RESUMO
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
BACKGROUND: The effect of empagliflozin, a sodium-glucose-co-transporter-2 inhibitor, on risk for myocardial infarction has not been fully characterized. METHODS: This study comprised prespecified and post-hoc analyses of the EMPA-REG OUTCOME trial in which 7020 people with type 2 diabetes (T2D) and cardiovascular disease [mostly atherosclerotic (ASCVD)] were randomized to empagliflozin or placebo and followed for a median 3.1 years. We assessed the effect of empagliflozin on total (first plus recurrent) events of centrally adjudicated fatal and non-fatal myocardial infarction (MI) using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post hoc, we analyzed types of MI: type 1 (related to plaque-rupture/thrombus), type 2 (myocardial supply-demand imbalance), type 3 (sudden-death related, i.e. fatal MI), type 4 (percutaneous coronary intervention-related), and type 5 (coronary artery bypass graft-related). MIs could be assigned to > 1 type. RESULTS: There were 421 total MIs (including recurrent); 299, 86, 26, 19, and 1 were classified as type 1, 2, 3, 4, and 5 events, respectively. Overall, empagliflozin reduced the risk of total MI events by 21% [rate ratio for empagliflozin vs. placebo, 0.79 (95% CI, 0.620-0.998), P = 0.0486], largely driven by its effect on type 1 [rate ratio, 0.79 (95% CI, 0.61-1.04)] and type 2 MIs [rate ratio, 0.67 (95% CI, 0.41-1.10)]. CONCLUSIONS: In T2D patients with ASCVD, empagliflozin reduced the risk of MIs, with consistent effects across the two most common etiologies, i.e. type 1 and 2. TRAIL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT01131676.
Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Glucosídeos , Infarto do Miocárdio , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Masculino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/complicações , Resultado do Tratamento , Feminino , Pessoa de Meia-Idade , Idoso , Fatores de Tempo , Medição de Risco , Fatores de Risco , RecidivaRESUMO
BACKGROUND: The connection between urinary bisphenol A (BPA) and hyperlipidemia is still unclear, and few studies have evaluated whether urinary BPA affects mortality among individuals with hyperlipidemia. Therefore, we aimed to investigate the link between urinary BPA and hyperlipidemia and assess the impact of urinary BPA on mortality risk in subjects with hyperlipidemia. METHODS: We analyzed data of the National Health and Nutrition Examination Survey from 2003 to 2016. Multivariable logistic analysis was performed to examine the relationship between urinary BPA and hyperlipidemia. Cox regression analysis was carried out to investigate the relationship between urinary BPA and all-cause mortality in subjects with hyperlipidemia. RESULTS: This study included 8,983 participants, of whom 6,317 (70.3%) were diagnosed with hyperlipidemia. The results showed that urinary BPA was higher in participants with hyperlipidemia group than those without hyperlipidemia (3.87 ± 0.32 vs. 2.98 ± 0.14, P = 0.01). Urinary BPA levels were analyzed in tertiles. Compared with tertile 1 of BPA (reference), the odds ratio (95% confidence interval) of hyperlipidemia related to tertile 3 of BPA was 1.28 (1.11-1.48). The hazard ratio for all-cause death associated with the highest versus lowest tertile of urinary BPA was 1.20 (95% confidence interval: 1.01-1.44; P = 0.04) among participants with hyperlipidemia. CONCLUSIONS: The study indicated a positive relationship between urinary BPA and the risk of hyperlipidemia. Urinary BPA was associated with a significantly higher risk of all-cause mortality in adults with hyperlipidemia.
