TY - JOUR

T1 - Endotrophin as a risk marker of mortality and kidney complications in a type 1 diabetes cohort

AU - Møller, Alexandra Louise

AU - Tougaard, Ninna Hahn

AU - Rasmussen, Daniel Guldager Kring

AU - Genovese, Federica

AU - Rønn, Pernille Falberg

AU - Hansen, Tine Willum

AU - Karsdal, Morten Asser

AU - Rossing, Peter

N1 - Publisher Copyright: Copyright © 2023 Møller, Tougaard, Rasmussen, Genovese, Rønn, Hansen, Karsdal and Rossing.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - biomarker

KW - collagen

KW - diabetes complications

KW - endotrophin

KW - extracellular matrix

KW - fibrosis

UR - http://www.scopus.com/inward/record.url?scp=85171292133&partnerID=8YFLogxK

U2 - 10.3389/fmolb.2023.1229579

DO - 10.3389/fmolb.2023.1229579

M3 - Journal article

C2 - 37724129

AN - SCOPUS:85171292133

VL - 10

JO - Frontiers in Molecular Biosciences

JF - Frontiers in Molecular Biosciences

SN - 2296-889X

M1 - 1229579

ER -