Type 1 diabetes: A new vision of the disease based on endotypes

Diabetes/Metabolism Research and Reviews, Journal Year: 2024, Volume and Issue: 40(2)

Published: Feb. 1, 2024

Abstract Diagnosis and management of type 1 diabetes (T1D) have remained largely unchanged for the last several years. The disease remains primarily focused on its phenotypical presentation less endotypes, namely specific biological mechanisms behind development disease. Furthermore, treatment T1D is essentially universal indiscriminate—with patients administering insulin at varying dosages frequencies to maintain adequate glycaemic control. However, it now well understood that a heterogeneous with many different (i.e. endotypes) complex pathophysiology. A range factors, including age onset, immune system regulation, rate β‐cell destruction, autoantibodies, body weight, genetics exposome are recognised play role in condition. Patients can be classified into distinct diabetic subtypes based these which used categorise endotypes. classification endotypes allows greater understanding natural progression disease, giving rise more accurate patient‐centred therapies follow‐up monitoring, specifically other autoimmune diseases. This review proposes 6 unique current literature. recognition could then direct therapeutic modalities patients' individual

Language: Английский

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Prevention and treatment of type 1 diabetes: in search of the ideal combination therapy targeting multiple immunometabolic pathways

Metabolism and Target Organ Damage, Journal Year: 2024, Volume and Issue: 4(3)

Published: May 16, 2024

Type 1 diabetes (T1D) represents an autoimmune disease caused by the gradual immune-mediated destruction of insulin-producing beta cells within pancreatic islets Langerhans, resulting in lifelong need for exogenous insulin therapy. According to recent estimates, T1D currently affects about 8.4 million individuals worldwide. Since a definitive biological cure this is not available yet, there great novel therapeutic strategies aimed at safely and effectively altering natural history during its sequential stages. Ideal goals include prevention beta-cell destruction, preservation residual mass endogenous secretion, replacement and/or regeneration cells, as well automated delivery through advanced closed-loop artificial pancreas systems. With regard, important research area focused on identification represented investigation immunotherapeutic beta-cell-protective agents used disease-modifying therapies forestall or eliminate dependence. In commentary, we discuss reasons why use combination targeting multiple immunometabolic dysfunctions associated with (other than autoimmunity) likely be more effective preserving cell function different stages T1D, compared single agents.

Language: Английский

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Dihydromyricetin as a Dietary Supplement Enhances Hypoglycemic Efficacy: Synergistic Modulation of the Gut-Liver with Sangzhi Alkaloids

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106197 - 106197

Published: Feb. 1, 2025

Language: Английский

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The partial clinical remission phase of type 1 diabetes: early-onset dyslipidemia, long-term complications, and disease-modifying therapies

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 16

Published: April 16, 2025

No therapy confers complete β-cell protection at any of the 3 stages type 1 diabetes (T1D). Disease-modifying therapies in aim to prolong preclinical (stages I and II) post-diagnostic partial clinical remission (PR) phases T1D reduce its short- long-term complications. These are focused on mitigating apoptosis by reducing autoimmune attacks surviving β-cells through several pathways; as well improving function enable production functional endogenous insulin C-peptide reduction proinsulin ratios other measures. target monotherapy or combination therapy. Stage is marked presence least one diabetes-associated autoantibody an individual with normoglycemia; stage II autoantibodies dysglycemia; III diagnosis antibodies, hyperglycemia, symptoms. Conventional thinking suggests that complications principally rooted early-stage hyperglycemia time disease, i.e., T1D. However, this theory hyperglycemic memory limited it does not address dichotomy lipid-based atherosclerotic cardiovascular disease (ASCVD) risk those Given current limitations developing disease-modifying because impact agents preservation, we introduce hyperlipidemic diabetes. This was developed author 2022 using same population article shortcomings explain ASCVD based PR history. In Review, presents new pathways for focus preventing early-phase dyslipidemia. It hoped including theoretical framework designing will help move field forward. supports hypothesis imprimatur rather than a process. hypothesizes pre-diagnostic interventions, T1D, ensure occurrence may be more effective long term III, PR. paradigm shift approach discussed review.

Language: Английский

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Saxagliptin/dapagliflozin is non‐inferior to insulin glargine in terms of β‐cell function in subjects with latent autoimmune diabetes in adults: A 12‐month, randomized, comparator‐controlled pilot study

