title: Serum high-mobility group box-1 levels are positively associated with micro- and macroalbuminuria but not with cardiovascular disease in type 1 diabetes: the EURODIAB Prospective Complications Study.
abstract: OBJECTIVE
  High-mobility group box-1 (HMGB1) is a pro-inflammatory cytokine that may contribute to the pathogenesis of micro- and macrovascular complications commonly observed in diabetes. We investigated whether HMGB1 is associated with: i) markers of low-grade inflammation (LGI) and endothelial dysfunction (ED) and pulse pressure (PP, a marker of arterial stiffness); ii) prevalent nephropathy, retinopathy and cardiovascular disease (CVD) in type 1 diabetes; and iii) the potential mediating roles of LGI, ED and PP therein.
  
  
  METHODS
  This was a cross-sectional nested case-control study of 463 patients (226 women; mean age 40±10 years) with type 1 diabetes from the EURODIAB Prospective Complications Study. We used linear and binary or multinomial logistic regression analyses adjusted for traditional risk factors.
  
  
  RESULTS
  Serum Ln-HMGB1 levels were positively associated with LGI and ED (standardised β=0.07 (95% confidence interval (CI): 0.02-0.12) and β=0.08 (95% CI: 0.02-0.14) respectively), but not with PP. Higher Ln-HMGB1 (per unit) was associated with greater odds of micro- and macroalbuminuria: odds ratio (OR)=1.24 (95% CI: 0.90-1.71) and OR=1.61 (95% CI: 1.15-2.25) respectively, P for trend=0.004. Further adjustments for LGI or ED did not attenuate these associations. No such associations were found between Ln-HMGB1 and estimated glomerular filtration rate (eGFR), retinopathy or CVD, however.
  
  
  CONCLUSIONS
  In type 1 diabetes, higher serum HMGB1 levels are associated with greater prevalence and severity of albuminuria, though not with eGFR, retinopathy and CVD. Prospective studies are needed to clarify the causal role of HMGB1, if any, in the pathogenesis of vascular complications in type 1 diabetes.
authors: Care and Public Health Research Institute, University of Maastricht, Maastricht, The Netherlands. j.nin@maastrichtuniversity.nl
authors: Johanna W M
authors: JW
authors: Nin
authors: Isabel
authors: I
authors: Ferreira
authors: Casper G
authors: CG
authors: Schalkwijk
authors: Martin H
authors: MH
authors: Prins
authors: Nish
authors: N
authors: Chaturvedi
authors: John H
authors: JH
authors: Fuller
authors: Coen D A
authors: CD
authors: Stehouwer
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000652:urine; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000652:urine; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000097:blood / Q000517:prevention & control / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000652:urine; D005060:Europe; D005260:Female; D005919:Glomerular Filtration Rate; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein