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Updates of precision medicine in type 2 diabetes.

ABSTRACT: Diabetes mellitus is prevalent worldwide and affects 1 in 10 adults. Despite the successful development of glucose-lowering drugs, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors recently, the proportion of patients achieving satisfactory glucose control has not risen as expected. The heterogeneity of diabetes determines that a one-size-fits-all strategy is not suitable for people with diabetes. Diabetes is undoubtedly more heterogeneous than the conventional subclassification, such as type 1, type 2, monogenic and gestational diabetes. The recent progress in genetics and epigenetics of diabetes has gradually unveiled the mechanisms underlying the heterogeneity of diabetes, and cluster analysis has shown promising results in the substratification of type 2 diabetes, which accounts for 95% of diabetic patients. More recently, the rapid development of sophisticated glucose monitoring and artificial intelligence technologies further enabled comprehensive consideration of the complex individual genetic and clinical information and might ultimately realize a precision diagnosis and treatment in diabetics.

SUBMITTER: Xia M

PROVIDER: S-EPMC10953763 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Updates of precision medicine in type 2 diabetes.

Xia Mingfeng M Li Xiaoying X

Cambridge prisms. Precision medicine 20230414

Diabetes mellitus is prevalent worldwide and affects 1 in 10 adults. Despite the successful development of glucose-lowering drugs, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors recently, the proportion of patients achieving satisfactory glucose control has not risen as expected. The heterogeneity of diabetes determines that a one-size-fits-all strategy is not suitable for people with diabetes. Diabetes is undoubtedly more heterogeneous th ...[more]

PMID: 38550950

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Project description:Type 1 diabetes (T1D) remains a devastating disease that requires much effort to control. Life-long daily insulin injections or an insulin pump are required to avoid severe complications. With many factors contributing to disease onset, T1D is a complex disease to cure. In this review, the risk factors, pathophysiology and defect pathways are discussed. Results from (pre)clinical studies are highlighted that explore restoration of insulin production and reduction of autoimmunity. It has become clear that treatment responsiveness depends on certain pathophysiological or genetic characteristics that differ between patients. For instance, age at disease manifestation associated with efficacy of immune intervention therapies, such as depleting islet-specific effector T cells or memory B cells and increasing immune regulation. The new challenge is to determine in whom to apply which intervention strategy. Within patients with high rates of insulitis in early T1D onset, therapy depleting T cells or targeting B lymphocytes may have a benefit, whereas slow progressing T1D in adults may be better served with more sophisticated, precise and specific disease modifying therapies. Genetic barcoding and immune profiling may help determining from which new T1D endotypes patients suffer. Furthermore, progressed T1D needs replenishment of insulin production besides autoimmunity reversal, as too many beta cells are already lost or defect. Recurrent islet autoimmunity and allograft rejection or necrosis seem to be the most challenging obstacles. Since beta cells are highly immunogenic under stress, treatment might be more effective with stress reducing agents such as glucagon-like peptide 1 (GLP-1) analogs. Moreover, genetic editing by CRISPR-Cas9 allows to create hypoimmunogenic beta cells with modified human leukocyte antigen (HLA) expression that secrete immune regulating molecules. Given the differences in T1D between patients, stratification of endotypes in clinical trials seems essential for precision medicines and clinical decision making.

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Updates of precision medicine in type 2 diabetes.

Publications

Updates of precision medicine in type 2 diabetes.

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