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ADAMTS13 activity as a novel risk factor for incident type 2 diabetes mellitus: a population-based cohort study

Paul S de Vries1,2, Thijs T W van Herpt1,3, Symen Ligthart1

  • 1Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.

Diabetologia
|October 28, 2016
PubMed
Abstract

Insights

Elevated ADAMTS13 activity, an enzyme, is linked to a higher risk of developing type 2 diabetes and prediabetes. This association appears independent of its role in breaking down von Willebrand factor (VWF).

Area of Science:

  • Biochemistry
  • Endocrinology
  • Vascular Biology

Background:

  • ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) is a protease that cleaves von Willebrand factor (VWF).
  • VWF is implicated in the increased risk of type 2 diabetes mellitus.
  • The relationship between ADAMTS13 activity, VWF antigen levels, and incident diabetes requires further investigation.

Purpose of the Study:

  • To investigate the association between ADAMTS13 activity and VWF antigen levels with the incidence of diabetes.
  • To determine if ADAMTS13 activity is an independent risk factor for diabetes development.

Main Methods:

  • A prospective population-based cohort study (Rotterdam Study) with 5176 participants.
  • Participants were diabetes-free at baseline and followed for over 20 years.
  • Cox proportional hazards models were used to analyze the associations.

Main Results:

  • ADAMTS13 activity was associated with an increased risk of incident diabetes (HR 1.17) and prediabetes (HR 1.11) after adjusting for known risk factors.
  • The association between ADAMTS13 activity and incident diabetes remained significant after adjusting for VWF antigen and glycemic markers.
  • VWF antigen was associated with incident diabetes, but this effect was attenuated after covariate adjustment.

Conclusions:

  • ADAMTS13 activity is an independent risk factor for incident prediabetes and type 2 diabetes.
  • The mechanism linking ADAMTS13 to diabetes may extend beyond its VWF-cleaving function.
  • ADAMTS13 may play a direct role in the pathogenesis of diabetes.
Keywords:
ADAMTS13DiabetesEpidemiologyIncidencePrediabetesRisk factorVon Willebrand factor

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