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Ratter-Rieck, J.M.* ; Zepina, A.* ; Huttasch, M.* ; Kupriyanova, Y.* ; Petrera, A. ; Trenkamp, S.* ; Wagner, R.* ; Schrauwen-Hinderling, V.* ; Herder, C.* ; Roden, M.*

Systemic inflammation and peripheral T cell responses associate with hepatic energy metabolism in recent-onset type 1 diabetes.

Liver Int. 46:e70693 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
People with type 1 diabetes feature lower concentrations of hepatic adenosine-triphosphate (ATP) and inorganic phosphate (Pi), which further decline during the early course of disease. However, it is unknown whether inflammatory pathways are involved in the diabetes-associated alterations of hepatic energy metabolism. Participants (median age 35 years, BMI 21.7 kg/m2, HbA1c 6.0%) of the German Diabetes Study (GDS) with short type 1 diabetes duration (≤ 5 years) underwent 1H/31P magnetic resonance spectroscopy to quantify hepatic lipid content, γATP and Pi concentrations. Inflammatory proteins in serum and in supernatants of stimulated CD4+ and CD8+ T cells were measured by a multiplex assay (OLINK Target 96 Inflammation). Analyses were adjusted for multiple testing with false discovery rate (FDR)-correction. Hepatic γATP concentrations positively correlated with circulating TNFSF14 (r = 0.98, p < 0.001, pFDR = 0.009) and MMP10 (r = 0.71, p = 0.047). Hepatic Pi was positively associated with circulating MMP10 (r = 0.90, p = 0.002), with CD4+ T cell responses, particularly CCL3 (r = 0.74, p = 0.010) and CCL4 (r = 0.75, p = 0.008), and with CD8+ T cell responses, particularly CCL3 (r = 0.86, p = 0.014), CCL4 (r = 0.96, p < 0.001) and TNFSF14 (r = 0.89, p = 0.007). Hepatic lipid content (median 0.4%) negatively correlated with IL-2, IL4, IL-13 and TNF release from CD8+ T cells (all pFDR < 0.05). Even in lean metabolically well-controlled persons with early type 1 diabetes, measures of hepatic energy metabolism strongly associate with a specific inflammatory profile and T cell responses, suggesting a role of pro-inflammatory mechanisms in the regulation of hepatic metabolism, even in the absence of steatotic liver disease. Trial Registration: ClinicalTrial.gov identifier: NCT01055093.
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Publication type Article: Journal article
Document type Scientific Article
Keywords T Cells ; Hepatic Lipid Content ; Inflammation ; Phosphorus Metabolites ; Type 1 Diabetes
ISSN (print) / ISBN 1478-3223
e-ISSN 1478-3231
Journal Liver International
Quellenangaben Volume: 46, Issue: 6, Pages: , Article Number: e70693 Supplement: ,
Publisher Wiley
Publishing Place Oxford
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
Grants Deutsche Diabetes Gesellschaft
Ministerium fur Kultur und Wissenschaft des Landes Nordrhein-Westfalen
Bundesministerium für Forschung, Technologie und Raumfahrt
Bundesministerium für Gesundheit