Aims/hypothesis ADAMTS13 is a protease that breaks down
von Willebrand factor (VWF) multimers into smaller, less
active particles. VWF has been associated with an increased
risk of incident type 2 diabetes mellitus. Here, we determine
whether ADAMTS13 activity and VWF antigen are associated
with incident diabetes.
Methods This study included 5176 participants from the
Rotterdam Study, a prospective population-based cohort
study. Participants were free of diabetes at baseline and
followed up for more than 20 years. Cox proportional hazards
models were used to examine the association of ADAMTS13
activity and VWF antigen with incident diabetes.
Results ADAMTS13 activity was associated with an increased
risk of incident diabetes (HR 1.17 [95% CI 1.08,
1.27]) after adjustment for known risk factors and VWF antigen
levels. Although ADAMTS13 activity was positively associated
with fasting glucose and insulin, the association with
incident diabetes did not change when we adjusted for these
covariates. ADAMTS13 activity was also associated with incident
prediabetes (defined on the basis of both fasting and
non-fasting blood glucose) after adjustment for known risk
factors (HR 1.11 [95% CI 1.03, 1.19]), while the VWF antigen
level was not. VWF antigen was associated with incident diabetes,
but this association was attenuated after adjustment for
known risk factors.
Conclusions/interpretation ADAMTS13 activity appears to
be an independent risk factor for incident prediabetes and type
2 diabetes. As the association between ADAMTS13 and diabetes
did not appear to be explained by its cleavage of VWF,
ADAMTS13 may have an independent role in the development
of diabetes.