Assuntos
Diabetes Mellitus Tipo 2, Peptídeos Semelhantes ao Glucagon, Hipoglicemiantes, Humanos, Peptídeos Semelhantes ao Glucagon/uso terapêutico, Peptídeos Semelhantes ao Glucagon/efeitos adversos, Peptídeos Semelhantes ao Glucagon/administração & dosagem, Diabetes Mellitus Tipo 2/tratamento farmacológico, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/efeitos adversos, Hipoglicemiantes/administração & dosagemRESUMO
Immunoglobulin A (IgA) nephropathy is a common glomerulonephritis, but its treatment remains matter of debate. Recommendation for corticosteroids has been supported, but renin-angiotensin inhibitors, RAAS, and sodium-glucose co-transporter 2 inhibitors (SGLT2i) are increasingly used because of a better benefit/safety balance in comparison with systemic steroids and immunosuppressive treatments. In this case report, a patient with type 2 diabetes (T2DM) and biopsy-proven nephrotic IgA-related nephropathy documented a rapid meaningful reduction of proteinuria and the effect was persistent for 2 years, after receiving the treatment with a GLP1-RA on top of the previous treatment with ACE-inhibitors and SGLT2-i. Considering the beneficial effects of GLP1-RA in diabetes related chronic kidney disease, the present case report supports the notion that these drugs could also represent a beneficial treatment option in IgA nephropathy.
Assuntos
Inibidores da Enzima Conversora de Angiotensina, Diabetes Mellitus Tipo 2, Nefropatias Diabéticas, Quimioterapia Combinada, Glomerulonefrite por IGA, Proteinúria, Inibidores do Transportador 2 de Sódio-Glicose, Humanos, Glomerulonefrite por IGA/tratamento farmacológico, Glomerulonefrite por IGA/complicações, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Diabetes Mellitus Tipo 2/complicações, Diabetes Mellitus Tipo 2/tratamento farmacológico, Inibidores da Enzima Conversora de Angiotensina/uso terapêutico, Proteinúria/tratamento farmacológico, Proteinúria/etiologia, Nefropatias Diabéticas/tratamento farmacológico, Masculino, Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas, Pessoa de Meia-IdadeRESUMO
BACKGROUND: Shared decision-making (SDM) is a patient-centred approach to improve the quality of care. An essential requirement for the SDM process is to be fully aware of patient information needs. OBJECTIVES: Our study aimed to assess patient information needs for new antidiabetic medications using the best-worst scaling (BWS) experiment. METHODS: BWS tasks were developed according to a literature review and the focus group discussion. We used a balanced incomplete block design and blocking techniques to generate choice sets. The final BWS contains 11 attributes, with 6-choice scenarios in each block. The one-to-one, face-to-face BWS survey was conducted among type 2 diabetic patients in Jiangsu Province. Results were analyzed using count-based analysis and modelling approaches. We also conducted a subgroup analysis to observe preference heterogeneity. RESULTS: Data from 539 patients were available for analysis. The most desired information domain was the comparative effectiveness of new antidiabetic medications. It consists of the incidence of macrovascular complications, the length of extended life years, changes in health-related quality of life, the incidence of microvascular complications, and the control of glycated haemoglobin. Of all the attributes, the incidence of macrovascular complications was the primary concern. Patients' glycemic control and whether they had diabetes complications exerted a significant influence on their information needs. CONCLUSIONS: Information on health benefits is of critical significance for diabetic patients. Patients have different information needs as their disease progresses. Personalized patient decision aids that integrate patient information needs and provide evidence of new antidiabetic medications are worthy of being established. PATIENT OR PUBLIC CONTRIBUTION: Before data collection, a pilot survey was carried out among diabetic patients to provide feedback on the acceptability and intelligibility of the attributes.
Assuntos
Tomada de Decisão Compartilhada, Diabetes Mellitus Tipo 2, Hipoglicemiantes, Humanos, Hipoglicemiantes/uso terapêutico, Diabetes Mellitus Tipo 2/tratamento farmacológico, China, Masculino, Pessoa de Meia-Idade, Feminino, Grupos Focais, Idoso, Inquéritos e Questionários, Avaliação das Necessidades, Participação do Paciente, AdultoRESUMO
AIM: Bariatric surgery is an effective tool for weight loss and for improving weight related co-morbidities. Changes in medication usage after a silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) compared with laparoscopic sleeve gastrectomy (LSG) are unknown. METHODS: This was a single-centre, double-blind, randomised controlled trial. Patients were randomised to either SR-LRYGB or LSG. A medication history was obtained at regular follow-up intervals, and mean numbers of prescribed medications were analysed over 5 years. Poisson regression and generalised estimating equations were used to test for statistically significant changes in usage. RESULTS: After eight patients were lost to follow-up, data from 52 patients in each group were available for analysis. There was no difference between the SR-LRYGB or LSG groups in the number of medications prescribed, with the exception of oral glucose-lowering medications, where there was a greater decrease after SR-LRYGB compared to LSG (79% vs 55% respectively) from baseline to 5 years. At 5 years, total medication prescribed was down 10% from pre-operative levels. Prescribed insulin decreased by 72%, and cardiovascular medication decreased by 56% compared to baseline. Prescriptions for analgesia increased by 50%, psychiatric medications by 133% and proton-pump inhibitors by 81%. CONCLUSION: Both SR-LRYGB and LSG reduced requirement for diabetic and cardiovascular medications, but increased requirement for nutritional supplementation, analgesia and psychiatric medications. There was a greater reduction in oral anti-diabetic medication prescriptions following SR-LRYGB compared to LSG, but no other difference in medication usage between surgical groups was found.
Assuntos
Diabetes Mellitus Tipo 2, Gastrectomia, Derivação Gástrica, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/cirurgia, Derivação Gástrica/métodos, Feminino, Masculino, Gastrectomia/métodos, Método Duplo-Cego, Pessoa de Meia-Idade, Adulto, Obesidade Mórbida/cirurgia, Hipoglicemiantes/uso terapêutico, Redução de Peso, Laparoscopia/métodos, Resultado do TratamentoRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).
Assuntos
Compostos Benzidrílicos, Diabetes Mellitus Tipo 2, Peptídeos Semelhantes ao Glucagon, Glucosídeos, Hepatopatia Gordurosa não Alcoólica, Humanos, Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico, Hepatopatia Gordurosa não Alcoólica/complicações, Glucosídeos/uso terapêutico, Glucosídeos/efeitos adversos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/complicações, Peptídeos Semelhantes ao Glucagon/uso terapêutico, Compostos Benzidrílicos/uso terapêutico, Compostos Benzidrílicos/efeitos adversos, Pessoa de Meia-Idade, Masculino, Método Duplo-Cego, Feminino, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/efeitos adversos, Adulto, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Quimioterapia Combinada, Glicemia/metabolismo, Idoso, Resultado do TratamentoRESUMO
In community nursing, the administration of insulin for people with type 2 diabetes can be delegated by registered nurses to healthcare support workers. Although a voluntary framework in England provides national guidance, little is known about its uptake. The project aim was to determine the roll-out, characteristics and support needs in relation to the delegation of insulin administration in community settings. An online survey was disseminated to community nursing services in England via social media and nursing networks. Of the 115 responding organisations, 81% (n=93) had an insulin delegation programme, with most initiated since 2018. From these services, 41% (n=3704) of insulin injections were delegated daily, with benefits for patients, staff and services reported, along with some challenges. Delegation of insulin administration is an established and valued initiative. Awareness of the national voluntary framework is increasing. National guidance is considered important to support governance arrangements and safety.
Assuntos
Enfermagem em Saúde Comunitária, Diabetes Mellitus Tipo 2, Insulina, Humanos, Inglaterra, Insulina/administração & dosagem, Insulina/uso terapêutico, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/enfermagem, Inquéritos e Questionários, Medicina Estatal, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Delegação Vertical de Responsabilidades ProfissionaisRESUMO
PURPOSE: This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin. METHODS: Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters. RESULTS: The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up. CONCLUSIONS: The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis.
Assuntos
Compostos Benzidrílicos, Diabetes Mellitus Tipo 2, Glucosídeos, Metformina, Pancreatite, Compostos de Sulfonilureia, Humanos, Compostos Benzidrílicos/efeitos adversos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/epidemiologia, Pancreatite/induzido quimicamente, Pancreatite/epidemiologia, Glucosídeos/efeitos adversos, Glucosídeos/uso terapêutico, Glucosídeos/administração & dosagem, Compostos de Sulfonilureia/efeitos adversos, Compostos de Sulfonilureia/uso terapêutico, Masculino, Feminino, Pessoa de Meia-Idade, Idoso, Metformina/efeitos adversos, Metformina/administração & dosagem, Metformina/uso terapêutico, Hipoglicemiantes/efeitos adversos, Hipoglicemiantes/administração & dosagem, Bases de Dados Factuais, Incidência, Vigilância de Produtos Comercializados/estatística & dados numéricos, Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Adulto, Estados Unidos/epidemiologia, Pontuação de PropensãoRESUMO
This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes-related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high-fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty-six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury.
Assuntos
Glicemia, Diabetes Mellitus Experimental, Diabetes Mellitus Tipo 2, Inflamação, Inulina, Rim, Metabolômica, Camundongos Endogâmicos ICR, Estresse Oxidativo, Animais, Inulina/farmacologia, Diabetes Mellitus Tipo 2/complicações, Diabetes Mellitus Tipo 2/sangue, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/metabolismo, Diabetes Mellitus Experimental/sangue, Diabetes Mellitus Experimental/tratamento farmacológico, Diabetes Mellitus Experimental/complicações, Diabetes Mellitus Experimental/metabolismo, Camundongos, Masculino, Glicemia/metabolismo, Glicemia/efeitos dos fármacos, Rim/efeitos dos fármacos, Rim/metabolismo, Rim/patologia, Estresse Oxidativo/efeitos dos fármacos, Nefropatias Diabéticas/tratamento farmacológico, Nefropatias Diabéticas/metabolismo, Nefropatias Diabéticas/sangue, Nefropatias Diabéticas/patologia, Ácidos Graxos Voláteis/metabolismo, Dieta Hiperlipídica, Nitrogênio da Ureia SanguíneaRESUMO
Type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), obesity (OB) and hypertension (HT) are categorized as metabolic disorders (MDs), which develop independently without distinct borders. Herein, we examined the gut microbiota (GM) and Saururus chinensis (SC) to confirm their therapeutic effects via integrated pharmacology. The overlapping targets from the four diseases were determined to be key protein coding genes. The protein-protein interaction (PPI) networks, and the SC, GM, signalling pathway, target and metabolite (SGSTM) networks were analysed via RPackage. Additionally, molecular docking tests (MDTs) and density functional theory (DFT) analysis were conducted to determine the affinity and stability of the conformer(s). TNF was the main target in the PPI analysis, and equol derived from Lactobacillus paracasei JS1 was the most effective agent for the formation of the TNF complex. The SC agonism (PPAR signalling pathway), and antagonism (neurotrophin signalling pathway) by SC were identified as agonistic bioactives (aromadendrane, stigmasta-5,22-dien-3-ol, 3,6,6-trimethyl-3,4,5,7,8,9-hexahydro-1H-2-benzoxepine, 4α-5α-epoxycholestane and kinic acid), and antagonistic bioactives (STK734327 and piclamilast), respectively, via MDT. Finally, STK734327-MAPK1 was the most favourable conformer according to DFT. Overall, the seven bioactives from SC and equol that can be produced by Lactobacillus paracasei JS1 can exert synergistic effects on these four diseases.
Assuntos
Diabetes Mellitus Tipo 2, Microbioma Gastrointestinal, Hipertensão, Hepatopatia Gordurosa não Alcoólica, Obesidade, Saururaceae, Microbioma Gastrointestinal/efeitos dos fármacos, Hepatopatia Gordurosa não Alcoólica/microbiologia, Hepatopatia Gordurosa não Alcoólica/metabolismo, Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico, Obesidade/microbiologia, Obesidade/metabolismo, Diabetes Mellitus Tipo 2/microbiologia, Diabetes Mellitus Tipo 2/metabolismo, Diabetes Mellitus Tipo 2/tratamento farmacológico, Hipertensão/microbiologia, Hipertensão/metabolismo, Hipertensão/tratamento farmacológico, Animais, Saururaceae/química, Saururaceae/metabolismo, Simulação de Acoplamento Molecular, Humanos, Mapas de Interação de ProteínasRESUMO
BACKGROUND: Studies have shown that RASGRP1 was potently associated with the onset of type 2 diabetes mellitus (T2DM), and RASGRP1 rs7403531 was significantly correlated with islet function in T2DM patients. However, the effect of RASGRP1 polymorphism on blood glucose and blood pressure in T2DM patients after continuous treatment has yet to be fully elucidated. OBJECTIVE: This study aimed to explore the association between RASGRP1 genetic polymorphism and cardiovascular complications in T2DM patients, so as to provide more evidence for the individualized treatment of T2DM patients. METHODS: We retrospectively analyzed a large-scale multicenter drug clinical study cohort that based on a 2 × 2 factorial (glucose control axis and blood pressure lowering axis) randomized controlled design, with follow-up for 5 years. The major vascular endpoint events included cardiovascular death, non-fatal stroke, coronary heart disease, new-onset or worsening renal disease, and diabetic retinopathy. RASGRP1 rs12593201, rs56254815 and rs7403531 were finally selected as candidate single nucleotide polymorphisms. Mixed linear model and Cox hazard ratio (HR) model were used for data analysis with IBM SPSS (version 20.0 for windows; Chicago, IL). RESULTS: Our study enrolled 1357 patients with high-risk diabetes, with a mean follow-up duration of 4.8 years. RASGRP1 rs7403531 was associated with vascular events in hypoglycemic and antihypertensive therapy. Specifically, compared with CC carriers, patients with CT/TT genotype had fewer major microvascular events (HR = 0.41, 95% confidence interval (CI) 0.21-0.80, P = 0.009), and reduced the risk of major eye disease events (HR = 0.44, 95% CI 0.20-0.94, P = 0.03). For glucose lowering axis, CT/TT carriers had a lower risk of secondary nephropathy (HR = 0.48, 95% CI 0.25-0.92, P = 0.03) in patients with standard glycemic control. For blood pressure lowering axis, all cerebrovascular events (HR = 2.24, 95% CI 1.11-4.51, P = 0.025) and stroke events (HR = 2.07, 95% CI 1.03-4.15, P = 0.04) were increased in patients with CC genotype compared to those with CT/TT genotype in the placebo group, respectively. Furthermore, patients with CC genotype showed a reduced risk of major cerebrovascular events in antihypertensive group (HR = 0.36, 95% CI 0.15-0.86, P = 0.021). For RASGRP1 rs56254815, compared with the AA genotype carriers, the systolic blood pressure of AG/GG carriers in the antihypertensive group decreased by 1.5mmhg on average (P = 0.04). In the placebo group, the blood pressure of AG/GG carriers was 1.7mmHg higher than that of AA carriers (P = 0.02). CONCLUSION: We found that patients with G allele of RASGRP1 (rs56254815) showed a better antihypertensive therapy efficacy in T2DM patients. The rs7403531 T allele could reduce the risk of major microvascular events and major eye diseases in T2DM patients receiving either hypoglycemic or antihypertensive therapy. Our findings suggest that RASGRP1 genetic polymorphism might predict the cardiovascular complications in T2DM patients.
