Revisiting the pattern of loss of β-cell function in preclinical Type 1 Diabetes

Martino, Mariangela, Galderisi, Alfonso, Evans-Molina, Carmella and Dayan, Colin ORCID: https://orcid.org/0000-0002-6557-3462 2024. Revisiting the pattern of loss of β-cell function in preclinical Type 1 Diabetes. Diabetes , db240163. 10.2337/db24-0163

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Abstract

Type 1 diabetes (T1D) results from beta cell destruction due to autoimmunity. It has been proposed that beta cell loss is relatively quiescent in the early years after seroconversion to islet antibody positivity (stage 1) with accelerated beta cell loss only developing around 6-18 months prior to clinical diagnosis. This construct implies that immunointervention in this early stage will be of little benefit since there is little disease activity to modulate. Here we argue that the apparent lack of progression in early stage disease may be an artefact of the modality of assessment used. When substantial β-cell function remains, the standard assessment - the oral glucose tolerance test - represents a submaximal stimulus and underestimates the residual function. By contrast, around the time of diagnosis, glucotoxicity exerts a deleterious effect on insulin secretion giving the impression of disease acceleration. Once glucotoxicity is relieved by insulin therapy, β-cell function partially recovers (“the honeymoon effect”). However, evidence from recent trials suggests that glucose control has little effect on the underlying disease process. We therefore hypothesise that the autoimmune destruction of β-cells actually progresses at a more or less constant rate through all phases of T1D and that early stage immunointervention will be both beneficial and desirable.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Medicine
Publisher:	American Diabetes Association
ISSN:	0012-1797
Date of First Compliant Deposit:	3 October 2024
Date of Acceptance:	25 July 2024
Last Modified:	07 Oct 2024 19:56
URI:	https://orca.cardiff.ac.uk/id/eprint/172555

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