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http://purl.uniprot.org/citations/26046968http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26046968http://www.w3.org/2000/01/rdf-schema#comment"

Context

Type 1 diabetes (T1D) is characterized by an increased risk of macrovascular complications. Pregnancy-associated plasma protein-A (PAPP-A) generated N- and C-terminal fragments of IGF binding protein-4 (NT-IGFBP-4 and CT-IGFBP-4) have been suggested as cardiac biomarkers.

Objective

The objective of the study was to investigate the prognostic value of IGFBP-4 fragments in a cohort of T1D patients.

Design and patients

We prospectively followed up 178 T1D patients with diabetic nephropathy and 152 T1D patients with normoalbuminuria for 12.6 (range 0.2-12.9) years.

Main outcome measures

Levels of IGF-1, IGF-2, IGFBP-1-4, NT- and CT-IGFBP-4, and PAPP-A at baseline.

Results

During follow-up, 15 patients with normoalbuminuria and 71 patients with nephropathy died. Of these deaths, 8 and 45 were due to fatal cardiovascular events, respectively. Using receiver-operating characteristic curve analyses, patients were divided into subgroups using cutoff values of 261 μg/L NT-IGFBP-4, 81 μg/L CT-IGFBP-4, or 10 mIU/L PAPP-A. All-cause mortality was significantly higher in patients with NT-IGFBP-4 levels (55% vs 16%, P < .001) and CT-IGFBP-4 levels (44% vs 15%, P < .001) above vs below cutoffs. Similarly, cardiovascular mortality was elevated in patients with high NT-IGFBP-4 levels (40% vs 7.8%, P < .001) and high CT-IGFBP-4 levels (30% vs 7.4%, P < .001). After adjustments for nephropathy and traditional cardiovascular risk factors, high NT- and CT-IGFBP-4 levels remained prognostic of cardiovascular mortality with hazard ratios [95% confidence interval (CI)] of 5.81 (95% CI 2.62-12.86) (P < .001) and 2.58 (95% CI 1.10-6.10) (P = .030), respectively. After adjustments, PAPP-A was not associated with overall or cardiovascular death. All IGF protein levels were higher in patients with diabetic nephropathy (P < .001), but no variables associated with mortality.

Conclusion

High IGFBP-4 fragment levels were associated with increased all-cause and cardiovascular mortality rates in T1D patients with and without diabetic nephropathy."xsd:string
http://purl.uniprot.org/citations/26046968http://purl.org/dc/terms/identifier"doi:10.1210/jc.2015-2196"xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/author"Frystyk J."xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/author"Bjerre M."xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/author"Hjortebjerg R."xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/author"Rossing P."xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/author"Tarnow L."xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/author"Parving H.H."xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/author"Jorsal A."xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/pages"3032-3040"xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/title"IGFBP-4 Fragments as Markers of Cardiovascular Mortality in Type 1 Diabetes Patients With and Without Nephropathy."xsd:string
http://purl.uniprot.org/citations/26046968http://purl.uniprot.org/core/volume"100"xsd:string
http://purl.uniprot.org/citations/26046968http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26046968
http://purl.uniprot.org/citations/26046968http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26046968
http://purl.uniprot.org/uniprot/#_P22692-mappedCitation-26046968http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26046968
http://purl.uniprot.org/uniprot/P22692http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/26046968