Assuntos
Anti-Hipertensivos, Glicemia, Pressão Sanguínea, Diabetes Mellitus Tipo 2, Predisposição Genética para Doença, Controle Glicêmico, Fatores de Troca do Nucleotídeo Guanina, Polimorfismo de Nucleotídeo Único, Humanos, Masculino, Feminino, Pessoa de Meia-Idade, Anti-Hipertensivos/uso terapêutico, Anti-Hipertensivos/efeitos adversos, Diabetes Mellitus Tipo 2/genética, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/diagnóstico, Diabetes Mellitus Tipo 2/complicações, Diabetes Mellitus Tipo 2/sangue, China/epidemiologia, Glicemia/metabolismo, Glicemia/efeitos dos fármacos, Idoso, Estudos Retrospectivos, Fatores de Troca do Nucleotídeo Guanina/genética, Fatores de Risco, Resultado do Tratamento, Controle Glicêmico/efeitos adversos, Pressão Sanguínea/efeitos dos fármacos, Pressão Sanguínea/genética, Povo Asiático/genética, Angiopatias Diabéticas/genética, Angiopatias Diabéticas/diagnóstico, Medição de Risco, Fenótipo, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/efeitos adversos, Fatores de Tempo, Biomarcadores/sangue, Estudos de Associação Genética, Hipertensão/genética, Hipertensão/tratamento farmacológico, Hipertensão/fisiopatologia, Hipertensão/diagnóstico, Proteínas de Ligação a DNA/genética, População do Leste AsiáticoRESUMO
Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after directacting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/ type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.
Assuntos
Antivirais, Glicemia, Hemoglobinas Glicadas, Hepatite C Crônica, Resposta Viral Sustentada, Humanos, Feminino, Antivirais/uso terapêutico, Hepatite C Crônica/tratamento farmacológico, Hepatite C Crônica/sangue, Masculino, Pessoa de Meia-Idade, Hemoglobinas Glicadas/análise, Glicemia/análise, Glicemia/efeitos dos fármacos, Idoso, Estudos Prospectivos, Resultado do Tratamento, Hepacivirus/genética, Hepacivirus/efeitos dos fármacos, Brasil, Adulto, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/sangueRESUMO
OBJECTIVE: Tirzepatide is an injectable peptide approved by the US Food and Drug Administration for the treatment of Type 2 diabetes (T2DM). Its weight-loss effect primarily targets fat reduction; however, such effect on patients with chronic kidney disease (CKD) undergoing haemodialysis (HD) has not been reported. METHODS: Nine patients with CKD undergoing HD received weekly tirzepatide doses (2.5-7.5 mg) once a week. Evaluations encompassed tirzepatide's impact on dry weight (DW) and body composition assessed at baseline and study conclusion using bioelectrical impedance analysis. This longitudinal study included nine patients, with a median age of 53 years and median HD duration of 4 years. RESULTS: Tirzepatide treatment significantly decreased glycated albumin compared with the value at baseline (22.7 ± 5.4 vs. 18.3 ± 2.5%, p = 0.028, respectively). Significant reductions were observed in DW (-1.0 kg, p = 0.024) and body mass index (-0.6 kg/m2, p = 0.050) following tirzepatide administration. Total fat mass was also reduced, but not significantly (- 2.51% from baseline, p = 0.214). In contrast, skeletal muscle mass was not decreased (-1.02% from baseline, p = 0.722). No serious side effects other than nausea were observed during the study period. CONCLUSION: Tirzepatide effectively provides good glycaemic control in T2DM patients undergoing HD, decreasing DW by reducing body fat mass without increasing frailty risk.
Assuntos
Diabetes Mellitus Tipo 2, Controle Glicêmico, Diálise Renal, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/complicações, Pessoa de Meia-Idade, Masculino, Feminino, Estudos Retrospectivos, Controle Glicêmico/métodos, Adulto, Idoso, Composição Corporal, Insuficiência Renal Crônica/terapia, Insuficiência Renal Crônica/complicações, Glicemia/metabolismo, Estudos Longitudinais, Hipoglicemiantes/administração & dosagemRESUMO
INTRODUCTION: This study aimed to assess and compare the prevalence of diabetes complications between men and women with Type 2 diabetes (T2D), as well as how gender relates to these complications. METHODS: In this cross-sectional study, complications of diabetes, including coronary artery disease (CAD), retinopathy, neuropathy and diabetic kidney disease (DKD), were evaluated in 1867 participants with T2D. Additionally, baseline characteristics of the individuals, including anthropometric measurements, metabolic parameters and the use of dyslipidaemia drugs and antihyperglycaemic agents, were assessed. Gender differences in complications were examined using the chi-squared test. Multivariate logistic regression was employed to investigate the relationship between gender and T2D complications, with and without adjusting for the characteristics of the studied population. RESULTS: In the studied population, 62.1% had at least one complication, and complications were 33.5% for DKD, 29.6% for CAD, 22.9% for neuropathy and 19.1% for retinopathy. The prevalence of CAD and neuropathy was higher in men. However, DKD and retinopathy were more prevalent among women. Odds ratios of experiencing any complication, CAD and retinopathy in men compared with women were 1.57 (95% CI: 1.27-2.03), 2.27 (95% CI: 1.72-2.99) and 0.72 (95% CI: 0.52-0.98), respectively, after adjusting for demographic factors, anthropometric measures, metabolic parameters and the consumption of dyslipidaemia drugs and antihyperglycaemic agents. CONCLUSION: The prevalence of diabetes complications was significantly higher in men with diabetes, highlighting the need for better treatment adherence. CAD was associated with the male gender, whereas retinopathy was associated with the female gender. Men and women with diabetes should be monitored closely for CAD and retinopathy, respectively, regardless of their age, diabetes duration, anthropometric measures, laboratory findings and medications.
Assuntos
Diabetes Mellitus Tipo 2, Retinopatia Diabética, Humanos, Masculino, Feminino, Diabetes Mellitus Tipo 2/complicações, Diabetes Mellitus Tipo 2/tratamento farmacológico, Estudos Transversais, Pessoa de Meia-Idade, Idoso, Prevalência, Fatores Sexuais, Retinopatia Diabética/etiologia, Retinopatia Diabética/epidemiologia, Complicações do Diabetes/etiologia, Complicações do Diabetes/epidemiologia, Adulto, Neuropatias Diabéticas/etiologia, Neuropatias Diabéticas/epidemiologia, Nefropatias Diabéticas/etiologia, Nefropatias Diabéticas/epidemiologia, Doença da Artéria Coronariana/etiologiaRESUMO
The use of dulaglutide, a common medication for managing type 2 diabetes, rarely causes elevated pancreatic tumour markers. Here, we report the case of a woman in her mid-60s with diabetes for over 10 years. The patient presented with markedly elevated serum CA19-9 and CA242 levels revealed during a routine health examination despite being asymptomatic. She had been receiving dulaglutide injections for 16 months. Imaging and interventional assessments did not reveal any hepatobiliary, gastrointestinal or pancreatic neoplasm. After excluding alternate diagnoses, the patient was determined to exhibit an adverse reaction to dulaglutide use. Management involved the discontinuation of dulaglutide, which resulted in normalisation of serum CA19-9 and CA242 levels within 6 weeks. This case underscores the importance of discontinuing dulaglutide and monitoring changes in the biomarker levels in asymptomatic patients receiving dulaglutide, rather than immediately resorting to imaging and endoscopic examinations.
