Daniel Gordin1, Carol Forsblom1, Nicolae M Panduru2, Merlin C Thomas3, Mette Bjerre4, Aino Soro-Paavonen1, Nina Tolonen1, Niina Sandholm1, Allan Flyvbjerg4, Valma Harjutsalo5, Per-Henrik Groop6. 1. 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. 2. Second Clinical Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania. 3. Diabetic Complications, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia. 4. 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. 5. 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. 6. 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.
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. 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 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.
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 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.
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