Higher collagen VI formation is associated with all-cause mortality in patients with type 2 diabetes and microalbuminuria

Daniel G.K. Rasmussen; Tine W. Hansen; Bernt J. Von Scholten; Signe H. Nielsen; Henrik Reinhard; Hans Henrik Parving; Martin Tepel; Morten A. Karsdal; Peter K. Jacobsen; Federica Genovese; Peter Rossing

doi:10.2337/dc17-2392

Higher collagen VI formation is associated with all-cause mortality in patients with type 2 diabetes and microalbuminuria

Daniel G.K. Rasmussen^*, Tine W. Hansen, Bernt J. Von Scholten, Signe H. Nielsen, Henrik Reinhard, Hans Henrik Parving, Martin Tepel, Morten A. Karsdal, Peter K. Jacobsen, Federica Genovese, Peter Rossing

^*Corresponding author for this work

Department of Clinical Medicine

16 Citations (Scopus)

Abstract

OBJECTIVE Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI formation, is prognostic for adverse outcomes in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS In a prospective, observational study, we measured PRO-C6 in the serum (S-PRO-C6) and urine (U-PRO-C6) of 198 patients with type 2 diabetes and microalbuminuria without symptoms of coronary artery disease. Patients were followed for a median of 6.5 years, and end points were a composite of cardiovascular events (n = 38), all-cause mortality (n = 26), and reduction of estimated glomerular filtration rate (eGFR) of >30% (disease progression [n = 42]). Cox models were unadjusted and adjusted for the conventional risk factors of sex, age, BMI, systolic blood pressure, LDL cholesterol, smoking, HbA _1c , plasma creatinine, and urinary albumin excretion rate. RESULTS Doubling of S-PRO-C6 increased hazards for cardiovascular events (hazard ratio 3.06 [95% CI 1.31–7.14]), all-cause mortality (6.91 [2.96–16.11]), and disease progression (4.81 [1.92–12.01]). Addition of S-PRO-C6 to a model containing conventional risk factors improved relative integrated discrimination by 22.5% for cardiovascular events (P = 0.02), 76.8% for all-cause mortality (P = 0.002), and 53.3% for disease progression (P = 0.004). U-PRO-C6 was not significantly associated with any of the outcomes. CONCLUSIONS S-PRO-C6 generated during COL VI formation predicts cardiovascular events, all-cause mortality, and disease progression in patients with type 2 diabetes and microalbuminuria.

Original language	English
Journal	Diabetes Care
Volume	41
Issue number	7
Pages (from-to)	1493-1500
Number of pages	8
ISSN	0149-5992
DOIs	https://doi.org/10.2337/dc17-2392
Publication status	Published - 2018

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Rasmussen, D. G. K., Hansen, T. W., Von Scholten, B. J., Nielsen, S. H., Reinhard, H., Parving, H. H., Tepel, M., Karsdal, M. A., Jacobsen, P. K., Genovese, F., & Rossing, P. (2018). Higher collagen VI formation is associated with all-cause mortality in patients with type 2 diabetes and microalbuminuria. Diabetes Care, 41(7), 1493-1500. https://doi.org/10.2337/dc17-2392

@article{801694496b5d4ed4abd2fe4982b9d3b9,

title = "Higher collagen VI formation is associated with all-cause mortality in patients with type 2 diabetes and microalbuminuria",

abstract = " OBJECTIVE Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI formation, is prognostic for adverse outcomes in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS In a prospective, observational study, we measured PRO-C6 in the serum (S-PRO-C6) and urine (U-PRO-C6) of 198 patients with type 2 diabetes and microalbuminuria without symptoms of coronary artery disease. Patients were followed for a median of 6.5 years, and end points were a composite of cardiovascular events (n = 38), all-cause mortality (n = 26), and reduction of estimated glomerular filtration rate (eGFR) of >30% (disease progression [n = 42]). Cox models were unadjusted and adjusted for the conventional risk factors of sex, age, BMI, systolic blood pressure, LDL cholesterol, smoking, HbA 1c , plasma creatinine, and urinary albumin excretion rate. RESULTS Doubling of S-PRO-C6 increased hazards for cardiovascular events (hazard ratio 3.06 [95% CI 1.31–7.14]), all-cause mortality (6.91 [2.96–16.11]), and disease progression (4.81 [1.92–12.01]). Addition of S-PRO-C6 to a model containing conventional risk factors improved relative integrated discrimination by 22.5% for cardiovascular events (P = 0.02), 76.8% for all-cause mortality (P = 0.002), and 53.3% for disease progression (P = 0.004). U-PRO-C6 was not significantly associated with any of the outcomes. CONCLUSIONS S-PRO-C6 generated during COL VI formation predicts cardiovascular events, all-cause mortality, and disease progression in patients with type 2 diabetes and microalbuminuria. ",

author = "Rasmussen, {Daniel G.K.} and Hansen, {Tine W.} and {Von Scholten}, {Bernt J.} and Nielsen, {Signe H.} and Henrik Reinhard and Parving, {Hans Henrik} and Martin Tepel and Karsdal, {Morten A.} and Jacobsen, {Peter K.} and Federica Genovese and Peter Rossing",

year = "2018",

doi = "10.2337/dc17-2392",

language = "English",

volume = "41",

pages = "1493--1500",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association",

number = "7",

}

TY - JOUR

T1 - Higher collagen VI formation is associated with all-cause mortality in patients with type 2 diabetes and microalbuminuria

AU - Rasmussen, Daniel G.K.

AU - Hansen, Tine W.

AU - Von Scholten, Bernt J.

AU - Nielsen, Signe H.

AU - Reinhard, Henrik

AU - Parving, Hans Henrik

AU - Tepel, Martin

AU - Karsdal, Morten A.

AU - Jacobsen, Peter K.

AU - Genovese, Federica

AU - Rossing, Peter

PY - 2018

Y1 - 2018

N2 - OBJECTIVE Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI formation, is prognostic for adverse outcomes in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS In a prospective, observational study, we measured PRO-C6 in the serum (S-PRO-C6) and urine (U-PRO-C6) of 198 patients with type 2 diabetes and microalbuminuria without symptoms of coronary artery disease. Patients were followed for a median of 6.5 years, and end points were a composite of cardiovascular events (n = 38), all-cause mortality (n = 26), and reduction of estimated glomerular filtration rate (eGFR) of >30% (disease progression [n = 42]). Cox models were unadjusted and adjusted for the conventional risk factors of sex, age, BMI, systolic blood pressure, LDL cholesterol, smoking, HbA 1c , plasma creatinine, and urinary albumin excretion rate. RESULTS Doubling of S-PRO-C6 increased hazards for cardiovascular events (hazard ratio 3.06 [95% CI 1.31–7.14]), all-cause mortality (6.91 [2.96–16.11]), and disease progression (4.81 [1.92–12.01]). Addition of S-PRO-C6 to a model containing conventional risk factors improved relative integrated discrimination by 22.5% for cardiovascular events (P = 0.02), 76.8% for all-cause mortality (P = 0.002), and 53.3% for disease progression (P = 0.004). U-PRO-C6 was not significantly associated with any of the outcomes. CONCLUSIONS S-PRO-C6 generated during COL VI formation predicts cardiovascular events, all-cause mortality, and disease progression in patients with type 2 diabetes and microalbuminuria.

AB - OBJECTIVE Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI formation, is prognostic for adverse outcomes in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS In a prospective, observational study, we measured PRO-C6 in the serum (S-PRO-C6) and urine (U-PRO-C6) of 198 patients with type 2 diabetes and microalbuminuria without symptoms of coronary artery disease. Patients were followed for a median of 6.5 years, and end points were a composite of cardiovascular events (n = 38), all-cause mortality (n = 26), and reduction of estimated glomerular filtration rate (eGFR) of >30% (disease progression [n = 42]). Cox models were unadjusted and adjusted for the conventional risk factors of sex, age, BMI, systolic blood pressure, LDL cholesterol, smoking, HbA 1c , plasma creatinine, and urinary albumin excretion rate. RESULTS Doubling of S-PRO-C6 increased hazards for cardiovascular events (hazard ratio 3.06 [95% CI 1.31–7.14]), all-cause mortality (6.91 [2.96–16.11]), and disease progression (4.81 [1.92–12.01]). Addition of S-PRO-C6 to a model containing conventional risk factors improved relative integrated discrimination by 22.5% for cardiovascular events (P = 0.02), 76.8% for all-cause mortality (P = 0.002), and 53.3% for disease progression (P = 0.004). U-PRO-C6 was not significantly associated with any of the outcomes. CONCLUSIONS S-PRO-C6 generated during COL VI formation predicts cardiovascular events, all-cause mortality, and disease progression in patients with type 2 diabetes and microalbuminuria.

U2 - 10.2337/dc17-2392

DO - 10.2337/dc17-2392

M3 - Journal article

C2 - 29643059

AN - SCOPUS:85052964464

SN - 0149-5992

VL - 41

SP - 1493

EP - 1500

JO - Diabetes Care

JF - Diabetes Care

IS - 7

ER -

Higher collagen VI formation is associated with all-cause mortality in patients with type 2 diabetes and microalbuminuria

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