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.
Gruden, G., Bruno, G., Chaturvedi, N., Burt, D., Pinach, S., Schalkwijk, C., Stehouwer, C. D., Witte, D. R., Fuller, J. H., & Cavallo Perin, P. (2009). ANTI-HSP60 and ANTI-HSP70 antibody levels and micro/ macrovascular complications in type 1 diabetes: the EURODIAB Study. Journal of Internal Medicine, 266(6), 527-536. https://doi.org/10.1111/j.1365-2796.2009.02129.x