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
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
Seipin is a key regulator of lipid metabolism, the deficiency of which leads to severe lipodystrophy. Hypothalamus is the pivotal center of brain that modulates appetite and energy homeostasis, where Seipin is abundantly expressed. Whether and how Seipin deficiency leads to systemic metabolic disorders via hypothalamus-involved energy metabolism dysregulation remains to be elucidated. In the present study, we demonstrated that Seipin-deficiency induced hypothalamic inflammation, reduction of anorexigenic pro-opiomelanocortin (POMC), and elevation of orexigenic agonist-related peptide (AgRP). Importantly, administration of rosiglitazone, a thiazolidinedione antidiabetic agent, rescued POMC and AgRP expression, suppressed hypothalamic inflammation, and restored energy homeostasis in Seipin knockout mice. Our findings offer crucial insights into the mechanism of Seipin deficiency-associated energy imbalance and indicates that rosiglitazone could serve as potential intervening agent towards metabolic disorders linked to Seipin.
Assuntos
Proteína Relacionada com Agouti, Metabolismo Energético, Subunidades gama da Proteína de Ligação ao GTP, Homeostase, Hipotálamo, Camundongos Knockout, Pró-Opiomelanocortina, Rosiglitazona, Animais, Camundongos, Hipotálamo/metabolismo, Metabolismo Energético/efeitos dos fármacos, Pró-Opiomelanocortina/genética, Pró-Opiomelanocortina/biossíntese, Proteína Relacionada com Agouti/genética, Subunidades gama da Proteína de Ligação ao GTP/genética, Rosiglitazona/farmacologia, Masculino, Doenças Neuroinflamatórias/etiologia, Camundongos Endogâmicos C57BL, Hipoglicemiantes/farmacologia, Hipoglicemiantes/uso terapêutico, Neuropeptídeos/genética, Neuropeptídeos/deficiência, Regulação da Expressão Gênica/efeitos dos fármacosRESUMO
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: Lifestyle changes, especially regarding diet quality and physical activity, are important in the management of type 2 diabetes (T2D). This mixed-methods study explores self-initiated lifestyle changes in patients with T2D who followed a periodic fasting-mimicking diet (FMD). METHODS: Quantitative data were obtained from the Fasting In diabetes Treatment trial (November 2018 to August 2021) in which 100 participants with T2D, using metformin only or no medication, were randomised to receive a monthly 5-day FMD for twelve months next to usual care, or usual care only. Diet quality and physical activity questionnaires were completed at baseline, six and twelve months. Changes over time were analysed using linear mixed models. Focus groups were organized with FMD participants to explore experiences regarding self-initiated lifestyle changes. The qualitative data was analysed using the Theoretical Domains Framework. RESULTS: Questionnaires were available from 49 FMD participants and 43 controls. No differences in diet quality were found. Total physical activity in the FMD participants changed from 34.6 to 38.5 h per week (h/wk) from baseline to twelve months, while in controls it changed from 34.9 to 29.0 h/wk (between group difference, p = 0.03). In six focus groups with FMD participants (n = 20), individual participants perceived the FMD as an encouragement for (minor) lifestyle changes. There were no barriers to behaviour change related to the FMD. Important facilitators of healthy behaviour were an increase in awareness of the impact of lifestyle on health (knowledge), better physical fitness (physical) and health improvement (reinforcement). Facilitators unrelated to the FMD included family support (social influences) and opportunities in the neighbourhood (environmental context and resources), while barriers unrelated to the FMD were experiencing health problems (physical) and social events (social influences). CONCLUSIONS: Using an FMD for five consecutive days per month did not affect diet quality in between FMD periods in quantitative analysis, but increased the number of hours per week spent on physical activity. Qualitative analysis revealed self-initiated improvements in both diet quality and physical activity in individual participants using an FMD. Healthcare professionals could use an FMD programme as a 'teachable moment' to stimulate additional lifestyle changes. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03811587. Registered 22 January 2019.
