Format

Send to

Choose Destination
Diabetes Care. 2018 Jul;41(7):1493-1500. doi: 10.2337/dc17-2392. Epub 2018 Apr 11.

Higher Collagen VI Formation Is Associated With All-Cause Mortality in Patients With Type 2 Diabetes and Microalbuminuria.

Author information

1
Nordic Bioscience, Herlev, Denmark dgr@nordicbio.com.
2
Institute of Molecular Medicine, Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.
3
Steno Diabetes Center Copenhagen, Gentofte, Denmark.
4
Nordic Bioscience, Herlev, Denmark.
5
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
6
Department of Medical Endocrinology, Rigshospitalet, Copenhagen, Denmark.
7
Department of Nephrology, Odense University Hospital, Odense, Denmark.
8
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
9
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

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, HbA1c, 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.

PMID:
29643059
DOI:
10.2337/dc17-2392
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center