Assuntos
Compostos Benzidrílicos , Hiperlipidemias , Inquéritos Nutricionais , Fenóis , Humanos , Fenóis/urina , Compostos Benzidrílicos/urina , Compostos Benzidrílicos/efeitos adversos , Hiperlipidemias/urina , Hiperlipidemias/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , IdosoAssuntos
Compostos Benzidrílicos , Microbioma Gastrointestinal , Obesidade Infantil , Fenóis , Humanos , Compostos Benzidrílicos/efeitos adversos , Fenóis/efeitos adversos , Fenóis/toxicidade , Obesidade Infantil/microbiologia , Obesidade Infantil/epidemiologia , Criança , Microbioma Gastrointestinal/efeitos dos fármacos , Feminino , Masculino , Exposição Ambiental/efeitos adversosAssuntos
Compostos Benzidrílicos , Microbioma Gastrointestinal , Obesidade Infantil , Fenóis , Humanos , Compostos Benzidrílicos/efeitos adversos , Obesidade Infantil/epidemiologia , Obesidade Infantil/microbiologia , Fenóis/efeitos adversos , Fenóis/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Criança , Exposição Ambiental/efeitos adversosAssuntos
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
BACKGROUND Sodium-glucose co-transporter 2 inhibitors (SGLT2), such as empagliflozin, used to treat type 2 diabetes mellitus (DM), can increase the risk of infections, including urinary tract infections and osteomyelitis, especially in elderly patients. The use of SGLT2 inhibitors has been increasing dramatically in the last few years. Therefore, their adverse effects and complications have also been increasing. Herein, this report describes a 73-year-old man with type 2 DM treated with empagliflozin presenting with asymptomatic bacteriuria, vertebral osteomyelitis and iliopsoas abscess due to Klebsiella pneumoniae. CASE REPORT We report a 73-year-old man with DM on empagliflozin who presented with back pain of 1-month duration with elevated inflammatory markers. On lumbar spine magnetic resonance imaging (MRI), he was found to have lumbar vertebral osteomyelitis and left iliopsoas abscess. His symptoms were improved with abscess drainage and antimicrobial therapy. The source of infection was most likely asymptomatic bacteriuria, which may have been secondary to empagliflozin treatment, as evidenced by the urine, the blood, the bone and abscess cultures revealing growth of Klebsiella pneumoniae with the same susceptibility profile. CONCLUSIONS This particular case reinforces the significance of potential complications of DM and SGLT2 inhibitors' adverse effects, especially the increased risk of infections, and can aid clinicians in expanding the differential and enabling them to reach an accurate diagnosis and appropriate management. Although vertebral osteomyelitis is a less common cause of back pain, physicians should keep it in the differential diagnosis whenever a patient's back pain is chronic and associated with motor weakness.
Assuntos
Bacteriúria , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Glucosídeos , Infecções por Klebsiella , Klebsiella pneumoniae , Osteomielite , Abscesso do Psoas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Idoso , Diabetes Mellitus Tipo 2/complicações , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Abscesso do Psoas/microbiologia , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/diagnóstico , Osteomielite/microbiologia , Osteomielite/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Bacteriúria/tratamento farmacológico , Vértebras Lombares , Imageamento por Ressonância MagnéticaRESUMO
Background: Evidence from animal experiments and epidemiological studies has reported controversial results about the effects of prenatal bisphenols (BPs) exposure on childhood thyroid function. This study aims to explore the associations of prenatal exposure to BPs with thyroid-related hormones (THs) in newborns and early childhood, with a particular focus on the sex-dependent and exposure level effects. Methods: Correlated studies were systematically searched from PubMed, Web of Science, Medline, Cochrane, and Embase until February 21, 2024. The exposures assessed include bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), bisphenol AF (BPAF), and tetrachlorobisphenol A (TCBPA). THs measured were thyroid stimulating hormone (TSH), total tri-iodothyronine (TT3), total thyroxine (TT4), free tri-iothyronine (FT3), and free thyroxine (FT4). Effect estimates were quantified using coefficients from multivariable regression models. Statistical analyses were completed using Stata 16.0. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). Results: Eleven cohort studies comprising 5,363 children were included in our meta-analysis. Prenatal bisphenol concentrations were statistically significant related to alterations in thyroid hormones in children, exclusively in female offspring, including reduced TSH (ß = -0.020, 95% CI: -0.036, -0.005) and increased TT3 levels (ß = 0.011, 95% CI: 0.001, 0.021), and exposure to high concentration of bisphenols (>1.5 ug/g creatinine) significantly reduced FT3 levels in children (ß = -0.011, 95% CI: -0.020, -0.003). Conclusion: Prenatal bisphenol exposure is linked to alterations in thyroid hormone levels in girls, necessitating enhanced measures to control bisphenol exposure levels during pregnancy for child health protection. Systematic Review Registration: https://inplasy.com, identifier INPLASY202450129.
