Endothelial Dysfunction Precedes Development of Microalbuminuria in IDDM

In patients with insulin-dependent diabetes mellitus (IDDM), microalbuminuria is a predictor of widespread severe microangiopathy and macroangiopathy. Patients with microalbuminuria show generalized dysfunction of the vascular endothelium, but it is unknown whether endothelial dysfunction precedes the development of microalbuminuria. We examined a cohort of 17 IDDM patients at baseline and on three occasions during a follow-up of (median) 64 months (range 51–89). All had normal (< 15 μg/min) urinary albumin excretion (UAE) at the first three examinations. At the fourth examination, 11 patients had normal UAE and 6 had microalbuminuria (median 25.7 μg/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 dysfunction, 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], P < 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 habits, or extent of retinopathy. Endothelial dysfunction, as estimated by plasma vWF concentration, precedes and may predict the development of microalbuminuria in IDDM.