Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece.
Athens University Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Obes Rev. 2021 Aug;22(8):e13231. doi: 10.1111/obr.13231. Epub 2021 Mar 8.
Efforts to unravel the pathophysiological mechanisms of type 2 diabetes (T2D) have been traditionally trapped into a metabolic perspective. However, T2D is a phenotypically and pathophysiologically heterogenous disorder, and the need for a tailored approach in its management is becoming increasingly evident. There is emerging evidence that irregular immune responses contribute to the development of hyperglycemia in T2D and, inversely, that insulin resistance is a component of the pathogenesis of autoimmune diabetes. Nevertheless, it has not yet been fully elucidated to what extent the presence of conventional autoimmune markers, such as autoantibodies, in subjects with T2D might affect the natural history of the disease and particularly each response to various treatments. The challenge for future research in the field is the discovery of novel genetic, molecular, or phenotypical indicators that would enable the characterization of specific subpopulations of people with T2D who would benefit most from the addition of immunomodulatory therapies to standard glucose-lowering treatment. This narrative review aims to discuss the plausible mechanisms through which the immune system might be implicated in the development of metabolic disturbances in T2D and obesity and explore a potential role of immunotherapy in the future management of the disorder and its complications.
传统上，人们一直试图从代谢角度来阐明 2 型糖尿病（T2D）的病理生理机制。然而，T2D 是一种表型和病理生理学上异质的疾病，其管理需要量身定制的方法，这一点变得越来越明显。有新的证据表明，异常的免疫反应导致 T2D 患者的高血糖，相反，胰岛素抵抗是自身免疫性糖尿病发病机制的一部分。然而，尚未完全阐明在 T2D 患者中存在常规自身免疫标志物（如自身抗体）的程度会如何影响疾病的自然病程，特别是影响对各种治疗的反应。该领域未来研究的挑战是发现新的遗传、分子或表型指标，这些指标将能够对 T2D 患者的特定亚人群进行特征描述，这些亚人群将从将免疫调节疗法添加到标准降血糖治疗中获益最大。本文综述旨在讨论免疫系统可能参与 T2D 和肥胖代谢紊乱发展的推测机制，并探讨免疫疗法在该疾病及其并发症未来管理中的潜在作用。
