title: Higher plasma high-mobility group box 1 levels are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12 year follow-up study.
abstract: OBJECTIVE
  This study aimed to investigate the associations of plasma levels of the pro-inflammatory cytokine high-mobility group box 1 (HMGB1) with incident cardiovascular disease (CVD) and all-cause mortality in patients with type 1 diabetes.
  
  
  METHODS
  We prospectively followed 165 individuals with diabetic nephropathy and 168 individuals with persistent normoalbuminuria who were free of CVD at study entry and in whom levels of HMGB1 and other cardiovascular risk factors were measured at baseline.
  
  
  RESULTS
  During the course of follow-up (median, 12.3 years [interquartile range, 7.8-12.5]), 80 patients died, 82 suffered a fatal (n = 46) and/or non-fatal (n = 53) CVD event. After adjustment for age, sex, case-control status and other risk factors, patients with higher levels of log(e) HMGB1 had a higher incidence of fatal and non-fatal CVD and all-cause mortality: HR 1.55 (95% CI 0.94, 2.48) and HR 1.86 (95% CI 1.18, 2.93), respectively. Further adjustments for differences in markers of low-grade inflammation, endothelial and renal dysfunction and arterial stiffness did not attenuate these associations because plasma levels of HMGB1 were not independently associated with these variables.
  
  
  CONCLUSIONS
  In patients with type 1 diabetes, higher levels of plasma HMGB1 are independently associated with a higher risk of all-cause mortality and, to a lesser extent, with a higher incidence of CVD. Larger studies are needed to ascertain more definitely the role of HMGB1 in the development of vascular complications in diabetes.
authors: Department of Internal Medicine, Universiteitssingel 50, 6200 MD, PO Box 616, Maastricht, the Netherlands. j.nin@maastrichtuniversity.nl
authors: J W M
authors: JW
authors: Nin
authors: I
authors: I
authors: Ferreira
authors: C G
authors: CG
authors: Schalkwijk
authors: A
authors: A
authors: Jorsal
authors: M H
authors: MH
authors: Prins
authors: H-H
authors: HH
authors: Parving
authors: L
authors: L
authors: Tarnow
authors: P
authors: P
authors: Rossing
authors: C D A
authors: CD
authors: Stehouwer
mesh_terms: D000419:Albuminuria / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D003718:Denmark / Q000453:epidemiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein