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ADAMTS13 predicts renal and cardiovascular events in type 2 diabetic patients and response to therapy

Erica Rurali1, Marina Noris, Antonietta Chianca

  • 1IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Bergamo, Italy.

Diabetes
|June 5, 2013
PubMed

Insights

In diabetic patients, the ADAMTS13 618Ala variant is linked to reduced enzyme activity and increased risk of complications. This variant may predict a better response to ACE inhibitors, aiding early therapeutic intervention.

Area of Science:

  • Nephrology
  • Cardiology
  • Genetics
  • Pharmacogenomics

Background:

  • Impaired ADAMTS13 proteolysis of von Willebrand factor (VWF) multimers in diabetes may worsen renal and cardiovascular complications.
  • Physiological VWF handling restoration might contribute to the protective effects of ACE inhibitors (ACEi).

Purpose of the Study:

  • To investigate the interaction between ADAMTS13 Pro618Ala variants, ADAMTS13 activity, and ACEi therapy in predicting renal and cardiovascular complications in type 2 diabetic patients.
  • To determine if ADAMTS13 genetic variants influence the efficacy of ACEi in preventing diabetic complications.

Main Methods:

  • Genotyping of 1,163 normoalbuminuric type 2 diabetic patients from the BENEDICT trial for the ADAMTS13 Pro618Ala polymorphism.
  • Analysis of the interaction between the Pro618Ala variant and ACEi treatment on renal and cardiovascular event risk.
  • Measurement of serum ADAMTS13 activity in a substudy and correlation with clinical outcomes.

Main Results:

  • A significant interaction was observed between the ADAMTS13 Pro618Ala variant and ACEi therapy in predicting renal and combined renal/cardiovascular events.
  • Patients with the 618Ala variant exhibited lower ADAMTS13 activity and a higher risk of complications, especially when not on ACEi therapy.
  • ADAMTS13 activity was significantly lower in patients with events compared to controls and negatively correlated with all outcomes.

Conclusions:

  • The ADAMTS13 618Ala variant is associated with reduced proteolytic activity, increased risk of chronic complications in diabetes, and a potentially better response to ACEi therapy.
  • Screening for the ADAMTS13 Pro618Ala polymorphism could identify high-risk diabetic patients who may benefit most from early reno- and cardioprotective ACEi therapy.

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