Assuntos
Antígeno CA-19-9, Diabetes Mellitus Tipo 2, Peptídeos Semelhantes ao Glucagon, Hipoglicemiantes, Fragmentos Fc das Imunoglobulinas, Proteínas Recombinantes de Fusão, Humanos, Proteínas Recombinantes de Fusão/efeitos adversos, Proteínas Recombinantes de Fusão/uso terapêutico, Proteínas Recombinantes de Fusão/administração & dosagem, Peptídeos Semelhantes ao Glucagon/análogos & derivados, Peptídeos Semelhantes ao Glucagon/efeitos adversos, Peptídeos Semelhantes ao Glucagon/uso terapêutico, Feminino, Fragmentos Fc das Imunoglobulinas/efeitos adversos, Fragmentos Fc das Imunoglobulinas/uso terapêutico, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/sangue, Antígeno CA-19-9/sangue, Pessoa de Meia-Idade, Hipoglicemiantes/efeitos adversos, Hipoglicemiantes/uso terapêutico, Neoplasias Pancreáticas/tratamento farmacológico, Neoplasias Pancreáticas/sangueRESUMO
INTRODUCTION: Studies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). The literature does not provide evidence specifically for patients with these conditions who are adding one of these medicines to two glucose-lowering medications (ie, as "third-step" therapy). We explored the effects of different third-step medications on cardiovascular outcomes in patients with diabetes and these comorbid conditions. Specifically, we compared third-step SGLT2 or GLP1 to third-step dipeptidyl peptidase-4 inhibitors (DPP4), insulin, or thiazolidinediones (TZD). RESEARCH DESIGN AND METHODS: We assembled a retrospective cohort of adults at five Kaiser Permanente sites with DM2 and ASCVD, CKD, or HF, initiating third-step treatment between 2016 and 2020. Propensity score weighted Poisson models were used to calculate adjusted rate ratios (ARRs) for all-cause mortality, incident major adverse cardiovascular event (MACE), and incident HF hospitalization in patients initiating SGLT2 or GLP1 compared with DPP4, insulin, or TZD. RESULTS: We identified 27 542 patients initiating third-step treatment with one or more of these conditions (19 958 with ASCVD, 14 577 with CKD, and 3919 with HF). ARRs for GLP1 and SGLT2 versus DPP4, insulin, and TZD in the patient subgroups ranged between 0.22 and 0.55 for all-cause mortality, 0.38 and 0.81 for MACE, and 0.46 and 1.05 for HF hospitalization. Many ARRs were statistically significant, and all significant ARRs showed a benefit (ARR <1) for GLP1 or SGLT2 when compared with DPP4, insulin, or TZD. CONCLUSIONS: Third-step SGLT2 and GLP1 are generally associated with a benefit for these outcomes in these patient groups when compared with third-step DPP4, insulin, or TZD. Our results add to evidence of a cardiovascular benefit of SGLT2 and GLP1 and could inform clinical guidelines for choosing third-step diabetes treatment.
Assuntos
Doenças Cardiovasculares, Diabetes Mellitus Tipo 2, Inibidores da Dipeptidil Peptidase IV, Receptor do Peptídeo Semelhante ao Glucagon 1, Hipoglicemiantes, Inibidores do Transportador 2 de Sódio-Glicose, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/complicações, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Feminino, Masculino, Estudos Retrospectivos, Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas, Pessoa de Meia-Idade, Idoso, Hipoglicemiantes/uso terapêutico, Doenças Cardiovasculares/mortalidade, Doenças Cardiovasculares/etiologia, Doenças Cardiovasculares/epidemiologia, Inibidores da Dipeptidil Peptidase IV/uso terapêutico, Glicemia/análise, Insuficiência Renal Crônica/epidemiologia, Seguimentos, Prognóstico, Insulina/uso terapêuticoRESUMO
INTRODUCTION: There has been increasing evidence that the gut microbiota is closely related to type 2 diabetes (T2D). Metformin (Met) is often used in combination with saxagliptin (Sax) and repaglinide (Rep) for the treatment of T2D. However, little is known about the effects of these combination agents on gut microbiota in T2D. RESEARCH DESIGN AND METHODS: A T2D mouse model induced by a high-fat diet (HFD) and streptozotocin (STZ) was employed. The T2D mice were randomly divided into six groups, including sham, Met, Sax, Rep, Met+Sax and Met+Rep, for 4 weeks. Fasting blood glucose level, serum biochemical index, H&E staining of liver, Oil red O staining of liver and microbiota analysis by 16s sequencing were used to access the microbiota in the fecal samples. RESULTS: These antidiabetics effectively prevented the development of HFD/STZ-induced high blood glucose, and the combination treatment had a better effect in inhibiting lipid accumulation. All these dosing regimens restored the decreasing ratio of the phylum Bacteroidetes: Firmicutes, and increasing abundance of phylum Desulfobacterota, expect for Met. At the genus level, the antidiabetics restored the decreasing abundance of Muribaculaceae in T2D mice, but when Met was combined with Rep or Sax, the abundance of Muribaculaceae was decreased. The combined treatment could restore the reduced abundance of Prevotellaceae_UCG-001, while Met monotherapy had no such effect. In addition, the reduced Lachnospiraceae_NK4A136_group was well restored in the combination treatment groups, and the effect was much greater than that in the corresponding monotherapy group. Therefore, these dosing regimens exerted different effects on the composition of gut microbiota, which might be associated with the effect on T2D. CONCLUSIONS: Supplementation with specific probiotics may further improve the hypoglycemic effects of antidiabetics and be helpful for the development of new therapeutic drugs for T2D.
