RESUMO
Background: No comprehensive meta-analysis has evaluated the efficacy and safety of ertugliflozin compared to a placebo in patients with Type 2 diabetes (T2D) until now. This meta-analysis fills this gap in knowledge. Methods: A systematic search was carried out in electronic databases to identify randomized controlled trials (RCTs) that included patients with T2D receiving ertugliflozin in the treatment group and placebo in the control group. The change in HbA1c from the baseline values was the primary outcome, whereas changes in plasma glucose and other metabolic parameters and adverse events (AEs), including hypoglycemia, were the secondary outcomes. Results: Seven RCTs involving 7283 subjects met the inclusion criteria. Ertugliflozin outperformed placebo in reducing HbA1c in both 5 mg (MD -0.62%, 95% CI [-0.80, -0.44], p < 0.00001, I 2 = 91%) and 15 mg (MD -0.69%, 95% CI [-0.91, -0.47], p < 0.00001, I 2 = 93%) doses. A higher proportion of patients achieved HbA1c < 7.0% with ertugliflozin than with placebo. Ertugliflozin was also superior to placebo in lowering fasting plasma glucose (FPG), body weight, and systolic and diastolic blood pressure (BP). Ertugliflozin and placebo had comparable AE profiles, including urinary tract infection (UTI) and hypoglycemia, except for the greater risk of genital mycotic infections (GMIs) with ertugliflozin. Ertugliflozin 5 and 15 mg have equivalent efficacy and safety profiles except for greater weight reduction with ertugliflozin 15 mg. Conclusion: Ertugliflozin has a good glycemic efficacy and a reassuring safety profile in managing T2D. Trial Registration: Registration number: CRD42023456450.
Assuntos
Glicemia , Compostos Bicíclicos Heterocíclicos com Pontes , Diabetes Mellitus Tipo 2 , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Resultado do Tratamento , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemia/induzido quimicamenteRESUMO
Background: Sulfonylureas have been a longstanding pharmacotherapy in the management of type 2 diabetes, with potential benefits beyond glycemic control. Although sulfonylureas are effective, interindividual variability exists in drug response. Pharmacometabolomics is a potent method for elucidating variations in individual drug response. Identifying unique metabolites associated with treatment response can improve our ability to predict outcomes and optimize treatment strategies for individual patients. Our objective is to identify metabolic signatures associated with good and poor response to sulfonylureas, which could enhance our capability to anticipate treatment outcome. Methods: In this cross-sectional study, clinical and metabolomics data for 137 patients with type 2 diabetes who are taking sulfonylurea as a monotherapy or a combination therapy were obtained from Qatar Biobank. Patients were empirically categorized according to their glycosylated hemoglobin levels into poor and good responders to sulfonylureas. To examine variations in metabolic signatures between the two distinct groups, we have employed orthogonal partial least squares discriminant analysis and linear models while correcting for demographic confounders and metformin usage. Results: Good responders showed increased levels of acylcholines, gamma glutamyl amino acids, sphingomyelins, methionine, and a novel metabolite 6-bromotryptophan. Conversely, poor responders showed increased levels of metabolites of glucose metabolism and branched chain amino acid metabolites. Conclusion: The results of this study have the potential to empower our knowledge of variability in patient response to sulfonylureas, and carry significant implications for advancing precision medicine in type 2 diabetes management.
Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Metabolômica , Compostos de Sulfonilureia , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Estudos Transversais , Compostos de Sulfonilureia/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Hipoglicemiantes/uso terapêutico , Idoso , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismoRESUMO
BACKGROUND: The first-line treatment for polycystic ovary syndrome (PCOS) is lifestyle modification. However, it is currently unknown whether digital medicine can assist patients with PCOS in maintaining a healthy lifestyle while alleviating PCOS symptoms. OBJECTIVE: This study aims to evaluate the efficacy of WeChat-based digital intervention versus metformin treatment in women with PCOS and insulin resistance. METHODS: A total of 80 women with PCOS and insulin resistance were recruited from an endocrinology clinic and randomly assigned to receive either a WeChat-based digital intervention (n=40, 50%) or metformin (n=40, 50%) for 12 weeks. The WeChat-based digital intervention consisted of 3 modules; a coach assisted the patients in using the intervention. The primary outcome was the change in a homeostatic model assessment for insulin resistance. At baseline and after the 12-week intervention, anthropometric parameters, menstruation frequency, sex hormone levels, metabolic factors, and body fat distribution were measured in the clinic. Furthermore, self-assessed web-based questionnaires on diet, exercise, sleep, anxiety, and depression were obtained. RESULTS: A total of 72 participants completed the follow-up (for a 90% follow-up rate), including 35 of 40 (88%) participants from the digital intervention group and 37 of 40 (93%) participants from the metformin group. The homeostatic model assessment for insulin resistance in the digital intervention group was significantly improved after 12 weeks of treatment with a mean change of -0.93 (95% CI -1.64 to -0.23), but no statistical difference was observed between the groups (least squares mean difference -0.20; 95% CI -0.98 to 0.58; P=.62). Both digital intervention and metformin treatment significantly improved menstruation frequency (digital intervention: P<.001; metformin: P<.001) and reduced body weight (digital intervention: P<.001; metformin: P<.001) and total fat mass (digital intervention: P<.001; metformin: P<.001). Furthermore, the digital intervention had a significant advantage over metformin in improving waist circumference (least squares mean difference -1.84; 95% CI -3.44 to -0.24; P=.03), waist-to-hip ratio (least squares mean difference -0.02; 95% CI -0.03 to 0.00; P=.03), total fat mass (least squares mean difference -1.59; 95% CI -2.88 to -0.30; P=.02), and dehydroepiandrosterone sulfate (least squares mean difference -69.73; 95% CI -129.70 to -9.75; P=.02). In terms of safety, the main adverse events were sensations of hunger in the digital intervention group (2/40, 5%) and gastrointestinal adverse events in the metformin group (12/40, 30%). CONCLUSIONS: Our data suggest that digital intervention is an effective treatment option for patients with PCOS, with an efficacy comparable to that of metformin, and that it can also alleviate the negative effects of medications and make it easier and more efficient to adhere to lifestyle treatments. WeChat-based digital interventions have the potential to provide a new path for the improvement and health of women with PCOS in China. TRIAL REGISTRATION: ClinicalTrials.gov NCT05386706; https://clinicaltrials.gov/study/NCT05386706.
Assuntos
Resistência à Insulina , Metformina , Síndrome do Ovário Policístico , Humanos , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/terapia , Feminino , Metformina/uso terapêutico , Adulto , Adulto Jovem , Hipoglicemiantes/uso terapêuticoRESUMO
AIMS: To examine longitudinal and dose-d ependent associations between dietary fiber intake and various clinical outcomes over 48 weeks of pharmacological treatment in T2DM patients. METHODS: In this secondary analysis, we used data from the MARCH trial, which was designed to compare the efficacy of acarbose or metformin monotherapy as the initial therapy in Chinese patients newly diagnosed with T2DM. Dietary data were obtained using a 24-h dietary recall method to evaluate the intakes of dietary fiber from different sources as well as the carbohydrate-to-fiber ratio. RESULTS: A total of 551 newly-diagnosed patients with T2DM complete dietary records (286 in the acarbose group and 265 in the metformin group) were included. Higher intake of total fiber and whole grain fiber was positively associated with better ß-cell function, insulin sensitivity and postprandial glycemic control under acarbose treatment. Higher intake of legume fiber was associated with better glycemic control under both acarbose and metformin treatment but with better weight loss only under metformin treatment. A high-carbohydrate-low-fiber diet was associated with worse glycemic control and lower HDL-C under acarbose treatment but with higher insulin sensitivity and better weight loss under metformin treatment. CONCLUSIONS: The notable effects of various dietary fibers when combined with different oral glucose-lowering medications should be considered to maximize therapeutic benefit.
