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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
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa60093
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) 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.
Keywords: Glucose intolerance; Type 2 diabetes mellitus; Beta-cell function; Insulin sensitivity
College: Faculty of Medicine, Health and Life Sciences
Funders: This research was funded by an unrestricted grant from Novo Nordisk to support research into the pathophysiology of type 2 diabetes mellitus.
Issue: 2
Start Page: 207
End Page: 215

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