Increased active von Willebrand factor during disease development in the aging diabetic patient population

Abstract

Type 2 diabetes is known to cause endothelial activation resulting in the secretion of von Willebrand factor (VWF). We have shown that levels of VWF in a glycoprotein Ib-binding conformation are increased in specific clinical settings. The aim of the current study is to investigate whether active VWF levels increase during aging and the development of diabetes within the population of patients suffering from type 2 diabetes. Patients and controls were divided into two groups based on age: older and younger than 60 years of age. VWF antigen, VWF propeptide, VWF activation factor and total active VWF were measured. Patients older than 60 years of age had increased levels of total active VWF, VWF activation factor and VWF propeptide compared to younger patients and controls. All measured VWF parameters were associated with age in diabetic patients. Total active VWF and VWF propeptide correlated with the period of being diagnosed with diabetes. Regression analyses showed that especially the VWF activation factor was strongly associated with diabetes in patients older than 60 years of age. In conclusion, we found that the conformation of VWF could be involved in the disease process of diabetes and that the VWF in a glycoprotein Ib-binding conformation could play a role as risk marker during the development of diabetes in combination with an increase in age. Our study shows that the active quality of VWF was more important than the quantity.

Aging Hemostasis: Changes to Laboratory Markers of Hemostasis As We Age—A Narrative Review

“…These substantially include cancer, 118 sedentary lifestyle, 119 autoimmune disorders, 120 and diabetes. 54,121 Nevertheless, the association of elevated procoagulant status with increased thrombosis risk is also evident, given the recognized association of many of the hemostasis markers described here with thrombosis and the simple fact that thrombosis rates increase with aging. As briefly mentioned in the introduction, the findings reported here have also additional important implications for clinical and laboratory practice.…”

“…53 Increasing levels of VWF with aging may also be confounded by additional age associated pathologies including, for example, diabetes. 54 Changes in VWF with age have a particular implication in altered perceptions of VWD diagnosis, as briefly explored at the end of this article.…”

von Willebrand factor propeptide: biology and clinical utility

“…VWFpp and VWF levels have also been used to identify endothelial cell activation in diabetes. 67,69,[75][76][77] A significant increase in VWF and VWFpp were identified in insulin-dependent diabetic patients with microalbunimuria or overt diabetic nephropathy. 67,75 The study by Verrotti et al demonstrated that endothelial dysfunction is present at least 2 years before the development of persistent microalbuminuria.…”

Role of Von Willebrand Factor in Type 2 Diabetes Mellitus Patients

“…The increasing knowledge regarding how and how soon the endothelium can be injured and the release of a large variety of biologic markers has recently led to the assumption that these markers can be a surrogate for endothelial dysfunction. 21,22 Vascular endothelium damage is characterised by an increase of endothelium-derived regulatory proteins. Plasma markers of endothelial dysfunction like von Willebrand factor (vWF), cellular adhesion molecules (CAD), endothelin 1 (ET1), selectin, thrombomodulin may be useful to investigate early endothelium involvement.…”