Dataset Information

Type 1 diabetes mellitus and its oral tolerance therapy.

ABSTRACT: As a T cell-mediated autoimmune disease, type 1 diabetes mellitus (T1DM) is marked by insulin defect resulting from the destruction of pancreatic ?-cells. The understanding of various aspects of T1DM, such as its epidemiology, pathobiology, pathogenesis, clinical manifestations, and complications, has been greatly promoted by valuable research performed during the past decades. However, these findings have not been translated into an effective treatment. The ideal treatment should safely repair the destroyed immune balance in a long-lasting manner, preventing or stopping the destruction of ?-cells. As a type of immune hypo-responsiveness to the orally administrated antigen, oral tolerance may be induced by enhancement of regulatory T cells (Tregs) or by anergy/deletion of T cells, depending on the dosage of orally administrated antigen. Acting as an antigen-specific immunotherapy, oral tolerance therapy for T1DM has been mainly performed using animal models and some clinical trials have been completed or are still ongoing. Based on the review of the proposed mechanism of the development of T1DM and oral tolerance, we give a current overview of oral tolerance therapy for T1DM conducted in both animal models and clinical trials.

SUBMITTER: Mao RF

PROVIDER: S-EPMC7582116 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Type 1 diabetes mellitus and its oral tolerance therapy.

Mao Rui-Feng RF Chen Ying-Ying YY Zhang Ji J Chang Xin X Wang Ye-Fu YF

World journal of diabetes 20201001 10

As a T cell-mediated autoimmune disease, type 1 diabetes mellitus (T1DM) is marked by insulin defect resulting from the destruction of pancreatic β-cells. The understanding of various aspects of T1DM, such as its epidemiology, pathobiology, pathogenesis, clinical manifestations, and complications, has been greatly promoted by valuable research performed during the past decades. However, these findings have not been translated into an effective treatment. The ideal treatment should safely repair ...[more]

PMID: 33133388

Similar Datasets

Project description:IntroductionPrevious research has demonstrated a correlation among patient preferences, dosing burden, and medication nonadherence, a well-recognized challenge in type 2 diabetes mellitus (T2DM). The objective of this study was to elicit preferences for alternative dosing regimens for oral antihyperglycemic therapies among patients with T2DM and to quantify differences in dosing preferences among patients with different characteristics.MethodsPreferences for dosing of oral antihyperglycemic drugs (OAD) were evaluated by surveying patients with T2DM in the United States (US). Survey participants were adult US patients with T2DM who were taking no or only 1 OAD and no injectable therapies. Each patient completed a web-enabled discrete-choice experiment (DCE) including a series of 8 pairs of hypothetical OAD profiles. Each profile was defined by reductions in average glucose, dosing schedule (e.g., once-weekly, once-daily, or twice-daily dosing), chance of mild-to-moderate gastrointestinal side effects, frequency of hypoglycemia, weight change, incremental risk of congestive heart failure, and cost. Each participant also answered a direct question about dosing preference. Random-parameters logit was used to analyze the DCE data. Prespecified subgroups were analyzed.ResultsOf 2,262 patients invited to participate, 923 were included in the analysis (mean age 63 years, 45% male, 79% white). Reducing dosing frequency was statistically significantly important to patients; however, it was relatively less important than medication cost or clinical outcomes. On average, patients preferred once-weekly to once-daily dosing. Patients not currently taking an OAD had a stronger preference for once-weekly dosing than patients on treatment (P = 0.012). Patients younger than 45 years had a stronger preference for weekly dosing than older patients (P < 0.075).ConclusionsFor younger patients and patients not currently on treatment, once-weekly dosing may provide additional incentive to initiate and adhere to antihyperglycemic treatment; however, additional research will be required to confirm this hypothesis.