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 26(5), P. 1670 - 1677

Published: Jan. 31, 2024

Abstract Aim To compare the efficacy and safety of saxagliptin/dapagliflozin insulin glargine in people with latent autoimmune diabetes adults (LADA). Methods In this phase 2b multicentre, open‐label, comparator‐controlled, parallel‐group, non‐inferiority study, we randomly assigned 33 LADA who had a fasting C‐peptide concentration ≥0.2 nmol/L (0.6 ng/mL) to receive 1‐year daily treatment either combination saxagliptin (5 mg) plus dapagliflozin (10 or (starting dose: 10 IU), both on top metformin. The primary outcome was 2‐h mixed meal‐stimulated area under curve (AUC), measured 12 months after randomization. Secondary outcomes were glycated haemoglobin (HbA1c) levels, change body mass index (BMI), hypoglycaemic events. Results modified intention‐to‐treat analysis, similar participants (median AUC: 152.0 ng*min/mL [95% confidence interval {CI} 68.2; 357.4] vs. 122.2 CI 84.3; 255.8]; p for noninferiority = 0.0087). Participants randomized lost more weight than those BMI at end study: −0.4 kg/m 2 −1.6; −0.3] +0.4 −0.3; +1.1]; 0.0076). No differences HbA1c number experiencing events found. Conclusions Saxagliptin/dapagliflozin non‐inferior terms β‐cell function 12‐month, small, enrolling still viable endogenous production. Weight loss greater saxagliptin/dapagliflozin, no glycaemic control risk.

Language: Английский

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A temperature-responsive dual-hormone foam nanoengine improves rectal absorptivity of insulin-pramlintide for diabetes treatment

Science Advances, Journal Year: 2024, Volume and Issue: 10(35)

Published: Aug. 28, 2024

Despite the therapeutic benefits of insulin-pramlintide dual-hormone therapy in diabetes, its application potential has been limited due to a lack efficient delivery routes. Here, we developed temperature-responsive foam nanoengine (HormFoam) and combined it with customized spraying device further construct an situ foam-generating system for improving rectal bioavailability therapy. To support rapid clinical translation, continuous microfluidic preparation HormFoam was proposed, including power unit perfluorocarbon nanodroplets pharmaceutical components Pluronic F127-functionalized liposomal insulin pramlintide. We found that could consistently generate foams drive drugs forward after administration, which enhanced intestinal distribution mucosa absorption, leading systemic codelivery insulin-pramlintide. reproduced physiology endocrine pancreas glycemic control induced body weight loss while reversing metabolic disorders diabetic mice good biosafety. Therefore, represents state-of-the-art regimen address unmet needs diabetes management.

Language: Английский

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Vitamin D Supplementation as a Therapeutic Strategy in Autoimmune Diabetes: Insights and Implications for LADA Management

Nutrients, Journal Year: 2024, Volume and Issue: 16(23), P. 4072 - 4072

Published: Nov. 27, 2024

Latent autoimmune diabetes of adults (LADA) is the most prevalent form (AI-D) in adulthood; however, its accurate diagnosis and optimal treatment remain challenging. Vitamin D deficiency (VDD) commonly observed LADA patients, while increased vitamin exposure through supplementation dietary intake associated with a reduced incidence LADA. Although limited, case reports, case-control studies, randomized clinical trials have examined effects supplementation—alone or combined dipeptidyl peptidase-4 inhibitors (DPP4-is)—on glucose regulation, residual β-cell function, glutamic acid decarboxylase antibody (GADA65) levels. Findings, preliminary, indicate that may enhance glycemic control, preserve reduce activity. Given accessibility, affordability, relative safety, presents an attractive adjunct option for patients. This narrative review discusses current evidence on potential therapeutic benefits patients AI-D, including LADA, who are also deficient. Beginning exploration epidemiological patterns, presentation, diagnostic framework essential understanding identifying this then examines proposed mechanisms which influence modulation pancreatic β-cells, integrating recent data pertinent to pathology. By distilling consolidating existing research, we aim provide platform advancing targeted investigations within distinct patient population.

Language: Английский

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The Potential Preventive and Therapeutic Role of Vitamin D in MS

Published: Jan. 1, 2024

Language: Английский

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The correlation between serum vitamin D status and the occurrence of diabetic foot ulcers: a comprehensive systematic review and meta‐analysis

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Sept. 20, 2024

Language: Английский

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Immunomodulatory agents and cell therapy for patients with type 1 diabetes

Archives of Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 68

Published: Jan. 1, 2024

Type 1 diabetes (TID) is a chronic disease caused by autoimmune destruction of pancreatic β-cells, that progresses in three stages: 1) stage 1: β-cell autoimmunity + normoglycemia; 2) 2: mild dysglycemia; 3) 3: symptomatic hyperglycemia. Interventions to prevent or cure T1D the various stages have been pursued and may target prevention β cells, regression insulitis, preservation recovery cells residual mass. Some therapies show promising results might change natural history approach patients with next few years. Teplizumab, humanized monoclonal antibody binds CD3, was recently approved USA delay Stage 3 individuals ≥ 8 years age. Other non-cellular immunomodulatory therapies, both antigen-specific non-specific, shown interesting either 2 recent onset T1D. Cell such as non-myeloablative transplantation autologous hematopoietic stem mesenchymal tolerogenic dendritic also studied these individuals, aiming immunomodulation. Stem cell-derived islet replacement therapy for long- standing T1D, especially asymptomatic hypoglycemia not resolved technology. This review aimed provide updated information on main agents cell options type diabetes.

Language: Английский

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