Podobnik Juliana, Prentice Kacey J
Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Diabetes Obes Metab. 2025 Mar;27(3):1032-1044. doi: 10.1111/dom.16154. Epub 2025 Jan 6.
Type 1 diabetes (T1D) is classically characterized as an autoimmune disease wherein the immune system erroneously attacks insulin-producing pancreatic β-cells, causing insulin insufficiency and severe metabolic dysregulation. However, intensive investigation and numerous clinical trials with immunotherapies have been largely unable to significantly alter the course of disease. Currently, there is no effective way to prevent or cure T1D, and insulin remains the cornerstone of T1D treatment. In recent years, a growing body of research suggests that β-cells actively contribute to the immune response and to disease development. Factors including glucotoxicity, lipotoxicity, inflammation, endoplasmic reticulum (ER) and oxidative stress can induce β-cell apoptosis and senescence, further promoting insulitis. Recent studies highlight the importance of targeting metabolic control for T1D management and treatment. Metabolic interventions, through their direct and indirect impacts on β-cells, have shown promise in preserving β-cell function. These interventions can reduce glucose toxicity, alleviate oxidative stress and inflammation, enhance insulin sensitivity, and indirectly mitigate the autoimmune responses. By preserving β-cell function, individuals with T1D attain better glycaemic control, reduced complication risks and exhibit improved overall metabolic health. Here, we provide an overview of insights from clinical studies, systematic reviews and meta-analyses that collectively demonstrate that adjunctive metabolic interventions can enhance glycaemic control, reduce insulin requirements and mitigate adverse effects associated with insulin monotherapy. They also show potential for halting disease progression, preserving residual β-cell function and improving long-term outcomes for newly diagnosed individuals. Future research should focus on optimizing these treatment strategies and establishing their long-term efficacy and safety.
1型糖尿病（T1D）的典型特征是一种自身免疫性疾病，即免疫系统错误地攻击产生胰岛素的胰腺β细胞，导致胰岛素分泌不足和严重的代谢失调。然而，深入的研究和众多免疫疗法的临床试验在很大程度上未能显著改变疾病进程。目前，尚无有效的方法预防或治愈T1D，胰岛素仍然是T1D治疗的基石。近年来，越来越多的研究表明，β细胞在免疫反应和疾病发展中发挥着积极作用。包括糖毒性、脂毒性、炎症、内质网（ER）和氧化应激等因素可诱导β细胞凋亡和衰老，进一步促进胰岛炎。最近的研究强调了针对代谢控制进行T1D管理和治疗的重要性。代谢干预通过对β细胞的直接和间接影响，在保护β细胞功能方面显示出前景。这些干预措施可以降低葡萄糖毒性，减轻氧化应激和炎症，提高胰岛素敏感性，并间接减轻自身免疫反应。通过保护β细胞功能，T1D患者能够实现更好的血糖控制，降低并发症风险，并展现出整体代谢健康状况的改善。在此，我们概述了临床研究、系统评价和荟萃分析的见解，这些研究共同表明，辅助性代谢干预可以增强血糖控制，减少胰岛素需求，并减轻与胰岛素单药治疗相关的不良反应。它们还显示出有潜力阻止疾病进展，保护残余β细胞功能，并改善新诊断患者的长期预后。未来的研究应侧重于优化这些治疗策略，并确定其长期疗效和安全性。
