Osteopontin Is a Strong Predictor of Incipient Diabetic Nephropathy, Cardiovascular Disease, and All-Cause Mortality in Patients With Type 1 Diabetes

OBJECTIVE Osteopontin (OPN) is a multifunctional protein suggested to be a player in the arterial disease of patients with type 2 diabetes. However, its role for complications in patients with type 1 diabetes (T1D) is unknown. We therefore investigated the associations between OPN and diabetic vascular complications and all-cause mortality in patients with T1D. RESEARCH DESIGN AND METHODS Serum OPN was measured in 2,145 adults with T1D without end-stage renal disease (ESRD; dialysis or transplantation) as part of the Finnish Diabetic Nephropathy (FinnDiane) Study. Data on renal status, cardiovascular disease (CVD), and all-cause mortality during follow-up were verified from medical files, hospital discharge registries, and the Finnish National Death Registry, respectively. The median follow-up time was 10.5 (interquartile range 8.9-11.8) years. RESULTS Serum OPN was higher at baseline in patients who developed incident microalbuminuria (16.0 +/- 0.9 vs. 14.1 +/- 0.2 mg/L; P = 0.04), progressed to ESRD (28.3 +/- 1.7 vs. 15.4 +/- 0.2 mg/L; P < 0.001), suffered an incident CVD event (20.2 +/- 1.2 vs. 15.5 +/- 0.2 mg/L; P < 0.001), or died (23.3 +/- 1.4 vs. 15.8 +/- 0.2 mg/L; P < 0.001) during follow-up. In multivariate Cox regression analysis, OPN was independently associated with the development of incident microalbuminuria, an incident CVD event, and death, after adjustments for associated risk factors. Even after calculating reclassification indexes, OPN was predictive of CVD and all-cause mortality beyond the Framingham risk score covariates and hs-CRP. CONCLUSIONS Serum OPN is a strong predictor of incipient diabetic nephropathy, a first-ever CVD event, and all-cause mortality in patients with T1D. Serum OPN may be of clinical significance for the risk prediction of CVD events in patients with T1D.