverse drug reactions associated with dapagliflozin include diabetic ketoacidosis, fungal infections, and increased blood glucose concentrations. However, abnormal uterine bleeding is not a known side effect of dapagliflozin. We report a 75-year-old Chinese woman with dilated cardiomyopathy and chronic heart failure who experienced abnormal uterine bleeding while taking dapagliflozin. Notably, cessation of dapagliflozin administration resulted in the disappearance of uterine bleeding. These findings suggest that dapagliflozin possesses additional potential mechanisms, but these mechanisms require further investigation. Furthermore, healthcare professionals should remain vigilant regarding the occurrence of uterine bleeding when prescribing dapagliflozin.
Assuntos
Compostos Benzidrílicos , Cardiomiopatia Dilatada , Glucosídeos , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Hemorragia Uterina , Humanos , Feminino , Idoso , Insuficiência Cardíaca/induzido quimicamente , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Cardiomiopatia Dilatada/induzido quimicamente , Hemorragia Uterina/induzido quimicamente , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Doença CrônicaRESUMO
BACKGROUND/ OBJECTIVES: Rosacea is a common chronic inflammatory skin disorder. Endocrinedisrupting chemicals (EDC) are toxic substances, that may gain entry through the skin and subsequently interfere with hormonal and immune functions. Bisphenol A (BPA) and pentachlorophenol sodium (PCS) are two of these EDCs, incriminated in the pathogenesis of certain inflammatory skin disorders. We aimed to test the hypothesis that exposure to BPA and PCS might be involved in the pathogenesis of rosacea. METHODS: This prospective cross-sectional study involved 34 patients with rosacea (18F/16 M; mean age 48.5 ± 11 years) and 34 age and sex-matched healthy controls (20 F/14 M; mean age 48.2 ± 10.2 years). Main anthropometric measures, fasting plasma glucose (FPG), insulin, HOMA-IR, lipids, C-reactive protein (CRP), BPA, and PCS levels were quantified and recorded. RESULTS: Serum CRP (9.6 ± 3.4 vs. 3.7 ± 1.6 mg/L, respectively, p0.05 for all). Serum BPA levels were 55.8 ± 14.4 and 51.9 ± 19.2 ng/mL, and PCS levels were 63.3 ± 45.9 ng/mL and 68.6 ± 40.8 ng/mL for patients and healthy controls, respectively. There was no significant difference in BPA and PCS levels between the two groups (p > 0.05 for both). No significant association was found among HOMAIR, CRP, BPA, and PCS levels (p > 0.05 for all). CONCLUSIONS: Although the present study fails to provide presumptive evidence for the role of BPA and PCS in rosacea, the question as to other EDCs might be involved in its etiopathogenesis remains. This hypothesis requires confirmation in large-scale future prospective trials.
Assuntos
Compostos Benzidrílicos , Pentaclorofenol , Fenóis , Rosácea , Humanos , Compostos Benzidrílicos/sangue , Compostos Benzidrílicos/efeitos adversos , Pessoa de Meia-Idade , Masculino , Feminino , Rosácea/induzido quimicamente , Rosácea/sangue , Pentaclorofenol/sangue , Adulto , Estudos Transversais , Estudos Prospectivos , Disruptores Endócrinos/sangue , Disruptores Endócrinos/efeitos adversos , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , GlicemiaAssuntos
Infarto do Miocárdio , Inibidores do Transportador 2 de Sódio-Glicose , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Humanos , Infarto do Miocárdio/tratamento farmacológico , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/administração & dosagem , Glucosídeos/farmacologia , Glucosídeos/efeitos adversos , Glucosídeos/administração & dosagem , Hipoglicemiantes/farmacologia , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/administração & dosagem , Ensaios Clínicos como AssuntoRESUMO
BACKGROUND: Neurodevelopmental disorders (NDDs) like intellectual disability (ID) are highly heritable, but the environment plays an important role. For example, endocrine disrupting chemicals (EDCs), including bisphenol A (BPA) and its analogues, have been termed neuroendocrine disruptors. This study aimed to evaluate the influence of different genetic polymorphisms (SNPs) on cognitive function in Spanish schoolchildren according to dietary bisphenol exposure. METHODS: A total of 102 children aged 6-12 years old were included. Ten SNPs in genes involved in brain development, synaptic plasticity, and neurotransmission (BDNF, NTRK2, HTR2A, MTHFR, OXTR, SLC6A2, and SNAP25) were genotyped. Then, dietary exposure to bisphenols (BPA plus BPS) was estimated and cognitive functions were assessed using the WISC-V Spanish form. RESULTS: BDNF rs11030101-T and SNAP25 rs363039-A allele carriers scored better on the fluid reasoning domain, except for those inheriting the BDNF rs6265-A allele, who had lower scores. Secondly, relevant SNP-bisphenol interactions existed in verbal comprehension (NTRK2 rs10868235 (p-int = 0.043)), working memory (HTR2A rs7997012 (p-int = 0.002), MTHFR rs1801133 (p-int = 0.026), and OXTR rs53576 (p-int = 0.030)) and fluid reasoning (SLC6A2 rs998424 (p-int = 0.004)). CONCLUSIONS: Our findings provide the first proof that exploring the synergistic or additive effects between genetic variability and bisphenol exposure on cognitive function could lead to a better understanding of the multifactorial and polygenic aetiology of NDDs.
