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The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM

Gareth Dunseath Orcid Logo, Steve Luzio Orcid Logo, Rajesh Peter, David Owens Orcid Logo

Acta Diabetologica, Volume: 59, Issue: 2, Pages: 207 - 215

Swansea University Authors: Gareth Dunseath Orcid Logo, Steve Luzio Orcid Logo, Rajesh Peter, David Owens Orcid Logo

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DOI (Published version): 10.1007/s00592-021-01785-9

Abstract

AimsThe two predominant pathophysiological defects resulting in glucose intolerance are beta-cell dysfunction and insulin insensitivity. This study aimed to re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early type 2 diabetes (T2DM) em...

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Published in: Acta Diabetologica
ISSN: 0940-5429 1432-5233
Published: Springer Science and Business Media LLC 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa60093
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This study aimed to re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early type 2 diabetes (T2DM) employing highly specific insulin, C-peptide and intact proinsulin assays.Materials and methodsA total of 104 persons with NGT, 85 with impaired glucose tolerance (IGT) and 554 with newly diagnosed T2DM were investigated. Following an overnight fast, all underwent a 4-h standardised mixed meal tolerance test (MTT), and on a second day, a sub-group underwent a frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT) over a 3-h period. The participants were stratified according to fasting glucose and BMI for analysis.ResultsThe MTT revealed that increasing FPG was accompanied by progressively elevated and delayed postprandial glucose peaks. In parallel, following an initial compensatory increase in fasting and postprandial insulin responses there followed a progressive demise in overall beta-cell secretory capacity. FSIVGTT demonstrated a major reduction in the early insulin response to IV glucose in persons with IGT accompanied by a dramatic fall in insulin sensitivity. Beyond pre-diabetes, ever-increasing fasting and postprandial hyperglycaemia resulted predominantly from a progressively decreasing beta-cell secretory function.ConclusionThis study utilising improved assay technology re-affirms that beta-cell dysfunction is evident throughout the spectrum of glucose intolerance, whereas the predominant fall in insulin sensitivity occurs early in its evolution.</abstract><type>Journal Article</type><journal>Acta Diabetologica</journal><volume>59</volume><journalNumber>2</journalNumber><paginationStart>207</paginationStart><paginationEnd>215</paginationEnd><publisher>Springer Science and Business Media LLC</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0940-5429</issnPrint><issnElectronic>1432-5233</issnElectronic><keywords>Glucose intolerance; Type 2 diabetes mellitus; Beta-cell function; Insulin sensitivity</keywords><publishedDay>1</publishedDay><publishedMonth>2</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-02-01</publishedDate><doi>10.1007/s00592-021-01785-9</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm>Not Required</apcterm><funders>This research was funded by an unrestricted grant from Novo Nordisk to support research into the pathophysiology of type 2 diabetes mellitus.</funders><projectreference/><lastEdited>2022-10-27T11:32:11.5576501</lastEdited><Created>2022-05-27T11:33:57.5693604</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>Gareth</firstname><surname>Dunseath</surname><orcid>0000-0001-6022-862X</orcid><order>1</order></author><author><firstname>Steve</firstname><surname>Luzio</surname><orcid>0000-0002-7206-6530</orcid><order>2</order></author><author><firstname>Rajesh</firstname><surname>Peter</surname><order>3</order></author><author><firstname>David</firstname><surname>Owens</surname><orcid>0000-0003-1002-1238</orcid><order>4</order></author></authors><documents><document><filename>60093__24307__4b9d9048a32a4c998051f7e01ca6a7e1.pdf</filename><originalFilename>60093.pdf</originalFilename><uploaded>2022-06-14T12:21:55.0434883</uploaded><type>Output</type><contentLength>1082432</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>&#xA9; The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>http://creativecommons.org/licenses/by/4.0/</licence></document></documents><OutputDurs/></rfc1807>
spelling 2022-10-27T11:32:11.5576501 v2 60093 2022-05-27 The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM fccbba9edcaee08a839a3c5cff8cbe19 0000-0001-6022-862X Gareth Dunseath Gareth Dunseath true false 01491e1cd582746a654fad9addf0de16 0000-0002-7206-6530 Steve Luzio Steve Luzio true false 7feee6f5cccd81493190ce281acebb9c Rajesh Peter Rajesh Peter true false 2fd4b7c3f82c6d3bd546eff61ff944e9 0000-0003-1002-1238 David Owens David Owens true false 2022-05-27 BMS AimsThe two predominant pathophysiological defects resulting in glucose intolerance are beta-cell dysfunction and insulin insensitivity. This study aimed to re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early type 2 diabetes (T2DM) employing highly specific insulin, C-peptide and intact proinsulin assays.Materials and methodsA total of 104 persons with NGT, 85 with impaired glucose tolerance (IGT) and 554 with newly diagnosed T2DM were investigated. Following an