Assuntos
Compostos Benzidrílicos , Exposição Materna , Fenóis , Efeitos Tardios da Exposição Pré-Natal , Glândula Tireoide , Criança , Feminino , Humanos , Gravidez , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/sangue , Disruptores Endócrinos/efeitos adversos , Exposição Materna/efeitos adversos , Fenóis/efeitos adversos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/sangue , Sulfonas , Testes de Função Tireóidea , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , MasculinoRESUMO
OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis. RESEARCH AND DESIGN METHODS: This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Global myocardial strain was assessed by feature tracking; cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); and cardiac tissue inflammation was assessed by T2 mapping. RESULTS: Between the baseline and 12-month time point, plasma IL-1B was reduced (- 1.8 pg/mL, P = 0.003) while ketones were increased (0.26 mM, P = 0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (- 158.9 pmole/min/106 cells, P = 0.0497 vs. - 5.2 pmole/min/106 cells, P = 0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. Global myocardial strain, ECV and T2 relaxation time did not change in both study groups. GOV REGISTRATION: NCT03782259.
Assuntos
Compostos Benzidrílicos , Biomarcadores , Diabetes Mellitus Tipo 2 , Glucosídeos , Mediadores da Inflamação , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Mediadores da Inflamação/sangue , Biomarcadores/sangue , Fatores de Tempo , Anti-Inflamatórios/uso terapêutico , Fibrose , Inflamação/tratamento farmacológico , Inflamação/sangue , Inflamação/diagnóstico , Método Duplo-Cego , Miocárdio/patologia , Miocárdio/metabolismo , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/prevenção & controle , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/sangueRESUMO
OBJECTIVE: To assess a systematic implementation approach for introducing dapagliflozin to individuals with heart failure and reduced ejection fraction in an outpatient clinical setting. METHODS: Retrospective medical record data were analysed. All individuals diagnosed with heart failure who resided within the hospital catchment area and had visited cardiology or internal medicine department between 2010 and 2019 were screened by using the main inclusion criteria from the DAPA-HF trial. The effectiveness of the previously described seven-step systematic implementation approach was assessed by the proportion receiving information letter, dapagliflozin treatment, follow-ups at 2-12 weeks and 12 months post-dapagliflozin initiation, persistence on dapagliflozin, adverse events, and reasons for discontinuation. RESULTS: Of the 2433 individuals, 352 met the main DAPA-HF trial criteria in step 2. After exclusions in steps 3 and 4, 191 individuals remained. Of these, 158 were invited for eligibility discussion in step 5, with 107 having received an information letter beforehand. In step 6, dapagliflozin was prescribed to 69 individuals, and in step 7, follow-ups were conducted with 56 individuals at 2-12 weeks and 62 individuals at 12 months. Sixty out of 69 persisted on dapagliflozin after 12 months. Adverse events were reported by nine individuals. Discontinuation was attributed to reasons such as urinary tract infections, genital or abdominal discomfort, and hypotension. CONCLUSION: The systematic introduction of dapagliflozin to heart failure patients was effective. Despite this, challenges in uniformly implementing procedures across patients were evident, emphasizing the necessity for a systematic implementation approach.
Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Humanos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Feminino , Masculino , Idoso , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisAssuntos
Diabetes Mellitus Tipo 2 , Transplante de Rim , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Nefropatias Diabéticas , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Resultado do Tratamento , Idoso , Transplantados , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , AdultoRESUMO
The human body is commonly exposed to bisphenol A (BPA), which is widely used in consumer and industrial products. BPA is an endocrine-disrupting chemical that has adverse effects on human health. In particular, many studies have shown that BPA can cause various neurological disorders by affecting brain development and neural function during prenatal, infancy, childhood, and adulthood exposure. In this review, we discussed the correlation between BPA and neurological disorders based on molecular cell biology, neurophysiology, and behavioral studies of the effects of BPA on brain development and function. Recent studies, both animal and epidemiological, strongly indicate that BPA significantly impacts brain development and function. It hinders neural processes, such as proliferation, migration, and differentiation during development, affecting synaptic formation and activity. As a result, BPA is implicated in neurodevelopmental and neuropsychiatric disorders like autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia.