Assuntos
Compostos Benzidrílicos , Fator Neurotrófico Derivado do Encéfalo , Cognição , Disruptores Endócrinos , Fenóis , Polimorfismo de Nucleotídeo Único , Humanos , Criança , Fenóis/efeitos adversos , Compostos Benzidrílicos/efeitos adversos , Feminino , Masculino , Espanha , Cognição/efeitos dos fármacos , Disruptores Endócrinos/efeitos adversos , Fator Neurotrófico Derivado do Encéfalo/genética , Exposição Dietética/efeitos adversos , Receptores de Ocitocina/genética , Proteína 25 Associada a Sinaptossoma/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Receptor 5-HT2A de Serotonina/genética , Receptor trkB/genética , Alelos , Genótipo , Glicoproteínas de MembranaRESUMO
Objective: This study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management. Methods: This study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks. Results: Overall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of -29.3% (95% confidence interval [CI]: -34.8, -23.7), compared to that of -31.8% in the dapagliflozin group (95% CI: -34.8, -23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by -1.30% (95% CI: -1.43, -1.18) in the PEG-Loxe group and by -1.29% (95% CI: -1.42, -1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by -0.56 mmol/L (95% CI: -0.71, -0.42) in the PEG-Loxe group and -0.33 mmol/L (95% CI: -0.48, -0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p > 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group. Conclusions: PEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2300070919.
Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Glucosídeos , Polietilenoglicóis , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Nefropatias Diabéticas/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/administração & dosagem , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Glucosídeos/administração & dosagem , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Idoso , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Resultado do Tratamento , Hemoglobinas Glicadas/análise , Glicemia/efeitos dos fármacos , Glicemia/análise , AdultoRESUMO
BACKGROUND: The efficacy of dapagliflozin in patients with acute heart failure remains unclear. OBJECTIVE: To investigate the impact of dapagliflozin (DAPA) on loop diuretics use and 90-day readmission in patients with acute heart failure. METHODS: In a retrospective cohort study, patients diagnosed with acute heart failure or chronic heart failure with acute exacerbation admitted to Fuyang People's Hospital from January 2021 to April 2023, this study used DAPA (at a dose of 10 mg once daily) in combination with standard treatment. The patients were divided into DAPA group and DAPA-Free group based on whether they used DAPA in acute heart failure. To minimize the influence of confounding factors and ensure comparability between groups, we used propensity score matching (PSM). RESULTS: A total of 399 patients were included, with 206 patients (51.63%) in the DAPA group and 193 patients (48.37%) in the DAPA-Free group. PSM produced 160 pairs. After PSM, there were no statistically significant differences between the DAPA and DAPA-Free groups in terms of readmission of all causes (16.88% vs. 18.12%, OR 0.9141, 95% CI 0.5385-1.552, log rank P = 0.739) or readmission for heart failure (11.88% vs. 15.0%, OR 0.9077, 95% CI 0.4441-1.469, log rank P = 0.484) after 90-day follow-up. Patients in the DAPA group had a lower mean daily dose of intravenous loop diuretics compared to the DAPA-Free group (20 mg/d vs. 30.00 mg/d, P<0.001), lower total loop diuretic dose during hospitalization (106.06 ± 31.23 mg vs. 144.50 ± 45.39 mg, P = 0.038) and a decreased number of diuretic types used (11.88% vs. 23.12%, P = 0.008). CONCLUSIONS: DAPA reduced the dose of intravenous loop diuretics. However, it did not improve all-cause readmission for 90 days or readmission for heart failure after discharge.
Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Readmissão do Paciente , Pontuação de Propensão , Inibidores de Simportadores de Cloreto de Sódio e Potássio , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Estudos Retrospectivos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos , Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem , Doença Aguda , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Glucosídeos/administração & dosagem , Fatores de Tempo , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/administração & dosagem , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Quimioterapia Combinada , China/epidemiologia , Idoso de 80 Anos ou mais , Medição de RiscoRESUMO
Recent scientific results indicate that diet is the primary source of exposure to endocrine-disrupting chemicals (EDCs) due to their use in food processing, pesticides, fertilizers, and migration from packaging to food, particularly in plastic or canned foods. Although EDCs are not listed on nutrition labels, their migration from packaging to food could inadvertently lead to food contamination, affecting individuals by inhalation, ingestion, and direct contact. The aim of our narrative review is to investigate the role of phthalates and bisphenol A (BPA) in foods, assessing their risks for precocious puberty (PP) and early-onset obesity, which are two clinical entities that are often associated and that share common pathogenetic mechanisms. The diverse outcomes observed across different studies highlight the complexity of phthalates and BPA effects on the human body, both in terms of early puberty, particularly in girls, and obesity with its metabolic disruptions. Moreover, obesity, which is independently linked to early puberty, might confound the relationship between exposure to these EDCs and pubertal timing. Given the potential public health implications, it is crucial to adopt a precautionary approach, minimizing exposure to these EDCs, especially in vulnerable populations such as children.
Assuntos
Compostos Benzidrílicos , Disruptores Endócrinos , Contaminação de Alimentos , Fenóis , Ácidos Ftálicos , Puberdade Precoce , Humanos , Puberdade Precoce/induzido quimicamente , Puberdade Precoce/epidemiologia , Fenóis/análise , Fenóis/efeitos adversos , Compostos Benzidrílicos/efeitos adversos , Ácidos Ftálicos/efeitos adversos , Ácidos Ftálicos/análise , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/análise , Contaminação de Alimentos/análise , Criança , Feminino , Obesidade Infantil/epidemiologia , Obesidade Infantil/induzido quimicamente , MasculinoRESUMO
BACKGROUND: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated reduction in heart failure outcomes in patients with type 2 diabetes mellitus, although the exact mechanism of benefit remains unclear. Alteration in left atrial (LA) function due to chronic pressure or volume overload is a hallmark of heart failure. OBJECTIVE: To evaluate the effect of the SGLT2 inhibitor empagliflozin on LA volume and function. METHODS: 90 patients with coronary artery disease and type 2 diabetes (T2DM) were randomized to empagliflozin (n = 44) or placebo (n = 46), and underwent cardiac magnetic resonance (CMR) imaging at baseline and after 6 months. The main outcome was change in LA volume; LA function, including active and passive components, was also measured by a blinded reader. RESULTS: At baseline, there was no significant difference in LA volumes between the empagliflozin (indexed maximum LA volume 26.4 ± 8.4mL/m2, minimum LA volume 11.1 ± 5.7mL/m2) and placebo (indexed maximum LA volume 28.7 ± 8.2mL/m2, minimum LA volume 12.6 ± 5.0mL/m2) groups. After 6 months, changes in LA volumes did not differ with adjusted difference (empagliflozin minus placebo): 0.99 mL/m2 (95% CI: -1.7 to 3.7 mL/m2; p = 0.47) for indexed maximum LA volume, and 0.87 mL/m2 (95% CI: -0.9 to 2.6 mL/m2; p = 0.32) for indexed minimum LA volume. Changes in total LA emptying fraction were also similar, with between-group adjusted mean difference - 0.01 (95% CI: -0.05 to 0.03, p = 0.59). CONCLUSION: SGLT2 inhibition with empagliflozin for 6 months did not have a significant impact on LA volume and function in patients with T2DM and coronary artery disease. (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes [EMPA-HEART]; NCT02998970).
