title: Osteopontin is a strong predictor of incipient diabetic nephropathy, cardiovascular disease, and all-cause mortality in patients with type 1 diabetes.
abstract: 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.
  
  
  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 µg/L; P = 0.04), progressed to ESRD (28.3 ± 1.7 vs. 15.4 ± 0.2 µg/L; P < 0.001), suffered an incident CVD event (20.2 ± 1.2 vs. 15.5 ± 0.2 µg/L; P < 0.001), or died (23.3 ± 1.4 vs. 15.8 ± 0.2 µg/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.
authors: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, and the Diabetes and Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Daniel
authors: D
authors: Gordin
authors: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, and the Diabetes and Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Carol
authors: C
authors: Forsblom
authors: Second Clinical Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
authors: Nicolae M
authors: NM
authors: Panduru
authors: Diabetic Complications, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors: Merlin C
authors: MC
authors: Thomas
authors: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and the Medical Research Laboratories, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors: Mette
authors: M
authors: Bjerre
authors: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, and the Diabetes and Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Aino
authors: A
authors: Soro-Paavonen
authors: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, and the Diabetes and Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Nina
authors: N
authors: Tolonen
authors: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, and the Diabetes and Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Niina
authors: N
authors: Sandholm
authors: Department of Endocrinology and Internal Medicine, Aarhus University Hospital and the Medical Research Laboratories, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors: Allan
authors: A
authors: Flyvbjerg
authors: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, and the Diabetes and Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, and the Diabetes and Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland.
authors: Valma
authors: V
authors: Harjutsalo
authors: Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, and the Diabetes and Obesity Research Program, Research Program's Unit, University of Helsinki, Helsinki, Finland Diabetic Complications, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia per-henrik.groop@helsinki.fi.
authors: Per-Henrik
authors: PH
authors: Groop
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality*; D002423:Cause of Death; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D053495:Osteopontin / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D053495:Osteopontin