Assuntos
Acarbose , Glicemia , Fatores de Risco Cardiometabólico , Diabetes Mellitus Tipo 2 , Fibras na Dieta , Hipoglicemiantes , Metformina , Redução de Peso , Humanos , Acarbose/uso terapêutico , Fibras na Dieta/administração & dosagem , Fibras na Dieta/uso terapêutico , Metformina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Redução de Peso/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Glicemia/análise , Glicemia/metabolismo , Estudos Longitudinais , Resistência à Insulina , Idoso , Controle Glicêmico/métodos , Adulto , ChinaRESUMO
BACKGROUND: Glucagon-like peptide-1 receptor agonists are a viable option for the prevention of Alzheimer's disease (AD) but the mechanisms of this potential disease modifying action are unclear. We investigated the effects of once-weekly exenatide (EQW) on AD associated proteomic clusters. METHODS: The Exenatide Study of Cardiovascular Event Lowering study compared the cardiovascular effects of EQW 2 mg with placebo in 13,752 people with type 2 diabetes mellitus. 4,979 proteins were measured (Somascan V0.4) on baseline and 1-year plasma samples of 3,973 participants. C-reactive protein (CRP), ficolin-2 (FCN2), plasminogen activator inhibitor 1 (PAI-1), soluble vascular cell adhesion protein 1 (sVCAM1) and 4 protein clusters were tested in multivariable mixed models. RESULTS: EQW affected FCN2 (Cohen's d -0.019), PAI-1 (Cohen's d -0.033), sVCAM-1 (Cohen's d 0.035) and a cytokine-cytokine cluster (Cohen's d 0.037) significantly compared with placebo. These effects were sustained in individuals over the age of 65 but not in those under 65. CONCLUSIONS: EQW treatment was associated with significant change in inflammatory proteins associated with AD. TRIAL REGISTRATION: EXSCEL is registered on ClinicalTrials.gov: NCT01144338 on 10th of June 2010.
Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Exenatida , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/sangue , Masculino , Feminino , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Exenatida/uso terapêutico , Pessoa de Meia-Idade , Hipoglicemiantes/uso terapêutico , Método Duplo-Cego , Inibidor 1 de Ativador de Plasminogênio/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Inflamação/tratamento farmacológicoRESUMO
Background: Older people with diabetes are at high risk for hypoglycemia. Implementing a hypoglycemia treatment protocol in long-term care (LTC) settings may positively affect patient-related outcomes and health care resource utilization and costs. Anecdotal experience indicates little has been studied and published regarding this clinical practice. Objective: To identify hypoglycemia treatment protocols established for LTC settings and assess their effects on patient-related outcomes and health care resource use. Data Sources: The authors performed a systematic literature search of English-language articles and abstracts published between January 1, 2003 (PubMed), or 2018 (Google Scholar) and May 10, 2023. Search terms were "hypoglycemia," "diabetes mellitus," "longterm care," "nursing facilities," "assisted living facilities," "geriatrics," "elderly," "aged," "disabled," "disease management," "evidence-based medicine," "clinical protocols," "guideline," "glucagon," and/or "blood glucose." Included were publications with hypoglycemia treatment and management protocols or hypoglycemia-specific recommendations for LTC settings. DATA SYNTHESIS: The authors identified 405 articles and abstracts, removed 36 duplicates, screened 369 titles/ abstracts, and analyzed the full text for 93. Five met the inclusion criteria. Two originated from the American Diabetes Association: 2016 position statement regarding the management of diabetes in LTC and skilled nursing facilities, and 2023 standard-of-care guideline for managing older people with diabetes. One included the results after implementing an overall diabetes clinical care management algorithm in LTC facilities. A 2020 abstract and 2019 article were the only 2 publications involving specific hypoglycemia treatment protocols in LTC settings. Conclusion: This systematic literature search identified lack of published hypoglycemia treatment protocols in LTC settings and their effects on patient outcomes.
Assuntos
Hipoglicemia , Assistência de Longa Duração , Humanos , Hipoglicemia/terapia , Idoso , Diabetes Mellitus/terapia , Protocolos Clínicos/normas , Glicemia/análise , Glicemia/metabolismo , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversosRESUMO
This report addresses evidence for efficacy of diabetes medications with a focus on stroke risk reduction. The cardiovascular benefits of SGLT-2 inhibitors and GLP-1 receptor agonists have been well-established; however, clinical trials to date have examined composite cardiovascular endpoints that include, but do not specifically focus on, stroke. The purpose of this case review is to examine the evidence for the various diabetes medications in reducing the risk for stroke. This literature review was inspired by a patient seen in a geriatric day hospital program with diabetes and a history of multiple strokes. Our goal was to select a diabetes management regimen that would provide both glycemic control and stroke risk reduction. As diabetes and cerebrovascular disease commonly coexist and are important contributors to morbidity and mortality in older individuals, appropriate management must incorporate both current evidence as well as consideration for patient-specific factors that may influence the treatment plan. This patient case illustrates the importance of both.
Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Prevenção Secundária , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/etiologia , Hipoglicemiantes/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Prevenção Secundária/métodos , Idoso de 80 Anos ou mais , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , FemininoRESUMO
Glucagon-like peptide-1 receptor (GLP-1R) agonist, a subgroup of incretin-based anti-diabetic therapies, is an emerging medication with benefits in reducing blood glucose and weight and increasing cardiovascular protection. Contrarily, concerns have been raised about GLP-1R agonists increasing the risk of particular cancers. Recently, several epidemiological studies reported contradictory findings of incretin-based therapy on the risk modification for cholangiocarcinoma (CCA). The first cohort study demonstrated that incretin-based therapy was associated with an increased risk of CCA. Later studies, however, showed a null effect of incretin-based therapy on CCA risk for dipeptidyl peptidase-4 inhibitor nor GLP-1R agonist. Mechanistically, glucagon-like peptide 1 receptor is multifunctional, including promoting cell growth. High GLP-1R expressions were associated with progressive phenotypes of CCA cells in vitro. Unexpectedly, the GLP-1R agonist showed anti-tumor effects on CCA cells in vitro and in vivo with unclear mechanisms. Our recent report also showed that GLP-1R agonists suppressed the expression of GLP-1R in CCA cells in vitro and in vivo, leading to the inhibition of CCA tumor growth. This editorial reviews recent evidence, discusses the potential effects of GLP-1R agonists in CCA patients, and proposes underlying mechanisms that would benefit from further basic and clinical investigation.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Receptor do Peptídeo Semelhante ao Glucagon 1 , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Incretinas/uso terapêutico , Incretinas/farmacologia , Proliferação de Células/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , AnimaisRESUMO
This editorial takes a deeper look at the insights provided by Soresi and Giannitrapani, which examined the therapeutic potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for metabolic dysfunction-associated fatty liver disease. We provide supplementary insights to their research, highlighting the broader systemic implications of GLP-1RAs, synthesizing the current understanding of their mechanisms and the trajectory of research in this field. GLP-1RAs are revolutionizing the treatment of type 2 diabetes mellitus and beyond. Beyond glycemic control, GLP-1RAs demonstrate cardiovascular and renal protective effects, offering potential in managing diabetic kidney disease al-ongside renin-angiotensin-aldosterone system inhibitors. Their role in bone metabolism hints at benefits for diabetic osteoporosis, while the neuroprotective properties of GLP-1RAs show promise in Alzheimer's disease treatment by modulating neuronal insulin signaling. Additionally, they improve hormonal and metabolic profiles in polycystic ovary syndrome. This editorial highlights the multifaceted mechanisms of GLP-1RAs, emphasizing the need for ongoing research to fully realize their therapeutic potential across a range of multisystemic diseases.
Assuntos
Diabetes Mellitus Tipo 2 , Receptor do Peptídeo Semelhante ao Glucagon 1 , Controle Glicêmico , Hipoglicemiantes , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Controle Glicêmico/métodos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonRESUMO
This cross-sectional study investigates the association between glucagon-like peptide-1 receptor agonists and food retention during esophagogastroduodenoscopy.