Assuntos
Função do Átrio Esquerdo , Compostos Benzidrílicos , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Masculino , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Idoso , Função do Átrio Esquerdo/efeitos dos fármacos , Resultado do Tratamento , Fatores de Tempo , Método Duplo-Cego , Remodelamento Atrial/efeitos dos fármacos , Átrios do Coração/fisiopatologia , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/diagnóstico por imagemAssuntos
Transtorno Depressivo Maior , Modafinila , Adolescente , Feminino , Humanos , Masculino , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Modafinila/uso terapêutico , Modafinila/farmacologia , Promotores da Vigília/uso terapêuticoAssuntos
Modafinila , Isquemia Miocárdica , Humanos , Modafinila/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Masculino , Eletrocardiografia , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Pessoa de Meia-Idade , Promotores da Vigília/uso terapêutico , Promotores da Vigília/efeitos adversosRESUMO
ABSTRACT: Sodium/glucose cotransporter-2 (SGLT2) inhibitors are a novel class of antidiabetic medications which have proved capable of providing breakthrough cardiovascular (CV) benefits in a variety of clinical scenarios, including patients with heart failure or obesity, irrespective of diabetic status. Several SGLT2 inhibitors are available, but the most prominent ones are canagliflozin, dapagliflozin, and empagliflozin. Several studies have focused on empagliflozin and its effects on the risk of heart failure incidence and recurrences. Most recently, empagliflozin has been recently tested in patients with recent myocardial infarction in the EMPAgliflozin on Hospitalization for Heart Failure and Mortality in Patients With aCuTe Myocardial Infarction randomized trial, with apparently ambiguous findings. The present viewpoint succinctly illustrates the main features of SGLT2 inhibitors as a pharmacologic class, their ever expanding role as a CV medication, and the comparative effectiveness of different individual SGLT2 inhibitors, explicitly commenting on the recent data on empagliflozin in patients with acute myocardial infarction. The reader will find in this article a poignant perspective on this novel avenue for CV prevention and treatment, which greatly expands the management armamentarium of CV practitioners. Indeed, we make the case that SGLT2 inhibitors have a clearly favorable class effect, with differences between individual agents mainly suitable for personalization of care and minimization of side effects.
Assuntos
Compostos Benzidrílicos , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Humanos , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Resultado do Tratamento , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , Medição de Risco , Transportador 2 de Glucose-Sódio/metabolismo , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Animais , Fatores de Risco , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologiaRESUMO
PURPOSE: The purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D) inadequately controlled with metformin and dapagliflozin. METHODS: In this prospective, multicenter, randomized, double-blind, PBO-controlled trial, 366 patients with T2D who did not meet glycemic targets (7.0% ≤ glycosylated hemoglobin [HbA1c] ≤ 10.5%), despite treatment with metformin ≥1000 mg and dapagliflozin 10 mg, received either a PBO, 15 mg of pioglitazone daily (PIO15), or 30 mg of pioglitazone daily (PIO30). The primary end point was the mean change in HbA1c from baseline at 24 weeks across the groups. FINDINGS: For the 366 participants (PBO, n = 124; PIO15, n = 118; PIO30, n = 124), the mean age was 55.6 years and mean duration of diabetes was 8.7 years, with a baseline HbA1c of 7.9%. After 24 weeks, HbA1c reduced significantly in the PIO15 and PIO30 groups from baseline, with intergroup differences of -0.38% and -0.83%, respectively, compared with the PBO group. The proportion of patients with HbA1c levels <7% was significantly higher in the PIO15 and PIO30 groups than in the PBO group. The adverse event rates did not significantly differ across the groups, indicating favorable safety profiles for triple combination therapy using metformin, dapagliflozin, and pioglitazone. IMPLICATIONS: The addition of pioglitazone as a third oral antidiabetic medication is an appropriate option for patients with T2D inadequately controlled with metformin and dapagliflozin based on the resulting significant efficacy in glycemic control and favorable safety profile. CLINICALTRIALS: gov identifier: NCT04885712.