Assuntos
Adamantano, Glicemia, Carbamatos, Diabetes Mellitus Experimental, Diabetes Mellitus Tipo 2, Dieta Hiperlipídica, Dipeptídeos, Microbioma Gastrointestinal, Hipoglicemiantes, Metformina, Piperidinas, Animais, Microbioma Gastrointestinal/efeitos dos fármacos, Metformina/farmacologia, Metformina/uso terapêutico, Camundongos, Dieta Hiperlipídica/efeitos adversos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/microbiologia, Hipoglicemiantes/farmacologia, Hipoglicemiantes/uso terapêutico, Diabetes Mellitus Experimental/tratamento farmacológico, Carbamatos/farmacologia, Dipeptídeos/farmacologia, Masculino, Adamantano/análogos & derivados, Adamantano/farmacologia, Adamantano/uso terapêutico, Piperidinas/farmacologia, Piperidinas/uso terapêutico, Glicemia/análise, Glicemia/efeitos dos fármacos, Camundongos Endogâmicos C57BL, Quimioterapia Combinada, EstreptozocinaRESUMO
INTRODUCTION: We hypothesized that multidisciplinary, proactive electronic consultation (MPE) could overcome barriers to prescribing guideline-directed medical therapies (GDMTs) for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS: We conducted an efficacy-implementation pilot study of MPE for T2D and CKD for primary care provider (PCP)-patient dyads at an academic health system. MPE included (1) a dashboard to identify patients without a prescription for sodium-glucose cotransporter-2 inhibitors (SGLT2i) and without a maximum dose prescription for renin-angiotensin-aldosterone system inhibitors (RAASi), (2) a multidisciplinary team of specialists to provide recommendations using e-consult templates, and (3) a workflow to deliver timely e-consult recommendations to PCPs. In-depth interviews were conducted with PCPs and specialists to assess feasibility, acceptability, and appropriateness of MPE and were analyzed using an iterative qualitative analysis approach to identify major themes. Prescription data were extracted from the electronic health record to assess preliminary effectiveness to increase GDMT. RESULTS: 20 PCPs agreed to participate, 18 PCPs received MPEs for one of their patients with T2D and CKD, and 16 PCPs and 2 specialists were interviewed. Major themes were as follows: appropriateness of prioritization of GDMT for T2D and CKD, acceptability of the content of the recommendations, PCP characteristics impact experience with MPE, acceptability and appropriateness of multidisciplinary collaboration, feasibility of MPE to overcome patient-specific barriers to GDMT, and appropriateness of workflow. At 6 months postbaseline, 7/18 (39%) patients were newly prescribed an SGLT2i, and 7/18 (39%) patients were either newly prescribed or had increased dose of RAASi. CONCLUSIONS: MPE was an acceptable and appropriate health system strategy to identify and address gaps in GDMT among patients with T2D and CKD. Adopting MPE could enhance GDMT, though PCPs raised feasibility concerns which could be improved with program enhancements, including follow-up e-consults for reinforcement, and administrative support for navigating system-level barriers.
Assuntos
Diabetes Mellitus Tipo 2, Encaminhamento e Consulta, Insuficiência Renal Crônica, Humanos, Insuficiência Renal Crônica/tratamento farmacológico, Diabetes Mellitus Tipo 2/tratamento farmacológico, Projetos Piloto, Masculino, Feminino, Pessoa de Meia-Idade, Guias de Prática Clínica como Assunto/normas, Atenção Primária à Saúde/métodos, Atenção Primária à Saúde/normas, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Idoso, Fidelidade a Diretrizes/estatística & dados numéricos, Equipe de Assistência ao Paciente, Seguimentos, Padrões de Prática Médica/normas, PrognósticoRESUMO
This study investigates the combined effect of vitamin C and chromium on BMI, lipid profile, LFTs and HbA1c of Diabetes Mellitus type 2 patients. This is randomized controlled trial study. For this study a total of 60 patients (n=28 female, n=32 male) Diabetes Mellitus type 2 patients were selected. They were divided into treatment group (vitamin C (500mg) Chromium (200µg) and control group (placebo) comprising thirty patients per group. Mean age in control group and treatment group is 33± 5.729 and 33±7.017 respectively. Statistical analysis showed significant results of lipid profile; total cholesterol (mg/dl) 198±66.1 P=0.008, High-Density Lipoprotein 38±7.5, P<0.001, Low Density Lipoprotein (LDL) (mg/dl) 105.1±22.4, P=0.002 and Triglycerides 191±64.3, P=0.02 are respectively. Levels of serum ALT (u/l) (34.7±9.1, P<0.001) and AST (u/l) (31.6 ±8.6, P<0.001) were significantly lower as compared to control group. HbA1c percentages were also normalized (5.45±0.2, P<.001) as compared to group 2. BMI values were also improved (P=0.01) after treatment. Combined supplementation of vitamin C and chromium reduce the plasma lipid percentage, blood glucose levels and also improve the ALT and AST functions.
Assuntos
Ácido Ascórbico, Índice de Massa Corporal, Cromo, Diabetes Mellitus Tipo 2, Hemoglobinas Glicadas, Humanos, Feminino, Masculino, Ácido Ascórbico/uso terapêutico, Cromo/uso terapêutico, Adulto, Diabetes Mellitus Tipo 2/sangue, Diabetes Mellitus Tipo 2/tratamento farmacológico, Hemoglobinas Glicadas/metabolismo, Hiperglicemia/tratamento farmacológico, Hiperglicemia/sangue, Hiperlipidemias/tratamento farmacológico, Hiperlipidemias/sangue, Lipídeos/sangue, Fígado/efeitos dos fármacos, Fígado/enzimologia, Fígado/metabolismo, Glicemia/efeitos dos fármacos, Glicemia/metabolismo, Alanina Transaminase/sangue, Aspartato Aminotransferases/sangue, Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice. DESIGN: Cohort study emulating a comparative effectiveness trial (target trial). SETTING: Linked primary care, hospital, and death data in England, 2015-21. PARTICIPANTS: 75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin. MAIN OUTCOME MEASURES: Primary outcome was absolute change in glycated haemoglobin A1c (HbA1c) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA1c at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures. RESULTS: 75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA1c values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA1c change between baseline and one year were -2.5 mmol/mol (95% confidence interval (CI) -3.7 to -1.3) for SGLT-2 inhibitors versus sulfonylureas and -3.2 mmol/mol (-4.6 to -1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking-the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43). CONCLUSIONS: This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints.
Assuntos
Diabetes Mellitus Tipo 2, Inibidores da Dipeptidil Peptidase IV, Hemoglobinas Glicadas, Hipoglicemiantes, Metformina, Inibidores do Transportador 2 de Sódio-Glicose, Compostos de Sulfonilureia, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Masculino, Feminino, Pessoa de Meia-Idade, Compostos de Sulfonilureia/uso terapêutico, Compostos de Sulfonilureia/administração & dosagem, Idoso, Metformina/uso terapêutico, Metformina/administração & dosagem, Hemoglobinas Glicadas/análise, Hemoglobinas Glicadas/metabolismo, Inibidores da Dipeptidil Peptidase IV/uso terapêutico, Inibidores da Dipeptidil Peptidase IV/administração & dosagem, Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico, Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem, Administração Oral, Taxa de Filtração Glomerular/efeitos dos fármacos, Inglaterra/epidemiologia, Quimioterapia Combinada, Resultado do Tratamento, Estudos de Coortes, Pesquisa Comparativa da Efetividade, Índice de Massa Corporal, Pressão Sanguínea/efeitos dos fármacosRESUMO
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) and SGLT1 inhibitors may have additional beneficial metabolic effects on circulating metabolites beyond glucose regulation, which could contribute to a reduction in the burden of cerebral small vessel disease (CSVD). Accordingly, we used Mendelian Randomization (MR) to examine the role of circulating metabolites in mediating SGLT2 and SGLT1 inhibition in CSVD. METHODS: Genetic instruments for SGLT1/2 inhibition were identified as genetic variants, which were both associated with the expression of encoding genes of SGLT1/2 inhibitors and glycated hemoglobin A1c (HbA1c) level. A two-sample two-step MR was used to determine the causal effects of SGLT1/2 inhibition on CSVD manifestations and the mediating effects of 1400 circulating metabolites linking SGLT1/2 inhibition with CSVD manifestations. RESULTS: A lower risk of deep cerebral microbleeds (CMBs) and small vessel stroke (SVS) was linked to genetically predicted SGLT2 inhibition. Better white matter structure integrity was also achieved, as evidenced by decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), as well as lower deep (DWMH) and periventrivular white matter hyperintensity (PWMH) volume. Inhibiting SGLT2 could also lessen the incidence of severe enlarged perivascular spaces (EPVS) located at white matter, basal ganglia (BG) and hippocampus (HIP). SGLT1 inhibition could preserve white matter integrity, shown as decreased MD of white matter and DWMH volume. The effect of SGLT2 inhibition on SVS and MD of white matter through the concentration of 4-acetamidobutanoate and the cholesterol to oleoyl-linoleoyl-glycerol (18:1 to 18:2) ratio, with a mediated proportion of 30.3% and 35.5% of the total effect, respectively. CONCLUSIONS: SGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism. Further mechanistic and clinical studies research are needed to validate our findings.