Assuntos
Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Hipoglicemiantes/uso terapêutico , Esvaziamento Gástrico/efeitos dos fármacos , Agonistas do Receptor do Peptídeo 1 Semelhante ao GlucagonRESUMO
CLINICAL QUESTION: What is the impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on survival and on cardiovascular and kidneyoutcomes for adults living with chronic kidney disease (CKD)? CURRENT PRACTICE: Few therapies slow kidney disease progression and improve long term prognosis for adults living with CKD. SGLT-2 inhibitors have demonstrated cardiovascular and kidney benefits in adults with CKD with and without type 2 diabetes. Existing guidance for SGLT-2 inhibitors does not account for the totality of current best evidence for adults with CKD and does not provide fully stratified treatment effects and recommendations across all risk groups based on risk of CKD progression and complications. RECOMMENDATIONS: The guideline panel considered evidence regarding benefits and harms of SGLT-2 inhibitor therapy for adults with CKD over a five year period, along with contextual factors, and provided the following recommendations:1. For adults at low risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)2. For adults at moderate risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)3. For adults at high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour)4. For adults at very high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour).Recommendations are applicable to all adults with CKD, irrespective of type 2 diabetes status. HOW THIS GUIDELINE WAS CREATED: An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified typical risk strata of adults with CKD (from low to very high risk of CKD progression and related complications) using the classification system developed by Kidney Disease Improving Global Outcomes (KDIGO), and applied an individual patient perspective in moving from evidence to recommendations. Effects of SGLT-2 inhibitors were interpreted in absolute terms applicable to different risk strata with varying baseline risks for outcomes of benefit over a five year period. The panel explicitly considered the balance of benefits, harms, and burdens of starting an SGLT-2 inhibitor, incorporating the values and preferences of adults with different risk profiles. Interactive evidence summaries and decision aids accompany multilayered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that allows reuse and adaptation. THE EVIDENCE: A linked systematic review and pairwise meta-analysis (13 trials including 29 614 participants) of benefits and harms associated with SGLT-2 inhibitors in adults with CKD with or without type 2 diabetes informed guidance. Among individuals at very high risk of CKD progression and complications, moderate to high certainty evidence shows SGLT-2 inhibitors (relative to placebo or standard care without SGLT-2 inhibitors) decrease all-cause and cardiovascular mortality, hospitalisation for heart failure, kidney failure, non-fatal myocardial infarction, and non-fatal stroke. Among individuals at high risk, moderate to high certainty evidence shows SGLT-2 inhibitors result in similar benefits across outcomes except demonstrating little or no effect on hospitalisation for heart failure and kidney failure. Among individuals at moderate and low risk, moderate to high certainty evidence shows SGLT-2 inhibitors probably reduce all-cause mortality and non-fatal stroke, with little or no effect for other outcomes of benefit. Risk-stratified estimates were unavailable for outcomes of harm; the panel therefore considered absolute effects summarised across risk strata. SGLT-2 inhibitors are associated with little or no effect on acute kidney injury requiring dialysis, bone fractures, lower limb amputations, ketoacidosis, genital infections, or symptomatic hypovolaemia, although a residual possibility of harms at the individual patient level remains. UNDERSTANDING THE RECOMMENDATION: In order to apply recommendations, clinicians must appropriately identify adults with CKD, consider the underlying aetiology, and risk stratify them based on glomerular filtration rate (estimated or measured) and degree of albuminuria. In addition to classifying individuals into risk strata, further estimation of a given patient's risk based on the extent of their kidney disease and other comorbidities may be warranted to inform individual-level decisions and shared decision making. Available risk calculators may help estimate a given patient's risk of CKD progression and complications.
Assuntos
Diabetes Mellitus Tipo 2 , Progressão da Doença , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Insuficiência Renal Crônica/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Adulto , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Doenças Cardiovasculares/prevenção & controleRESUMO
BACKGROUND: Type 2 diabetes prevalence is steadily increasing worldwide, and South Africa is one of the countries in Africa with the highest prevalence of this disease, along with other non-communicable diseases. The adherence to treatment in male patients with type 2 diabetes is influenced by their attitudes towards medication and how they perceive their condition. To some extent, these factors impact the treatment outcomes for patients undergoing type 2 diabetes treatment. The purpose of this study was to investigate the perceptions of male patients with type 2 diabetes on their adherence to diabetic therapy. The study was conducted in the clinics of the City of Tshwane Metropolitan municipality in Gauteng. METHODS: This study followed a qualitative, exploratory design. Data were gathered from 15 male patients who were purposefully sampled through in-person, one-on-one interviews with the principal investigator. The eight steps outlined by Tesch were used to analyse the participant data. RESULTS: Emergent themes indicated that there were barriers to adherence to diabetic treatment and also factors that promoted adherence to diabetic treatment among the participants. Several factors were found to affect treatment uptake among the participants. CONCLUSION: Patients demonstrated various reactions to diabetic treatment, highlighting the need for reinforcing education at the time of diagnosis and treatment initiation. Additionally, regular patient follow-up may be essential to improve adherence among patients.Contribution: The study highlights the importance of health promotion and the need to develop materials for medication-specific counselling for patients receiving diabetic treatment, in order to promote adherence.
Assuntos
Diabetes Mellitus Tipo 2 , Adesão à Medicação , Pesquisa Qualitativa , Humanos , Masculino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/psicologia , Pessoa de Meia-Idade , África do Sul/epidemiologia , Adesão à Medicação/psicologia , Idoso , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Hipoglicemiantes/uso terapêutico , Entrevistas como AssuntoRESUMO
Background and aims: To analyze the effect of oral metformin on changes in gut microbiota characteristics and metabolite composition in normal weight type 2 diabetic patients. Methods: T2DM patients in the cross-sectional study were given metformin for 12 weeks. Patients with unmedicated T2DM were used as a control group to observe the metrics of T2DM patients treated with metformin regimen. 16S rDNA high-throughput gene sequencing of fecal gut microbiota of the study subjects was performed by llumina NovaSeq6000 platform. Targeted macro-metabolomics was performed on 14 cases of each of the gut microbiota metabolites of the study subjects using UPLC-MS/MS technology. Correlations between the characteristics of the gut microbiota and its metabolites, basic human parameters, glycolipid metabolism indicators, and inflammatory factors were analyzed using spearman analysis. Results: Glycolipid metabolism indexes and inflammatory factors were higher in normal-weight T2DM patients than in the healthy population (P<0.05), but body weight, BMI, waist circumference, and inflammatory factor concentrations were lower in normal-weight T2DM patients than in obese T2DM patients (P<0.05). Treatment with metformin in T2DM patients improved glycolipid metabolism, but the recovery of glycolipid metabolism was more pronounced in obese T2DM patients. None of the differences in α-diversity indexes were statistically significant (P>0.05), and the differences in ß-diversity were statistically significant (P <0.05). Community diversity and species richness recovered after metformin intervention compared to before, and were closer to the healthy population. We found that Anaerostipes/Xylose/Ribulose/Xylulose may play an important role in the treatment of normal-weight T2DM with metformin by improving glycemic lipids and reducing inflammation. And Metformin may play a role in obese T2DM through Romboutsia, medium-chain fatty acids (octanoic acid, decanoic acid, and dodecanoic acid). Conclusion: Gut microbial dysbiosis and metabolic disorders were closely related to glucose-lipid metabolism and systemic inflammatory response in normal-weight T2DM patients. Metformin treatment improved glucose metabolism levels, systemic inflammation levels in T2DM patients, closer to the state of healthy population. This effect may be mediated by influencing the gut microbiota and microbial host co-metabolites, mainly associated with Anaerostipes and xylose/Ribulose/Xylulose. Metformin may exert its effects through different pathways in normal-weight versus obese T2DM patients.
Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hipoglicemiantes , Metformina , Humanos , Metformina/uso terapêutico , Metformina/farmacologia , Metformina/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Masculino , Feminino , Pessoa de Meia-Idade , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Estudos Transversais , Adulto , Administração Oral , Fezes/microbiologia , Fezes/químicaRESUMO
Many patients with diabetes struggle with post-meal high blood glucose due to missed or untimely meal-related insulin doses. To address this challenge, our research aims to: (1) study mealtime patterns in patients with type 1 diabetes using wearable insulin pump data, and (2) develop personalized models for predicting future mealtimes to support timely insulin dose administration. Using two independent datasets with over 45,000 meal logs from 82 patients with diabetes, we find that the majority of people ( â¼ 60%) have irregular and inconsistent mealtime patterns that change notably through the course of each day and across months in their own historical data. We also show the feasibility of predicting future mealtimes with personalized LSTM-based models that achieve an average F1 score of > 95% with less than 0.25 false positives per day. Our research lays the groundwork for developing a meal prediction system that can nudge patients with diabetes to administer bolus insulin doses before meal consumption to reduce the occurrence of post-meal high blood glucose.
Assuntos
Glicemia , Diabetes Mellitus Tipo 1 , Sistemas de Infusão de Insulina , Insulina , Refeições , Dispositivos Eletrônicos Vestíveis , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Insulina/administração & dosagem , Masculino , Feminino , Glicemia/análise , Adulto , Pessoa de Meia-Idade , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêuticoRESUMO
Cardiovascular-kidney-metabolic health reflects the interactions between metabolic risk factors, chronic kidney disease, and the cardiovascular system. A growing body of literature suggests that metabolic syndrome (MetS) in individuals of normal weight is associated with a high prevalence of cardiovascular diseases and an increased mortality. The aim of this study was to establish a non-invasive preclinical model of MetS in support of future research focusing on the effects of novel antidiabetic therapies beyond glucose reduction, independent of obesity. Eighteen healthy adult Beagle dogs were fed an isocaloric Western diet (WD) for ten weeks. Biospecimens were collected at baseline (BAS1) and after ten weeks of WD feeding (BAS2) for measurement of blood pressure (BP), serum chemistry, lipoprotein profiling, blood glucose, glucagon, insulin secretion, NT-proBNP, angiotensins, oxidative stress biomarkers, serum, urine, and fecal metabolomics. Differences between BAS1 and BAS2 were analyzed using non-parametric Wilcoxon signed-rank testing. The isocaloric WD model induced significant variations in several markers of MetS, including elevated BP, increased glucose concentrations, and reduced HDL-cholesterol. It also caused an increase in circulating NT-proBNP levels, a decrease in serum bicarbonate, and significant changes in general metabolism, lipids, and biogenic amines. Short-term, isocaloric feeding with a WD in dogs replicated key biological features of MetS while also causing low-grade metabolic acidosis and elevating natriuretic peptides. These findings support the use of the WD canine model for studying the metabolic effects of new antidiabetic therapies independent of obesity.
Assuntos
Modelos Animais de Doenças , Hipoglicemiantes , Síndrome Metabólica , Obesidade , Animais , Cães , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Glicemia/metabolismo , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Peptídeo Natriurético Encefálico/sangue , Peptídeo Natriurético Encefálico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , FemininoRESUMO
BACKGROUND: Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. METHODS: Before the 12-week intervention, all participants (n = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group (n = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants' glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. RESULTS: Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels (p = 0.0144), whereas no increase was observed in the non-IF group (p = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity (p < 0.0001, p = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 (p = 0.0455) and LCAT (p = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance. CONCLUSIONS: A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality. TRIAL REGISTRATION: The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070.
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Biomarcadores , Glicemia , Diabetes Mellitus Tipo 2 , Jejum , Obesidade , Fosfatidilcolina-Esterol O-Aciltransferase , Humanos , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Jejum/sangue , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Resultado do Tratamento , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/dietoterapia , Obesidade/fisiopatologia , Obesidade/terapia , Glicemia/metabolismo , Fatores de Tempo , Biomarcadores/sangue , Restrição Calórica , Arildialquilfosfatase/sangue , HDL-Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol/sangue , Redução de Peso , Idoso , Adulto , Dieta Saudável , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Jejum IntermitenteAssuntos
Receptor do Peptídeo Semelhante ao Glucagon 1 , Hipolipemiantes , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipolipemiantes/uso terapêutico , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controleRESUMO
BACKGROUND: Diabetes mellitus has emerged as a pressing global concern, with a notable increase in recent years. Despite advancements in treatment, existing medications struggle to halt the progression of diabetes and its associated complications. Increasing evidence underscores inflammation as a significant driver in the onset of diabetes mellitus. Therefore, perspectives on new therapies must consider shifting focus from metabolic stress to inflammation. High mobility group box (HMGB-1), a nuclear protein regulating gene expression, gained attention as an endogenous danger signal capable of sparking inflammatory responses upon release into the extracellular environment in the late 1990s. PURPOSE: Given the parallels between inflammatory responses and type 2 diabetes (T2D) development, this review paper explores HMGB-1's potential involvement in onset and progression of diabetes complications. Specifically, we will review and update the understanding of HMGB-1 and its inflammatory pathways in insulin resistance, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy. CONCLUSIONS: HMGB-1 and its receptors i.e. receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) present promising targets for antidiabetic interventions. Ongoing and future projects in this realm hold promise for innovative approaches targeting HMGB-1-mediated inflammation to ameliorate diabetes and its complications.
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Proteína HMGB1 , Hipoglicemiantes , Receptor para Produtos Finais de Glicação Avançada , Transdução de Sinais , Humanos , Proteína HMGB1/metabolismo , Proteína HMGB1/antagonistas & inibidores , Animais , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Hipoglicemiantes/uso terapêutico , Mediadores da Inflamação/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Anti-Inflamatórios/uso terapêutico , Terapia de Alvo Molecular , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Resistência à Insulina , Receptores Toll-Like/metabolismo , Retinopatia Diabética/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/etiologia , Retinopatia Diabética/prevenção & controle , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/tratamento farmacológico , Complicações do Diabetes/metabolismo , Complicações do Diabetes/tratamento farmacológicoRESUMO
AIMS: Glucagon-like peptide-1 receptor agonist (GLP-1RA) may promote bone formation, but conversely, they could also weaken bones due to the reduction in mechanical load associated with weight loss. However, the clinical effects in humans have not been clearly demonstrated. This meta-analysis aimed to evaluate whether GLP-1RAs affect BMD and bone turnover markers. MATERIAL AND METHODS: PubMed, Embase, and Scopus were searched on June 13, 2024. The eligibility criteria were: (1) human studies, (2) receiving a GLP-1RA for more than 4 weeks, (3) an untreated control group or a placebo group, (4) reporting of at least one BMD or bone turnover marker, and (5) an RCT design. The risk of bias was assessed using the Cochrane risk of bias 2 tool. Fixed- or random-effects meta-analysis was performed according to heterogeneity. RESULTS: Seven studies were included in the meta-analysis. GLP-1RAs did not significantly change BMD in the femoral neck (mean difference [MD], 0.01 g/cm2; 95% CI, -0.01-0.04 g/cm2), in the total hip (MD, -0.01 g/cm2; 95% CI, -0.02-0.01 g/cm2), and in the lumbar spine (MD, 0 g/cm2; 95% CI, -0.02-0.02 g/cm2). C-terminal telopeptide of type 1 collagen (CTX), a bone resorption marker, significantly increased after GLP-1RA treatment (MD, 0.04 µg/L; 95% CI, 0.01-0.07 µg/L). GLP-1RAs did not significantly change bone formation markers such as procollagen type 1 N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin. CONCLUSIONS: GLP-1RA did not affect BMD and bone formation markers. However, GLP-1RAs led to a significant increase in CTX.