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

VL - 41

SP - 1493

EP - 1500

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 7

ER -