Assuntos
Diabetes Mellitus Tipo 2, Exercício Físico, Jejum, Humanos, Diabetes Mellitus Tipo 2/dietoterapia, Diabetes Mellitus Tipo 2/psicologia, Masculino, Feminino, Pessoa de Meia-Idade, Jejum/fisiologia, Exercício Físico/fisiologia, Exercício Físico/psicologia, Idoso, Estilo de Vida, Grupos Focais, Hipoglicemiantes/uso terapêutico, Hipoglicemiantes/administração & dosagem, Metformina/uso terapêutico, Dieta, Inquéritos e QuestionáriosRESUMO
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
BACKGROUND: This study aimed to examine the reporting quality of existing economic evaluations for negotiated glucose-lowering drugs (GLDs) included in China National Reimbursement Drug List (NRDL) using the Consolidated Health Economic Evaluation Reporting Standards 2013 (CHEERS 2013). METHODS: We performed a systematic literature research through 7 databases to identify published economic evaluations for GLDs included in the China NRDL up to March 2021. Reporting quality of identified studies was assessed by two independent reviewers based on the CHEERS checklist. The Kruskal-Wallis test and Mann-Whitney U test were performed to examine the association between reporting quality and characteristics of the identified studies. RESULTS: We have identified 24 studies, which evaluated six GLDs types. The average score rate of the included studies was 77.41% (SD:13.23%, Range 47.62%-91.67%). Among all the required reporting items, characterizing heterogeneity (score rate = 4.17%) was the least satisfied item. Among six parts of CHEERS, results part scored least at 0.55 (score rate = 54.79%) because of the incompleteness of characterizing uncertainty. Results from the Kruskal-Wallis test and Mann-Whitney U test showed that model choice, journal type, type of economic evaluations, and study perspective were associated with the reporting quality of the studies. CONCLUSIONS: There remains room to improve the reporting quality of economic evaluations for GLDs in NRDL. Checklists such as CHEERS should be widely used to improve the reporting quality of economic researches in China.
Assuntos
Hipoglicemiantes, China, Humanos, Hipoglicemiantes/economia, Hipoglicemiantes/uso terapêutico, Análise Custo-Benefício, Mecanismo de Reembolso/normas, NegociaçãoRESUMO
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
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
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-AIM: Flexible insulin therapy is currently considered the gold standard therapy of type 1 diabetes. We aimed to study the evolution of glycemic control, weight and nutritional intake of a group of patients with type 1 diabetes, three months after the initiation of functional insulin therapy (FIT). METHODS: This was a prospective longitudinal study having included 30 type 1 diabetic patients hospitalized for education to FIT. Each patient underwent an assessment of glycemic control (glycated hemoglobin (A1C) and number of hypoglycemia), weight and nutritional intake before FIT and 3 months after the initiation of this educative approach. RESULTS: The mean age of patients was 21,8 ± 7,9 years and the sex ratio was 0,5. The mean duration of diabetes was 7,2 ± 6 years. Three months after initiation of FIT, we observed a significant lowering of A1C, which went from 9,2 ± 1,6% to 8,3 ± 1,4% (p<0,001) of the number of minor hypoglycemia (p=0,001) and that of severe hypoglycemia (p= 0,021). the average weight went from 64,6 ± 13,1 kg to 65,5 ± 13,5 kg (p = 0,040) with a significant increase in BMI (p = 0,041). Weight gain was observed in 67% of patients. This weight gain contrasted with a significant decrease in caloric (p = 0,040) and in carbohydrates intakes (p = 0,027). CONCLUSION: Weight gain, associated with better glycemic control, should encourage the healthcare team to strengthen therapeutic education of patients undergoing FIT in order to limit weight gain.
Assuntos
Peso Corporal, Diabetes Mellitus Tipo 1, Hipoglicemiantes, Insulina, Humanos, Diabetes Mellitus Tipo 1/tratamento farmacológico, Diabetes Mellitus Tipo 1/sangue, Feminino, Masculino, Insulina/administração & dosagem, Insulina/uso terapêutico, Adulto, Adulto Jovem, Estudos Prospectivos, Estudos Longitudinais, Adolescente, Hipoglicemiantes/administração & dosagem, Hipoglicemiantes/uso terapêutico, Peso Corporal/fisiologia, Hemoglobinas Glicadas/análise, Hemoglobinas Glicadas/metabolismo, Hipoglicemia/prevenção & controle, Hipoglicemia/induzido quimicamente, Hipoglicemia/epidemiologia, Controle Glicêmico/métodos, Ingestão de Energia, Aumento de Peso/fisiologia, Aumento de Peso/efeitos dos fármacos, Fatores de Tempo, Glicemia/análise, Glicemia/metabolismoRESUMO
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
"Ganghwal" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that Ostericum koreanum extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.
Assuntos
Células 3T3-L1, Adipócitos, Adipogenia, Fármacos Antiobesidade, Hipoglicemiantes, PPAR gama, Extratos Vegetais, Camundongos, Extratos Vegetais/farmacologia, Extratos Vegetais/química, Animais, Hipoglicemiantes/farmacologia, Hipoglicemiantes/uso terapêutico, Adipogenia/efeitos dos fármacos, Adipócitos/efeitos dos fármacos, Adipócitos/metabolismo, PPAR gama/metabolismo, PPAR gama/genética, Fármacos Antiobesidade/farmacologia, Obesidade/tratamento farmacológico, Obesidade/metabolismo, Transportador de Glucose Tipo 4/metabolismo, Transportador de Glucose Tipo 4/genética, Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo, Proteína alfa Estimuladora de Ligação a CCAAT/genética, alfa-Glucosidases/metabolismo, Proteínas Quinases Ativadas por AMP/metabolismo, Antioxidantes/farmacologia, Inibidores de Glicosídeo Hidrolases/farmacologia, Crassulaceae/química, Metabolismo dos Lipídeos/efeitos dos fármacos, Diferenciação Celular/efeitos dos fármacosRESUMO
BACKGROUND: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. METHODS: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. DISCUSSION: The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov with identification number NCT05803473 on March 27th 2023.
Assuntos
Automonitorização da Glicemia, Glicemia, Diabetes Mellitus Tipo 2, Humanos, Diabetes Mellitus Tipo 2/diagnóstico, Diabetes Mellitus Tipo 2/sangue, Glicemia/análise, Automonitorização da Glicemia/métodos, Estudos Prospectivos, Testes Imediatos, Feminino, Masculino, Hospitalização, Insulina/uso terapêutico, Insulina/administração & dosagem, Hipoglicemiantes/uso terapêutico, Equipe de Assistência ao Paciente, Adulto, Pessoa de Meia-Idade, Monitoramento Contínuo da GlicoseRESUMO
BACKGROUND: Type 2 diabetes mellitus (DM) remains the most common type of DM and is associat-ed with disabling complications, reduced quality of life and reduced life expectancy. Satisfactory control of carbohydrate metabolism remains the key way to manage them. AIM: To perform a retrospective analysis of carbohydrate metabolism (in terms of glycated hemoglobin - HbA1c), the prevalence of complications, and features of hypoglycemic and concomitant therapy in patients with type 2 DM. MATERIALS AND METHODS: The analysis of sex and age characteristics, achieved level of HbA1c, diabetes complications, sugar-reducing and concomitant therapy according to the data of outpatient records of the patients who are on dispensary registration with an endocrinologist in the Endocrinology Department of the Consultative and Diagnostic Polyclinic of the Tomsk Regional Clinical Hospital in Tomsk was carried out. RESULTS: 546 outpatient medical records of patients with type 2 DM were analysed, among which there were 39.6% men (n=216) with a history of type 2 DM 8.0 years [3.0; 13.0] , median age 64.0 years [54.5; 71.0] and 60.4% women (n=330), history of type 2 DM 10.0 years [5.0; 15.0], median age 70.0 years [63.0; 75.0]. The achieved HbA1c level in men was 7.6% [6.3; 9.0] and in women 7.4% [6.4; 9.1]. 19.4% of men and 13.6% of women had an aggravated history of type 2 DM. According to the history, 6.5% of men (n=14) and 3% of women (n=10) with type 2 DM had a history of stroke, and myocardial infarction 12% (n=26) and 1.5% (n=5), respectively. Among the analysed outpatient records of type 2 DM patients, 18.5% of men (n=40) and 12.4% of women (n=41) were found to have diabetic nephropathy. Diabetic retinopathy was reported in 9.3% (n=20) of men and 4.2% (n=14) of women. Diabetic macroangiopathies were detected in 29.6% (n=64) of males and 9.7% (n=32) of females. Among other chronic complications of DM, diabetic neuroosteoarthropathy was recorded in 1% (n=2) of males and 3% (n=10) of females, diabetic polyneuropathy in 25% (n=54) and 21.5% (n=71), respectively. Diabetic foot was diagnosed in 1.9% (n=4) of men and 1.8% (n=6) of women. Among comorbid pathology, obesity was diagnosed in 45.4% (n=88) of men and 69.1% (n=228) of women, dyslipidaemia in 10.2% (n=22) and 10.6% (n=35) respectively, hypertension in 39.8% (n=86) and 32.6% (n=108) of cases. The diagnosis of non-alcoholic fatty liver disease was verified in 3.7% of men (n=7) and 1.8% of women (n=6), chronic heart failure in 7.4% of men (n=16) and 2.4% of women (n=8) registered for type 2 DM. According to the analysed outpatient records, 4.1% (n=23) of patients received diet therapy, 48.3% (n=263) received monotherapy and 47.6% (n=260) received combination therapy for type 2 DM. Metformin was the most commonly used monotherapy for type 2 DM 36.1% (n=197), followed by insulin 6.9% (n=38), sulfonylurea derivatives - 2.7% (n=15). Combination of metformin and dipeptidyl peptidase-4 inhibitors (13.9%) was the most commonly used combination therapy. CONCLUSION: Analysis of the current situation in the diabetology service will help to identify weaknesses and strengths, which is necessary to optimise existing therapeutic approaches in accordance with current clinical recommendations.
