RESUMO
The 8th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Kidney, and Glycemic Outcomes was held virtually on November 10-12, 2022. Following the tradition of previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed outcomes trials as well as key trials important to the cardiovascular (CV) field. This year's focus was on the results of the DELIVER, EMPA-KIDNEY and SURMOUNT-1 trials and their implications for the treatment of heart failure (HF) and chronic kidney disease (CKD) with sodium-glucose cotransporter-2 (SGLT2) inhibitors and obesity with glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonists. A broad audience of primary care physicians, diabetologists, endocrinologists, cardiologists, and nephrologists participated online in discussions on new consensus recommendations and guideline updates on type 2 diabetes (T2D) and CKD management, overcoming clinical inertia, glycemic markers, continuous glucose monitoring (CGM), novel insulin preparations, combination therapy, and reclassification of T2D. The impact of cardiovascular outcomes on the design of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) trials, as well as the impact of real-world evidence (RWE) studies on the confirmation of CVOT outcomes and clinical trial design, were also intensively discussed. The 9th Cardiovascular Outcome Trial Summit will be held virtually on November 23-24, 2023 ( http://www.cvot.org ).
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Humanos , Glicemia , Automonitorização da Glicemia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Rim , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologiaRESUMO
These preliminary data from an ongoing first-in-human phase 1/2, open-label study provide proof-of-concept that pluripotent stem cell-derived pancreatic endoderm cells (PEC-01) engrafted in type 1 diabetes patients become islet cells releasing insulin in a physiologically regulated fashion. In this study of 17 subjects aged 22-57 with type 1 diabetes, PEC-01 cells were implanted subcutaneously in VC-02 macroencapsulation devices, allowing for direct vascularization of the cells. Engraftment and insulin expression were observed in 63% of VC-02 units explanted from subjects at 3-12 months post-implant. Six of 17 subjects (35.3%) demonstrated positive C-peptide as early as 6 months post-implant. Most reported adverse events were related to surgical implant or explant procedures (27.9%) or to side-effects of immunosuppression (33.7%). Initial data suggest that pluripotent stem cells, which can be propagated to the desired biomass and differentiated into pancreatic islet-like tissue, may offer a scalable, renewable alternative to pancreatic islet transplants.
Assuntos
Peptídeo C/metabolismo , Células Imobilizadas/citologia , Diabetes Mellitus Tipo 1/terapia , Endoderma/citologia , Insulina/metabolismo , Pâncreas/citologia , Transplante de Células-Tronco , Células-Tronco/citologia , Adolescente , Adulto , Idoso , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
AIMS: To use electronic health record data from real-world clinical practice to assess demographics, clinical characteristics and disease burden of adults with type 1 diabetes (T1D) in the United States. MATERIALS AND METHODS: Retrospective observational study of adults with T1D for ≥24 months at their first visit with a T1D diagnosis code ("index date") between July 2014 and June 2016 in the Optum Humedica database. Demographic characteristics, acute complications (severe hypoglycaemia [SH], diabetic ketoacidosis [DKA]), microvascular complications, cardiovascular (CV) events and health care resource utilization during the 12 months before the index date ("baseline period") were compared between patients with optimal versus suboptimal glycaemic control (glycated haemoglobin [HbA1c] <7.0% vs. ≥7.0% [53 mmol/mol]) at the closest measurement to the index date. RESULTS: Of 31 430 adults with T1D, 79.9% had suboptimal glycaemic control (mean HbA1c 8.8% [73 mmol/mol]). These patients were more likely to be younger, African American, uninsured or on Medicaid, obese, smokers, have uncontrolled hypertension and have depression. Despite worse glycaemic control and increased CV risk factors of uncontrolled hypertension, obesity and smoking, rates of coronary heart disease and stroke were not higher in these patients. Patients with suboptimal glycaemic control also experienced more diabetes complications (including SH, DKA and microvascular disease) and utilized more emergency care, with more emergency department visits and inpatient stays. CONCLUSION: This real-world study of >30 000 adults with T1D showed that individuals with suboptimal versus optimal glycaemic control differed significantly in terms of health care coverage, comorbidities, diabetes-related complications, health care utilization and CV risk factors. However, suboptimal control was not associated with increased risk of CV outcomes.
Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Adulto , Glicemia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/terapia , Registros Eletrônicos de Saúde , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/epidemiologia , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Estados Unidos/epidemiologiaRESUMO
Many individuals with type 2 diabetes (T2D) will eventually require insulin therapy to help achieve and maintain adequate glycemic control. However, the use of insulin can be associated with adverse effects such as hypoglycemia and weight gain, and in some patients the addition of insulin to treatment regimens is often still insufficient to achieve target glycemic control. Combining basal insulin with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of patients with T2D has been demonstrated to be effective and well tolerated, while mitigating many of the adverse events associated with giving either of these drug classes alone. Two titratable, fixed-ratio combination therapies, iGlarLixi and IDegLira, that combine basal insulin and a GLP-1 RA in a once-daily subcutaneous injection are currently approved by the US Food and Drug Administration (FDA) for the treatment of patients with T2D. The fixed-ratio combination iGlarLixi combines insulin glargine 100 Units/mL with lixisenatide, while IDegLira combines insulin degludec 100 Units/mL with liraglutide. While these new fixed-ratio combinations contain antihyperglycemic medications that are familiar to most health care providers, there are many questions relating to their use when formulated as a fixed-ratio combination therapy. This article discusses the 'top 10' considerations that health care providers should know about these novel combination therapies as these agents begin to gain an increasing presence in clinical practice.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Insulina Glargina/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Liraglutida/uso terapêutico , Peptídeos/uso terapêutico , Combinação de Medicamentos , Humanos , Hipoglicemia/induzido quimicamente , Insulina/uso terapêutico , Seleção de Pacientes , Aumento de PesoRESUMO
Previous cross-sectional analyses demonstrated that CD8(+) and CD4(+) T-cell reactivity to islet-specific antigens was more prevalent in T1D subjects than in healthy donors (HD). Here, we examined T1D-associated epitope-specific CD4(+) T-cell cytokine production and autoreactive CD8(+) T-cell frequency on a monthly basis for one year in 10 HD, 33 subjects with T1D, and 15 subjects with T2D. Autoreactive CD4(+) T-cells from both T1D and T2D subjects produced more IFN-γ when stimulated than cells from HD. In contrast, higher frequencies of islet antigen-specific CD8(+) T-cells were detected only in T1D. These observations support the hypothesis that general beta-cell stress drives autoreactive CD4(+) T-cell activity while islet over-expression of MHC class I commonly seen in T1D mediates amplification of CD8(+) T-cells and more rapid beta-cell loss. In conclusion, CD4(+) T-cell autoreactivity appears to be present in both T1D and T2D while autoreactive CD8(+) T-cells are unique to T1D. Thus, autoreactive CD8(+) cells may serve as a more T1D-specific biomarker.
Assuntos
Autoantígenos/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/imunologia , Ilhotas Pancreáticas/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Estudos de Casos e Controles , Citotoxicidade Imunológica , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , ELISPOT , Feminino , Humanos , Interferon gama/biossíntese , Ilhotas Pancreáticas/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
Despite years of research in the field of type 1 diabetes, patients with the disease remain without a therapeutic agent that can alter the underlying immune response in a clinically beneficial way. Glucagon-like peptide 1 agonist therapies have shown some promising effects in terms of positively affecting overall beta cell health and increasing beta cell mass, primarily in mouse models. The three agents of this class currently available for patients with type 2 diabetes have shown beneficial clinical effects on glucose control in this patient population. The purpose of this article is to review the preclinical and clinical data of these agents to date with a focus on the potential immunological and clinical benefits these drugs may have on patients with type 1 diabetes.