ANTI-HSP60 and ANTI-HSP70 antibody levels and micro/ macrovascular complications in type 1 diabetes: the EURODIAB Study

J Intern Med. 2009 Dec;266(6):527-36. doi: 10.1111/j.1365-2796.2009.02129.x. Epub 2009 May 8.


Objectives: The heat shock proteins 60 and 70 (HSP60, HSP70) play an important role in cytoprotection. Under stress conditions they are released into the circulation and elicit an immune response. Anti-HSP60 and anti-HSP70 antibody levels have been associated with cardiovascular disease. Type 1 diabetes is associated with a greatly increased risk of micro- and macrovascular complications. Therefore, we investigated whether anti-HSP60 and anti-HSP70 antibody levels were associated with micro- and macrovascular complications in type 1 diabetic patients.

Design: A cross-sectional nested case-control study from the EURODIAB Study of 531 type 1 diabetic patients was performed.

Subjects: Cases (n = 363) were defined as those with one or more complications of diabetes; control subjects (n = 168) were all those with no evidence of any complication. We measured anti-HSP60 and anti-HSP70 antibody levels and investigated their cross-sectional associations with diabetic complications.

Results: Anti-HSP70 antibody levels were significantly greater in control than in case subjects, whereas anti-HSP60 antibody levels were similar in the two groups. In logistic regression analysis, anti-HSP70 levels in the upper quartiles were associated with a 47% reduced odds ratio of micro/macrovascular complications, independently of conventional risk factors, markers of inflammation and endothelial dysfunction [odds ratio (OR) = 0.53, 95% confidence intervals (CI): 0.28-1.02].

Conclusions: In this large cohort of type 1 diabetic subjects, we found an independent and inverse association between serum anti-HSP70 antibody levels and diabetic micro/macrovascular complications. This suggests that anti-HSP70 antibody levels may be a novel marker of protection from chronic diabetic complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / blood*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / immunology*
  • Case-Control Studies
  • Chaperonin 60 / immunology*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / immunology*
  • Female
  • HSP70 Heat-Shock Proteins / immunology*
  • Humans
  • Male
  • Middle Aged
  • Reference Values
  • Risk Factors
  • Young Adult


  • Antibodies
  • Chaperonin 60
  • HSP70 Heat-Shock Proteins