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

Abstract

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.

The Rotterdam Study: 2018 update on objectives, design and main results

“…Also we reported that serum apoCIII levels as well as apoCIII-to-apoA1 ratio were associated with incident diabetes independent of known risk factors [ 59 ]. ADAMTS13, a novel homeostatic factor, was an independent risk factor for incident prediabetes and type 2 diabetes [ 60 ]. In women, we found that low levels of sex hormone-binding globuline and high levels of total estradiol were associated with increased risk of T2D, independent of potential intermediate risk factors such as obesity, glucose and insulin levels [ 57 ].…”

Von Willebrand factor and ADAMTS13 activity in relation to risk of dementia: a population-based study

“…Suggested roles include inflammation, angiogenesis, and extracellular matrix integrity 13 , each of which have been implicated also in the aetiology of dementia 14 – 16 . A versatile role of ADAMTS13 was further suggested, when we recently showed that high activity of ADAMTS13 relates to a higher risk of diabetes in the general population 17 . The underlying mechanisms remain elusive, but these studies jointly highlight the need for investigation of ADAMTS13 in the context of, as well as beyond its proteolytic activity of VWF.…”

A Disintegrin and Metalloproteinase with Thrombospondin Motifs 18 Deficiency Leads to Visceral Adiposity and Associated Metabolic Syndrome in Mice

“…25 In addition, a population-based cohort study showed that ADAMTS13 activity may be an independent risk factor for incident prediabetes and type 2 diabetes. 26 Furthermore, ADAMTS5 promoted murine adipogenesis and the development of visceral (gonadal) white adipose tissue (vWAT) and associated angiogenesis. 27 Moreover, loss of ADAMTS5 enhances brown adipose mass and promotes browning of white adipose tissue via cAMP response elementebinding protein signaling in mice.…”