Endotrophin as a risk marker of mortality and kidney complications in a type 1 diabetes cohort
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Endotrophin as a risk marker of mortality and kidney complications in a type 1 diabetes cohort. / Møller, Alexandra Louise; Tougaard, Ninna Hahn; Rasmussen, Daniel Guldager Kring; Genovese, Federica; Rønn, Pernille Falberg; Hansen, Tine Willum; Karsdal, Morten Asser; Rossing, Peter.
I: Frontiers in Molecular Biosciences, Bind 10, 1229579, 2023.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 370493562