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


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


METHODS
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
G
Department of Internal Medicine, University of Turin, Italy. gabriella.gruden@unito.it
Bruno
G
G
Chaturvedi
N
N
Burt
D
D
Pinach
S
S
Schalkwijk
C
C
Stehouwer
C D
CD
Witte
D R
DR
Fuller
J H
JH
Cavallo-Perin
P
P
D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000276:immunology*; D016022:Case-Control Studies; D018834:Chaperonin 60 / Q000276:immunology*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000276:immunology*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012307:Risk Factors; D055815:Young Adult
D000906:Antibodies; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins