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

Josh Reed, Steve Bain Orcid Logo, Venkat Kanamarlapudi Orcid Logo

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Volume: 14, Pages: 3567 - 3602

Swansea University Authors: Steve Bain Orcid Logo, Venkat Kanamarlapudi Orcid Logo

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DOI (Published version): 10.2147/dmso.s319895

Abstract

Type 2 diabetes (T2D), which has currently become a global pandemic, is ametabolic disease largely characterised by impaired insulin secretion and action. Significantprogress has been made in understanding T2D aetiology and pathogenesis, which is discussedin this review. Extrapancreatic pathology is...

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Published in: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
ISSN: 1178-7007
Published: Informa UK Limited 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa57318
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spelling 2022-01-04T17:10:24.0727784 v2 57318 2021-07-14 A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives 5399f4c6e6a70f3608a084ddb938511a 0000-0001-8519-4964 Steve Bain Steve Bain true false 63741801137148abfa4c00cd547dcdfa 0000-0002-8739-1483 Venkat Kanamarlapudi Venkat Kanamarlapudi true false 2021-07-14 MEDS Type 2 diabetes (T2D), which has currently become a global pandemic, is ametabolic disease largely characterised by impaired insulin secretion and action. Significantprogress has been made in understanding T2D aetiology and pathogenesis, which is discussedin this review. Extrapancreatic pathology is also summarised, which demonstrates the highlymultifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsiblefor augmenting insulin secretion from pancreatic beta-cells during the postprandialperiod. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a muchlonger half-life have been developed, which are currently an effective treatment option for T2Dby enhancing insulin secretion in patients. Interestingly, there is continual emerging evidencethat 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 analternative to bariatric surgery, a procedure associated with numerous complications. CurrentGLP-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 havebeen developed for these sites to test their therapeutic potential. Recent studies have alsodemonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptorsincluding 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-1Rmechanisms of activation via different agonists, will likely provide better insight into thetherapeutic potential of GLP-1-based therapies to treat T2D. Journal Article Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 14 3567 3602 Informa UK Limited 1178-7007 diabesity, GLP-1, GLP-1R, incretin effect, insulin, metabolic homeostasis 10 8 2021 2021-08-10 10.2147/dmso.s319895 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University External research funder(s) paid the OA fee (includes OA grants disbursed by the Library) UKRI BBSRC - BB/F017596/1; BB/C515455/2; BB/S019588/1; MRC - G0401232 2022-01-04T17:10:24.0727784 2021-07-14T11:33:24.1061839 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Josh Reed 1 Steve Bain 0000-0001-8519-4964 2 Venkat Kanamarlapudi 0000-0002-8739-1483 3 57318__20600__7cb4cefacb6948308c8b69eef72abda1.pdf T2D pathogenesis and treatment review DMSO_TT21.pdf 2021-08-10T10:37:07.1668727 Output 11238144 application/pdf Version of Record true © 2021 Reed et al. This work is licensed under a Creative Commons Attribution License true eng http://creativecommons.org/licenses/by/4.0/
title A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
spellingShingle A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
Steve Bain
Venkat Kanamarlapudi
title_short A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
title_full A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
title_fullStr A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
title_full_unstemmed A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
title_sort A Review of Current Trends with Type 2 Diabetes Epidemiology, Aetiology, Pathogenesis, Treatments and Future Perspectives
author_id_str_mv 5399f4c6e6a70f3608a084ddb938511a
63741801137148abfa4c00cd547dcdfa
author_id_fullname_str_mv 5399f4c6e6a70f3608a084ddb938511a_***_Steve Bain
63741801137148abfa4c00cd547dcdfa_***_Venkat Kanamarlapudi
author Steve Bain
Venkat Kanamarlapudi
author2 Josh Reed
Steve Bain
Venkat Kanamarlapudi
format Journal article
container_title Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
container_volume 14
container_start_page 3567
publishDate 2021
institution Swansea University
issn 1178-7007
doi_str_mv 10.2147/dmso.s319895
publisher Informa UK Limited
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Type 2 diabetes (T2D), which has currently become a global pandemic, is ametabolic disease largely characterised by impaired insulin secretion and action. Significantprogress has been made in understanding T2D aetiology and pathogenesis, which is discussedin this review. Extrapancreatic pathology is also summarised, which demonstrates the highlymultifactorial nature of T2D. Glucagon-like peptide (GLP)-1 is an incretin hormone responsiblefor augmenting insulin secretion from pancreatic beta-cells during the postprandialperiod. Given that native GLP-1 has a very short half-life, GLP-1 mimetics with a muchlonger half-life have been developed, which are currently an effective treatment option for T2Dby enhancing insulin secretion in patients. Interestingly, there is continual emerging evidencethat 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 analternative to bariatric surgery, a procedure associated with numerous complications. CurrentGLP-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 havebeen developed for these sites to test their therapeutic potential. Recent studies have alsodemonstrated the potential of bi- and tri-agonists, which target multiple hormonal receptorsincluding 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-1Rmechanisms of activation via different agonists, will likely provide better insight into thetherapeutic potential of GLP-1-based therapies to treat T2D.
published_date 2021-08-10T14:11:20Z
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