Assuntos
Diabetes Mellitus Tipo 2, Hemoglobinas Glicadas, Hipoglicemiantes, Humanos, Diabetes Mellitus Tipo 2/tratamento farmacológico, Diabetes Mellitus Tipo 2/epidemiologia, Masculino, Feminino, Pessoa de Meia-Idade, Hipoglicemiantes/uso terapêutico, Idoso, Estudos Retrospectivos, Hemoglobinas Glicadas/análise, Hemoglobinas Glicadas/metabolismo, Pacientes Ambulatoriais/estatística & dados numéricos, Federação Russa/epidemiologia, Complicações do Diabetes/epidemiologiaRESUMO
Memory issues are a prevalent symptom in different neurodegenerative diseases and can also manifest in certain psychiatric conditions. Despite limited medications approved for treating memory problems, research suggests a lack of sufficient options in the market. Studies indicate that a significant percentage of elderly individuals experience various forms of memory disorders. Metformin, commonly prescribed for type 2 diabetes, has shown neuroprotective properties through diverse mechanisms. This study explores the potential of metformin in addressing memory impairments. The current research gathered its data by conducting an extensive search across electronic databases including PubMed, Web of Science, Scopus, and Google Scholar. Previous research suggests that metformin enhances brain cell survival and memory function in both animal and clinical models by reducing oxidative stress, inflammation, and cell death while increasing beneficial neurotrophic factors. The findings of the research revealed that metformin is an effective medication for enhancing various types of memory problems in numerous studies. Given the rising incidence of memory disorders, it is plausible to utilize metformin, which is an affordable and accessible drug. It is often recommended as a treatment to boost memory.
Assuntos
Transtornos da Memória, Metformina, Metformina/uso terapêutico, Metformina/farmacologia, Transtornos da Memória/tratamento farmacológico, Humanos, Animais, Estresse Oxidativo/efeitos dos fármacos, Fármacos Neuroprotetores/uso terapêutico, Fármacos Neuroprotetores/farmacologia, Memória/efeitos dos fármacos, Hipoglicemiantes/farmacologia, Hipoglicemiantes/uso terapêutico, Encéfalo/efeitos dos fármacos, Encéfalo/metabolismoRESUMO
OBJECTIVE: To provide an online interactive decision aid to facilitate shared decision making in the context of medication choices for patients with type 2 diabetes mellitus (T2DM). SOURCES OF INFORMATION: The best available clinical prediction model for patients with T2DM was selected based on a review of guidelines, DynaMed, and UpToDate and a search of PubMed. A list of pharmacotherapeutic options for T2DM was compiled based on a review of guidelines, narrative reviews, and expert opinion. To determine the benefits and harms of each treatment, federated search engines were searched for meta-analyses of randomized controlled trials, supplemented by individual randomized controlled trials for outcomes not reported in meta-analyses. MAIN MESSAGE: Approximately 2.1 million Canadians have T2DM, with a resulting increased risk of death, cardiovascular disease, and microvascular outcomes. While more than a dozen medication options are available, decisions regarding these medications are challenging, as patients vary in their preferences. Shared decision making has the potential to individualize these difficult decisions, but the number of diabetes-related outcomes and available treatment options have made this historically impractical. It is within this context that the PEER Diabetes Medication Decision Aid was developed. This decision aid provides patients with personalized 10-year risk estimates for 6 clinically important diabetes-related outcomes. The tool also allows patients to focus on the outcome that matters most to them and to compare the benefits and harms of up to 12 different treatment options. This information is displayed in personalized absolute numbers, along with practical considerations such as cost. CONCLUSION: The PEER Diabetes Medication Decision Aid provides a practical tool that can enable patients with T2DM to come to autonomous and well-informed medication decisions.