overnight fast, all underwent a 4-h standardised mixed meal tolerance test (MTT), and on a second day, a sub-group underwent a frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT) over a 3-h period. The participants were stratified according to fasting glucose and BMI for analysis.ResultsThe MTT revealed that increasing FPG was accompanied by progressively elevated and delayed postprandial glucose peaks. In parallel, following an initial compensatory increase in fasting and postprandial insulin responses there followed a progressive demise in overall beta-cell secretory capacity. FSIVGTT demonstrated a major reduction in the early insulin response to IV glucose in persons with IGT accompanied by a dramatic fall in insulin sensitivity. Beyond pre-diabetes, ever-increasing fasting and postprandial hyperglycaemia resulted predominantly from a progressively decreasing beta-cell secretory function.ConclusionThis study utilising improved assay technology re-affirms that beta-cell dysfunction is evident throughout the spectrum of glucose intolerance, whereas the predominant fall in insulin sensitivity occurs early in its evolution. Journal Article Acta Diabetologica 59 2 207 215 Springer Science and Business Media LLC 0940-5429 1432-5233 Glucose intolerance; Type 2 diabetes mellitus; Beta-cell function; Insulin sensitivity 1 2 2022 2022-02-01 10.1007/s00592-021-01785-9 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Not Required This research was funded by an unrestricted grant from Novo Nordisk to support research into the pathophysiology of type 2 diabetes mellitus. 2022-10-27T11:32:11.5576501 2022-05-27T11:33:57.5693604 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Gareth Dunseath 0000-0001-6022-862X 1 Steve Luzio 0000-0002-7206-6530 2 Rajesh Peter 3 David Owens 0000-0003-1002-1238 4 60093__24307__4b9d9048a32a4c998051f7e01ca6a7e1.pdf 60093.pdf 2022-06-14T12:21:55.0434883 Output 1082432 application/pdf Version of Record true © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License true eng http://creativecommons.org/licenses/by/4.0/
title The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM
spellingShingle The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM
Gareth Dunseath
Steve Luzio
Rajesh Peter
David Owens
title_short The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM
title_full The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM
title_fullStr The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM
title_full_unstemmed The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM
title_sort The pathophysiology of glucose intolerance in newly diagnosed, untreated T2DM
author_id_str_mv fccbba9edcaee08a839a3c5cff8cbe19
01491e1cd582746a654fad9addf0de16
7feee6f5cccd81493190ce281acebb9c
2fd4b7c3f82c6d3bd546eff61ff944e9
author_id_fullname_str_mv fccbba9edcaee08a839a3c5cff8cbe19_***_Gareth Dunseath
01491e1cd582746a654fad9addf0de16_***_Steve Luzio
7feee6f5cccd81493190ce281acebb9c_***_Rajesh Peter
2fd4b7c3f82c6d3bd546eff61ff944e9_***_David Owens
author Gareth Dunseath
Steve Luzio
Rajesh Peter
David Owens
author2 Gareth Dunseath
Steve Luzio
Rajesh Peter
David Owens
format Journal article
container_title Acta Diabetologica
container_volume 59
container_issue 2
container_start_page 207
publishDate 2022
institution Swansea University
issn 0940-5429
1432-5233
doi_str_mv 10.1007/s00592-021-01785-9
publisher Springer Science and Business Media LLC
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
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
document_store_str 1
active_str 0
description AimsThe two predominant pathophysiological defects resulting in glucose intolerance are beta-cell dysfunction and insulin insensitivity. This study aimed to re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early type 2 diabetes (T2DM) employing highly specific insulin, C-peptide and intact proinsulin assays.Materials and methodsA total of 104 persons with NGT, 85 with impaired glucose tolerance (IGT) and 554 with newly diagnosed T2DM were investigated. Following an overnight fast, all underwent a 4-h standardised mixed meal tolerance test (MTT), and on a second day, a sub-group underwent a frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT) over a 3-h period. The participants were stratified according to fasting glucose and BMI for analysis.ResultsThe MTT revealed that increasing FPG was accompanied by progressively elevated and delayed postprandial glucose peaks. In parallel, following an initial compensatory increase in fasting and postprandial insulin responses there followed a progressive demise in overall beta-cell secretory capacity. FSIVGTT demonstrated a major reduction in the early insulin response to IV glucose in persons with IGT accompanied by a dramatic fall in insulin sensitivity. Beyond pre-diabetes, ever-increasing fasting and postprandial hyperglycaemia resulted predominantly from a progressively decreasing beta-cell secretory function.ConclusionThis study utilising improved assay technology re-affirms that beta-cell dysfunction is evident throughout the spectrum of glucose intolerance, whereas the predominant fall in insulin sensitivity occurs early in its evolution.
published_date 2022-02-01T04:17:55Z
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score 11.016235

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