Project description:Diabetes mellitus (DM) is a chronic progressive metabolic disease that involves uncontrolled elevation of blood glucose levels. Among various therapeutic approaches, GLP-1 prevents type 2 diabetes mellitus (T2DM) patients from experiencing hyperglycemic episodes. However, the short half-life (<?5 min) and rapid clearance of GLP-1 often limits its therapeutic use. Here, we developed an oral GLP-1 gene delivery system to achieve an extended antidiabetic effect.Human IgG1 (hIgG1)-Fc-Arg/pDNA complexes were prepared by an electrostatic complexation of the expression plasmid with various ratios of the positively modified Fc fragments of an antibody (hIgG1-Fc-Arg) having a targeting ability to FcRn receptor. The shape and size of the complexes were examined by atomic force and field emission electron microscope. The stability of the complexes was tested in simulated gastrointestinal pH and physiological serum condition. Cellular uptake, transport, and toxicity of the complexes were tested in the Caco-2 cells. Biodistribution and antidiabetic effect of the complexes were observed in either Balb/c mice or Lepdb/db mice.A 50/1 ratio of the hIgG1-Fc-Arg/pDNA produced a complex structure having approximately 40 ~?60 nm size and also demonstrated protection of pDNA in the complex from the physiological pH and serum conditions. Cellular uptake and transport of the complex were demonstrated in Caco-2 cells having FcRn receptor expression and forming the monolayer-polarized structure. The cellular toxicity of both delivery vehicle and the complex revealed their minimal toxicity comparable with nontoxicity of a commercial transfection reagent. Biodistribution of the complex showed the detectable distribution of the complex in the most parts of gastrointestinal tract due to ubiquitous expression of the FcRn receptors. An in vivo type 2 diabetes treatment study of oral administration of hIgG1-Fc-9Arg/pGLP-1 complexes showed absorption and expression in GI tract of either Balb/c mice or Lepdb/db mice.In this study, we developed an oral GLP-1 gene delivery system on the platform of cationic hIgG1-Fc-9Arg. Prolonged t1/2, less immunoactivity, and better bioactivities of hIgG-Fc-9Arg/pGLP-1 complexes appeared to be a promising approach to achieve potent treatment of type 2 diabetes treatment.

Project description:OBJECTIVE:To update clinicians with an overview of empagliflozin for the treatment of type 2 diabetes mellitus (T2DM), with focus on use in combination regimens. METHODS:Keyword searches were conducted in the Medline database to identify literature reporting clinical trials of at least 12 weeks' duration using empagliflozin treatment in patients with T2DM. RESULTS:When given as monotherapy or in combination therapy (as add-on or single-pill therapy) with metformin, pioglitazone, sulfonylurea, linagliptin, and insulin, empagliflozin produced clinically meaningful reductions in glycated hemoglobin levels, plasma glucose concentrations, bodyweight, and blood pressure. These changes were sustained during long-term treatment. In a dedicated cardiovascular event trial, empagliflozin on top of standard of care demonstrated a significant reduction in the risk of cardiovascular mortality and all-cause mortality. Across the clinical trials, empagliflozin combination therapies were well tolerated, and empagliflozin used alone was not associated with increased risk of hypoglycemia versus placebo. Indeed, the combination of empagliflozin and metformin had a significantly reduced rate of hypoglycemia compared with the combination of metformin and a sulfonylurea. On the other hand, empagliflozin treatment did have increased risk of genital infections compared with placebo. In clinical trials to date, diabetic ketoacidosis was not seen more frequently with empagliflozin than with placebo, but physicians should be alert to the possibility of this rare event. CONCLUSION:Empagliflozin has the potential to make an important contribution to the treatment of patients with T2DM. In some patients, empagliflozin may be used as monotherapy, but it is most likely to be used in combination with other therapies. Given the reduced risk of mortality seen when empagliflozin was added to standard care in patients at high cardiovascular risk, as well as the lack of alternative options for patients at lower cardiovascular risk, empagliflozin may be added to ongoing regimens for a significant proportion of patients.

Dataset Information

Type 1 diabetes mellitus and its oral tolerance therapy.

Publications

Type 1 diabetes mellitus and its oral tolerance therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets