A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives

被引:192
作者
Reed, Josh [1 ]
Bain, Stephen [1 ]
Kanamarlapudi, Venkateswarlu [1 ]
机构
[1] Swansea Univ, Med Sch, Inst Life Sci 1, Swansea SA2 8PP, W Glam, Wales
来源
DIABETES METABOLIC SYNDROME AND OBESITY | 2021年 / 14卷
基金
英国生物技术与生命科学研究理事会; 英国医学研究理事会;
关键词
diabesity; GLP-1; GLP-1R; incretin effect; insulin; metabolic homeostasis; GLUCAGON-LIKE PEPTIDE-1; BETA-CELL FUNCTION; STIMULATED INSULIN-SECRETION; GLP-1 RECEPTOR AGONISTS; AMYLOID POLYPEPTIDE AMYLIN; BODY-MASS INDEX; UNCOUPLING PROTEIN-2; CARDIOVASCULAR-DISEASE; BARIATRIC SURGERY; BLOOD-GLUCOSE;
D O I
10.2147/DMSO.S319895
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Type 2 diabetes (T2D), which has currently become a global pandemic, is a metabolic disease largely characterised by impaired insulin secretion and action. Significant progress has been made in understanding T2D aetiology and pathogenesis, which is discussed in this review. Extrapancreatic pathology is also summarised, which demonstrates the highly multifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsible for augmenting insulin secretion from pancreatic beta-cells during the postprandial period. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a much longer half-life have been developed, which are currently an effective treatment option for T2D by enhancing insulin secretion in patients. Interestingly, there is continual emerging evidence that these therapies alleviate some of the post-diagnosis complications of T2D. Additionally, these therapies have been shown to induce weight loss in patients, suggesting they could be an alternative to bariatric surgery, a procedure associated with numerous complications. Current GLP-1-based therapies all act as orthosteric agonists for the GLP-1 receptor (GLP-1R). Interestingly, it has emerged that GLP-1R also has allosteric binding sites and agonists have been developed for these sites to test their therapeutic potential. Recent studies have also demonstrated the potential of bi-and tri-agonists, which target multiple hormonal receptors including GLP-1R, to more effectively treat T2D. Improved understanding of T2D aetiology/ pathogenesis, coupled with the further elucidation of both GLP-1 activity/targets and GLP-1R mechanisms of activation via different agonists, will likely provide better insight into the therapeutic potential of GLP-1-based therapies to treat T2D.
引用
收藏
页码:3567 / 3602
页数:36
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