Assuntos
Compostos Benzidrílicos , Doenças do Sistema Nervoso , Fenóis , Humanos , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Fenóis/efeitos adversos , Animais , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/patologia , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologiaAssuntos
Estado Terminal , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Insuficiência de Múltiplos Órgãos/etiologia , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Transportador 2 de Glucose-SódioRESUMO
AIM: To evaluate the efficacy and tolerability of an initial triple combination therapy (TCT) compared with conventional stepwise add-on therapy (SAT) in patients with newly diagnosed type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, randomized, 104-week, open-label trial randomized 105 patients with drug-naïve T2D (with HbA1c level ≥ 8.0%, < 11.0%) to the TCT (1000 mg of metformin, 10 mg of dapagliflozin and 5 mg of saxagliptin once daily) or SAT (initiated with metformin, followed by glimepiride and sitagliptin) groups. The primary outcome was the proportion of patients who achieved an HbA1c level of less than 6.5% without hypoglycaemia, weight gain of 5% or higher, or discontinuation of drugs because of adverse events at week 104. RESULTS: HbA1c reduction from baseline at week 104 was similar between the groups (the least squares mean change was -2.56% in the TCT group vs. -2.75% in the SAT group). The primary outcome was achieved in 39.0% and 17.1% of the TCT and SAT groups, respectively, with a risk difference of 22.0 (95% confidence interval 3.0, 40.8; P = .027). HbA1c level less than 6.5% at week 104 was 46.3% in both the TCT and SAT groups, whereas the incidence of hypoglycaemia, weight gain, or discontinuation of drugs was 16.7% and 62.0% in the TCT and SAT groups, respectively (P < .001). TCT was well-tolerated and had fewer adverse events than SAT. CONCLUSIONS: Among newly diagnosed patients with T2D, initial TCT effectively lowered HbA1c levels with higher tolerability and safety than SAT for 104 weeks, suggesting a novel strategy for initial combination therapy in T2D patients.
Assuntos
Adamantano , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Dipeptídeos , Quimioterapia Combinada , Glucosídeos , Hemoglobinas Glicadas , Hipoglicemiantes , Metformina , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Metformina/uso terapêutico , Metformina/administração & dosagem , Metformina/efeitos adversos , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Masculino , Feminino , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Pessoa de Meia-Idade , Dipeptídeos/efeitos adversos , Dipeptídeos/administração & dosagem , Dipeptídeos/uso terapêutico , Adamantano/análogos & derivados , Adamantano/administração & dosagem , Adamantano/efeitos adversos , Adamantano/uso terapêutico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Idoso , Resultado do Tratamento , Hipoglicemia/induzido quimicamente , Compostos de Sulfonilureia/uso terapêutico , Compostos de Sulfonilureia/administração & dosagem , Compostos de Sulfonilureia/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Adulto , Aumento de Peso/efeitos dos fármacos , Fosfato de Sitagliptina/uso terapêutico , Fosfato de Sitagliptina/administração & dosagem , Fosfato de Sitagliptina/efeitos adversosRESUMO
AIMS: To assess the comparative cardiovascular and renal effectiveness and safety of empagliflozin vs. dapagliflozin among patients with type 2 diabetes in routine clinical practice. METHODS AND RESULTS: Cohort study using data from nationwide registers in Sweden, Denmark, and Norway, from June 2014 to June 2021 included 141 065 new users of empagliflozin and 58 306 new users of dapagliflozin. Coprimary outcomes were major cardiovascular events (myocardial infarction, stroke, and cardiovascular death), heart failure (hospitalization or death because of heart failure) and serious renal events (renal replacement therapy, hospitalization for renal events, and death from renal causes). Secondary outcomes were the individual components of the primary outcomes, any cause death, and diabetic ketoacidosis. Use of empagliflozin vs. dapagliflozin was associated with similar risk of major cardiovascular events [adjusted incidence rate: 15.9 vs. 15.8 events per 1000 person-years; HR 1.02, (95% confidence interval 0.97-1.08)], heart failure [6.5 vs. 6.3 events per 1000 person-years; HR 1.05 (0.97-1.14)] and serious renal events [3.7 vs. 4.1 events per 1000 person-years; HR 0.97 (0.87-1.07)]. In secondary outcome analyses, the HRs for use of empagliflozin vs. dapagliflozin were 1.00 (0.93-1.07) for myocardial infarction, 1.03 (0.95-1.12) for stroke, 1.01 (0.92-1.13) for cardiovascular death, 1.06 (1.00-1.11) for any cause death, 0.77 (0.60-0.99) for renal replacement therapy, 1.20 (0.75-1.93) for renal death, 1.01 (0.90-1.12) for hospitalization for renal events and 1.12 (0.94-1.33) for diabetic ketoacidosis. CONCLUSION: Use of empagliflozin and dapagliflozin was associated with similar risk of cardiovascular and renal outcomes, mortality, and diabetic ketoacidosis.
