Recovery of intracellular glucose uptake in T cells during partial remission of type 1 diabetes

Aims/hypothesis Notwithstanding the irreversible beta cell failure seen in type 1 diabetes, some individuals may experience a special phase named ‘partial remission’ or ‘the honeymoon period’, in which there is a transient recovery of beta cell function. Importantly, this stage of partial remission shows spontaneous immune downregulation, although the exact mechanisms are unclear. Intracellular energy metabolism is crucial for the differentiation and function of T cells, and provides promising targets for immunometabolic intervention strategies, but its role during partial remission is unknown. In this study, we aim to investigate the association between T cell intracellular glucose and fatty acid metabolism and the partial remission phase. Methods This is a cross-sectional study with a follow-up component. Intracellular uptake of glucose and fatty acids by T cells was detected in participants with either new-onset type 1 diabetes or type 1 diabetes that was already in partial remission, and compared with heathy individuals and participants with type 2 diabetes. Subsequently, the participants with new-onset type 1 diabetes were followed up to determine whether they experienced a partial remission (remitters) or not (non-remitters). The trajectory of changes in T cell glucose metabolism was observed in remitters and non-remitters. Expression of programmed cell death-1 (PD-1) was also analysed to investigate possible mechanisms driving altered glucose metabolism. Partial remission was defined when patients had convalescent fasting or 2 h postprandial C-peptide >300 pmol/l after insulin treatment. Results Compared with participants with new-onset type 1 diabetes, intracellular glucose uptake by T cells decreased significantly in individuals with partial remission. The trajectory of these changes during follow-up showed that intracelluar glucose uptake in T cells fluctuated during different disease stages, with a decreased uptake during partial remission that rebounded after remission. This dynamic in T cell glucose uptake was only detected in remitters and not in non-remitters. Further analysis demonstrated that changes of intracellular glucose uptake were found in subsets of $ CD4^{+} $ and $ CD8^{+} $ T cells, including Th17, Th1, $ CD8^{+} $ naive T cells (Tn) and $ CD8^{+} $ terminally differentiated effector memory T cells (Temra). Moreover, glucose uptake in $ CD8^{+} $ T cells was negatively related to PD-1 expression. The intracellular metabolism of fatty acids was not found to be different between new-onset participants and those in partial remission. Conclusions/interpretation Intracellular glucose uptake in T cells was specifically decreased during partial remission in type 1 diabetes and may be related to PD-1 upregulation, which may be involved in the down-modulation of immune responses during partial remission. This study suggests that altered immune metabolism could be a target for interventions at the point of diagnosis of type 1 diabetes. Graphical Abstract.

Medienart:	Artikel

Erscheinungsjahr:	2023
Erschienen:	2023

Enthalten in:	Zur Gesamtaufnahme - volume:66
Enthalten in:	Diabetologia - 66(2023), 8 vom: 10. Juni, Seite 1532-1543

Sprache:	Englisch

Beteiligte Personen:	Tang, Rong [VerfasserIn] Zhong, Ting [VerfasserIn] Lei, Kang [VerfasserIn] Lin, Xiaoxi [VerfasserIn] Li, Xia [VerfasserIn]

Links:	Volltext [lizenzpflichtig]

Themen:	Glucose uptake Intracellular metabolism Partial remission T cell Type 1 diabetes

RVK:	RVK Klassifikation XA 40615

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© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:	10.1007/s00125-023-05938-z

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PPN (Katalog-ID):	OLC2144270198