Endothelial dysfunction precedes development of microalbuminuria in IDDM

Abstract

In patients with insulin-dependent diabetes niellitus (IDDM), microalbuminuria is a predictor of widespread severe microangiopathy and maeroangiopathy.Patients with microalbuniimiria show generalized dysfunction of tiie vascular endothelium, but it Is unknown whether endothelial dysfunction precedes the development of mi croalbuminuria.We examined a cohort of 17 IDDM pa tients at baseline and on three occasions during a follow-up of (median) 64 months (range 51-89).All had normal (<15 fxg/min) urinary albumin excretion (UAE) at the iirst three examinations, At the fourth examina tion, 11 patients had normal UAE and 6 had microal buminuria (median 25,7 jxg/min [range 15,3-42.8]),Compared with patients with normal UAE, microalbuminuric patients had significantly higher plasma levels of von Willebrand factor (vWF), a marker of endothelial dys function, at the second (200% [168-274] vs. 131% [69-186]), third (208% [188-270] vs, 125% [82-190]), and fourth examinations (231% [202-269] vs, 132% [88-208], JP < 0.0001), but not at baseline (128% [98-161] vs* 122% [87-210]).An increase in vWF preceded the occurrence of microalbuminuria by -3 years.The groups did not differ with regard to age, diabetes duration, blood pressure, mean glycated hemoglobin and cholesterol, smoking hab its, or extent of retinopathy* Endothelial dysfunction, as estimated by plasma vWF concentration, precedes and may predict the development of microalbuminuria in IDDM.