Assuntos
Compostos Benzidrílicos , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Glucosídeos , Sistema de Registros , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Glucosídeos/efeitos adversos , Glucosídeos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/diagnóstico , Idoso , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Resultado do Tratamento , Fatores de Risco , Fatores de Tempo , Medição de Risco , Nefropatias Diabéticas/mortalidade , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/diagnóstico , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/mortalidade , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/diagnóstico , Países Escandinavos e Nórdicos/epidemiologia , Incidência , Dinamarca/epidemiologiaRESUMO
BACKGROUND: Bisphenols and phthalates are two classes of endocrine-disrupting chemicals (EDCs) thought to influence weight and adiposity. Limited research has investigated their influence on maternal weight changes, and no prior work has examined maternal fat mass. We examined the associations between exposure to these chemicals during pregnancy and multiple maternal weight and fat mass outcomes. METHODS: This study included a sample of 318 women enrolled in a Canadian prospective pregnancy cohort. Second trimester urinary concentrations of 2 bisphenols and 12 phthalate metabolites were quantified. Self-reported and measured maternal weights and measured skinfold thicknesses were used to calculate gestational weight gain, 3-months and 3- to 5-years postpartum weight retention, late pregnancy fat mass gain, total postpartum fat mass loss, and late postpartum fat mass retention. Adjusted robust regressions examined associations between chemicals and outcomes in the entire study population and sub-groups stratified by pre-pregnancy body mass index (BMI). Bayesian kernel machine regression examined chemical mixture effects. RESULTS: Among women with underweight or normal pre-pregnancy BMIs, MBzP was negatively associated with weight retention at 3- to 5-years postpartum (B = -0.04, 95%CI: -0.07, -0.01). Among women with overweight or obese pre-pregnancy BMIs, MEHP and MMP were positively associated with weight retention at 3-months and 3- to 5-years postpartum, respectively (B's = 0.12 to 0.63, 95%CIs: 0.02, 1.07). DEHP metabolites and MCNP were positively associated with late pregnancy fat mass gain and late postpartum fat mass retention (B's = 0.04 to 0.18, 95%CIs: 0.001, 0.32). Further, the mixture of EDCs was positively associated with late pregnancy fat mass gain. CONCLUSION: In this cohort, pre-pregnancy BMI was a key determinant of the associations between second trimester exposure to bisphenols and phthalates and maternal weight changes and fat accumulation. Investigations of underlying physiological mechanisms, windows of susceptibility, and impacts on maternal and infant health are needed.
Assuntos
Compostos Benzidrílicos , Índice de Massa Corporal , Fenóis , Ácidos Ftálicos , Humanos , Feminino , Fenóis/urina , Fenóis/efeitos adversos , Ácidos Ftálicos/urina , Gravidez , Adulto , Compostos Benzidrílicos/urina , Compostos Benzidrílicos/efeitos adversos , Estudos Prospectivos , Exposição Materna/efeitos adversos , Poluentes Ambientais/urina , Disruptores Endócrinos/urina , Adulto Jovem , Adiposidade/efeitos dos fármacos , CanadáRESUMO
Objective: To investigate the effect of Dapagliflozin, sodium-glucose cotransporter 2 inhibitor (SGLT2i), on contrast-induced acute kidney injury (CIAKI) in patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention(PCI). Methods: A cohort study. The clinical data of 366 patients with coronary heart disease combined with T2DM who underwent PCI in the Department of Cardiology, Tianjin University Chest Hospital, from June 2021 to June 2022 were retrospectively analyzed, including 218 males and 148 females, aged (64.6±11.0) years old. According to whether the patients had used Dapagliflozin or not, the selected patients were divided into SGLT2i group(n=124) and control group(n=242). The changes in cardiac indicators, renal function, and inflammatory response indicators before and 72 hours after PCI treatment were analyzed and compared between the two groups. The incidence rate of CIAKI in the two groups was analyzed, and the influencing factors of CIAKI were analyzed by multivariate logistic regression. The major adverse cardiac events (MACE) were recorded during the follow-up period of the two groups, and Kaplan-Meier survival analysis and log-rank test were used to compare the differences in MACE occurrence between the two group. Results: The left ventricular ejection fraction (LVEF) of the SGLT2i group was lower than that of the control group, and the proportion of patients with LVEF<45% and CIAKI risk score were higher than those of the control group, with statistical significance (all P<0.05). 72 h after PCI treatment, ß-2 Microglobulin(ß-2MG), cystatin-C(Cys-C), and neutrophil gelatinase-associated lipocalin (NGAL) in both groups were all increased compared to those before PCI treatment, with statistical significance (all P<0.05).ß-2MG, Cys-C, and NGAL in SGLT2i group were all lower than those in the control group, with statistical significance(all P<0.05).The levels of interleukin-6(IL-6), hypersensitive C-reactive protein (hs-CRP), and malondialdehyde in both groups of patients increased compared to preoperative levels, while the levels of superoxide dismutase (SOD) decreased compared to preoperative levels, with statistical significance (all P<0.05). The levels of IL-6, hs-CRP, and malondialdehyde in the SGLT2i group were lower than those in the control group, while SOD was higher than that in the control group, with statistical significance (all P<0.05). Among all patients included, 34 cases experienced CIAKI (9.8%), and the incidence of CIAKI in the SGLT2i group was lower than that in the control group [4.8% (6/124) vs 11.6% (28/242),P=0.037]. Multivariate logistic regression analysis showed that the use of dapagliflozin was a protective factor for CIAKI in T2DM patients receiving PCI treatment (OR=0.321, 95%CI: 0.127-0.816, P=0.017). After a follow-up of 14.0 (12.0, 16.2) months, the incidence of MACE in SGLT2i group was lower than that in the control group (7.3% vs 12.8%, P=0.048). Conclusions: Dapagliflozin may reduce the risk of CIAKI and MACE in T2DM patients after PCI treatment. Its mechanism may be related to the anti-inflammatory and antioxidant effects of SGLT2i.
Assuntos
Injúria Renal Aguda , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Glucosídeos , Intervenção Coronária Percutânea , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Feminino , Intervenção Coronária Percutânea/efeitos adversos , Glucosídeos/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Meios de Contraste/efeitos adversos , Doença da Artéria Coronariana , Estudos de CoortesRESUMO
Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. Epidemiological studies have reported that exposure of the population to environmental endocrine-disrupting chemicals (EDCs) is associated with NAFLD. However, EDCs are of different types, and there are inconsistencies in the relevant evidence and descriptions, which have not been systematically summarized so far. Therefore, this study aimed to determine the association between population exposure to EDCs and NAFLD. Three databases, including PubMed, Web of science, and Embase were searched, and 27 articles were included in this study. Methodological quality, heterogeneity, and publication bias of the included studies were assessed using the Newcastle-Ottawa scale, I2 statistics, Begg's test, and Egger's test. The estimated effect sizes of the included studies were pooled and evaluated using the random-effects model (I2 > 50â¯%) and the fixed-effects model ( I2 < 50â¯%). The pooled-estimate effect sizes showed that population exposure to Phthalates (PAEs) (OR = 1.18, 95â¯% CI:1.03-1.34), cadmium (Cd) (OR = 1.37, 95â¯% CI:1.09-1.72), and bisphenol A (OR = 1.43, 95â¯% CI:1.24-1.65) were positively correlated with the risk of NAFLD. Exposure to mercury (OR =1.46, 95â¯% CI:1.17-1.84) and Cd increased the risk of "elevated alanine aminotransferase". On the contrary, no significant association was identified between perfluoroalkyl substances (OR =0.99, 95â¯% CI:0.93-1.06) and NAFLD. However, female exposure to perfluorooctanoic acid (OR =1.82, 95â¯% CI:1.01-3.26) led to a higher risk of NAFLD than male exposure. In conclusion, this study revealed that EDCs were risk factors for NAFLD. Nonetheless, the sensitivity analysis results of some of the meta-analyses were not stable and demonstrated high heterogeneity. The evidence for these associations is limited, and more large-scale population-based studies are required to confirm these findings.