AUTHOR=Møller Alexandra Louise , Tougaard Ninna Hahn , Rasmussen Daniel Guldager Kring , Genovese Federica , Rønn Pernille Falberg , Hansen Tine Willum , Karsdal Morten Asser , Rossing Peter 

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

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2023.1229579

DOI=10.3389/fmolb.2023.1229579

ISSN=2296-889X

ABSTRACT=<p>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 (<italic>n</italic> = 30/1,462; hazard ratio 3.39 [95% CI: 1.98–5.82]), all-cause mortality (<italic>n</italic> = 93/1,468; 1.44 [1.03–2.0]), and progression of albuminuria (<italic>n</italic> = 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.</p>