SERUM HSP27 AND DIABETIC COMPLICATIONS IN THE EURODIAB PROSPECTIVE COMPLICATIONS STUDY: A NOVEL CIRCULATING MARKER FOR DIABETIC NEUROPATHY

Abstract

OBJECTIVE Heat shock protein 27 (HSP27) is a member of the small heat shock protein family of proteins. HSP27 expression is enhanced in target tissues of diabetic microvascular complications and changes in circulating HSP27 levels (sHSP27) have been reported in patients with macrovascular disease. We investigated whether sHSP27 levels were associated with micro- and macrovascular complications in type 1 diabetic patients.

RESEARCH DESIGN AND METHODS A cross-sectional nested case-control study from the EURODIAB Prospective Complications Study of 531 type 1 diabetic patients was performed. 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 sHSP27 levels and investigated their associations with diabetic complications.

RESULTS Mean sHSP27 levels were significantly higher in cases with distal symmetrical polyneuropathy (DSP) than in controls, even after adjustment for age and AER (785.9 vs 574.7 pg/ml, p=0.03). In logistic regression analysis, sHSP27 levels in the upper quartile were associated with a twofold increased odds ratio of DSP, independently of conventional risk factors, markers of inflammation, and AER (OR=2.41, 95% CI 1.11-5.24).

CONCLUSION In this large cohort of type 1 diabetic subjects, we found an independent association between sHSP27 and DSP. This suggests that sHSP27 levels may be a novel marker for diabetic neuropathy.