title: Endothelial dysfunction precedes development of microalbuminuria in IDDM.
abstract: 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 micrograms/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 micrograms/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 approximately 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.
authors.affiliation: Department of Internal Medicine, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: C D
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: H R
authors.initials: HR
authors.lastname: Fischer
authors.forename: A W
authors.initials: AW
authors.lastname: van Kuijk
authors.forename: B C
authors.initials: BC
authors.lastname: Polak
authors.forename: A J
authors.initials: AJ
authors.lastname: Donker
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000209:etiology* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000209:etiology / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000209:etiology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D014841:von Willebrand Factor