Reference
Lu, X., Xie, Q., Pan, X., Zhang, R., Zhang, X., Peng, G., Zhang, Y., Shen, S., & Tong, N. (2024). Type 2 diabetes mellitus in adults: Pathogenesis, prevention and therapy. Signal Transduction and Targeted Therapy, 9(1), 1–25. https://doi.org/10.1038/s41392-024-01951-9
Info
FirstAuthor:: Lu, Xi
Author:: Xie, Qingxing
Author:: Pan, Xiaohui
Author:: Zhang, Ruining
Author:: Zhang, Xinyi
Author:: Peng, Ge
Author:: Zhang, Yuwei
Author:: Shen, Sumin
Author:: Tong, Nanwei
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Title:: Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy
Year:: 2024
Citekey:: LuEtAl_2024_Type2Diabetes
itemType:: journalArticle
Journal:: Signal Transduction and Targeted Therapy
Volume:: 9
Issue:: 1
Pages:: 1-25
DOI:: 10.1038/s41392-024-01951-9
Link
Abstract
Type 2 diabetes (T2D) is a disease characterized by heterogeneously progressive loss of islet β cell insulin secretion usually occurring after the presence of insulin resistance (IR) and it is one component of metabolic syndrome (MS), and we named it metabolic dysfunction syndrome (MDS). The pathogenesis of T2D is not fully understood, with IR and β cell dysfunction playing central roles in its pathophysiology. Dyslipidemia, hyperglycemia, along with other metabolic disorders, results in IR and/or islet β cell dysfunction via some shared pathways, such as inflammation, endoplasmic reticulum stress (ERS), oxidative stress, and ectopic lipid deposition. There is currently no cure for T2D, but it can be prevented or in remission by lifestyle intervention and/or some medication. If prevention fails, holistic and personalized management should be taken as soon as possible through timely detection and diagnosis, considering target organ protection, comorbidities, treatment goals, and other factors in reality. T2D is often accompanied by other components of MDS, such as preobesity/obesity, metabolic dysfunction associated steatotic liver disease, dyslipidemia, which usually occurs before it, and they are considered as the upstream diseases of T2D. It is more appropriate to call “diabetic complications” as “MDS-related target organ damage (TOD)”, since their development involves not only hyperglycemia but also other metabolic disorders of MDS, promoting an up-to-date management philosophy. In this review, we aim to summarize the underlying mechanism, screening, diagnosis, prevention, and treatment of T2D, especially regarding the personalized selection of hypoglycemic agents and holistic management based on the concept of “MDS-related TOD”.
Yellow: Interesting
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IR is defined as the loss of the ability of target tissues to respond to insulin signals, resulting in hyperinsulinemia and associated with many metabolic disorders in MDS, such as obesity, MASLD and hypertension
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Obesity associated with overnutrition induces macrophage infiltration and chronic hypoxia, causing low-grade inflammation in the adipose tissue28 and the release of proinflammatory factors such as interleukin (IL)-1β and tumor necrosis factor α (TNF-α),29,30 thus impairing insulin signaling pathway in a number of ways. Firstly, they downregulate the level of insulin signaling molecules at the transcriptional level. Secondly, they activate multiple signaling pathways associated with inflammation (e.g. NF-κB, JAK/STAT and JNK), leading to impaired activation of the molecules. Thirdly, they also accelerate ceramide synthesis, aggravating ectopic lipid deposition.31,32
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NF-κB signaling pathway: N