Endotrophin as a risk marker of mortality and kidney complications in a type 1 diabetes cohort

Hyperglycemia triggers pathological pathways leading to fibrosis, where extracellular matrix (ECM) components are accumulated. We investigated the potential of endotrophin, a pro-fibrotic molecule generated during collagen type VI formation, as a risk marker for complications to type 1 diabetes. End...

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Published in:Frontiers in molecular biosciences Vol. 10; p. 1229579
Main Authors: Møller, Alexandra Louise, Tougaard, Ninna Hahn, Rasmussen, Daniel Guldager Kring, Genovese, Federica, Rønn, Pernille Falberg, Hansen, Tine Willum, Karsdal, Morten Asser, Rossing, Peter
Format: Journal Article
Language:English
Published: Frontiers Media S.A 01.09.2023
Subjects:
biomarker
collagen
diabetes complications
endotrophin
extracellular matrix
fibrosis
Molecular Biosciences
ISSN:2296-889X, 2296-889X
Online Access:Get full text
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Summary:Hyperglycemia triggers pathological pathways leading to fibrosis, where extracellular matrix (ECM) components are accumulated. We investigated the potential of endotrophin, a pro-fibrotic molecule generated during collagen type VI formation, as a risk marker for complications to type 1 diabetes. Endotrophin was measured in serum and urine from 1,468 persons with type 1 diabetes. Outcomes included a composite kidney endpoint, first major adverse cardiovascular event (MACE), all-cause mortality, progression of albuminuria, incident heart failure, and sight-threatening diabetic eye disease. Cox proportional hazards models adjusted for conventional risk factors were applied. A doubling of serum endotrophin was independently associated with the kidney endpoint ( n = 30/1,462; hazard ratio 3.39 [95% CI: 1.98–5.82]), all-cause mortality ( n = 93/1,468; 1.44 [1.03–2.0]), and progression of albuminuria ( n = 80/1,359; 1.82 [1.32–2.52]), but not with first MACE, heart failure, or sight-threatening diabetic eye disease after adjustment. Urinary endotrophin was not associated with any outcome after adjustment. Serum endotrophin was a risk marker for mortality and kidney complications in type 1 diabetes. Biomarkers of ECM remodeling, such as serum endotrophin, may identify persons with active pro-fibrotic processes at risk for complications in diabetes and where antifibrotic agents may reduce this risk.
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Edited by: Arkadeep Mitra, City College, Kolkata, India
Trisha Bansal, University of Illinois Chicago, United States
Reviewed by: Dinesh Yadav, University of Alabama at Birmingham, United States
ISSN:2296-889X
2296-889X
DOI:10.3389/fmolb.2023.1229579