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Several lines of evidence suggest that endothelial dysfunction and damage present early steps in the pathophysiology of vascular complications in diabetes mellitus [1±3]. Several studies using cultured endothelial cells clearly show that incubation of these cells with high concentrations of glucose leads to severe changes in the proliferation, the adhesive and synthetic properties [1]. Consequently, regulation of vascular relaxation by endothelium becomes disturbed in diabetes [2,3]. In addition to glucose, high concentrations of proinsulin have been shown to promote the synthesis of the plasminogen activator inhibitor type-1 (PAI-1) [4]. This observation indicates that endothelial function can be directly influenced not only by glucose, but also by proinsulin. Thus, high proinsulin levels may contribute to the development of vascular complications in diabetes, if secreted excessively. In line with this assumption proinsulin is increased in the late pre-insulin-dependent diabetes mellitus [5] and especially in non-insulin-dependent diabetic patients with abnormal prohormone convertase PC2 and PC3 activity [6] or with a point mutation in the Diabetologia (1998)

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