• G Gruden, G Bruno, N Chaturvedi, D Burt, S Pinach, C Schalkwijk, C D Stehouwer, D R Witte, J H Fuller, P Cavallo-Perin, and EURODIAB Prospective Complications Study Group.
• Department of Internal Medicine, University of Turin, Italy. gabriella.gruden@unito.it
• J. Intern. Med. 2009 Dec 1; 266 (6): 527-36.

ObjectivesThe 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.DesignA cross-sectional nested case-control study from the EURODIAB Study of 531 type 1 diabetic patients was performed.SubjectsCases (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.ResultsAnti-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].ConclusionsIn 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.

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