VONWILLEBRAND-FACTOR AND DEVELOPMENT OF DIABETIC NEPHROPATHY IN IDDM

We tested the hypothesis that dysfunction of vascular endothelium, indicated by an increase in plasma level of von Willebrand factor (vWF), is present in patients with insulin-dependent diabetes mellitus (IDDM) who develop diabetic nephropathy (DN). DN was classified as absent (urinary albumin excretion [UAE] rate < 15-mu-g/min), incipient (UAE rate 15-200-mu-g/min) or clinical (UAE rate > 200-mu-g/min). We followed a cohort of 59 patients for a median of 3 yr. At baseline, 52 patients had no DN, 6 had incipient DN, and 1 had clinical DN. At follow-up, 38 patients had no DN (group 1). Incipient DN had developed in 14 patients and worsened in 3 patients. Clinical DN had worsened in 1 patient. Together, these 18 patients comprised group 2. A decrease in UAE was observed in the remaining three patients with incipient DN at baseline (group 3). In group 1, vWF - measured by immunoelectrophoresis and expressed as a percentage of normal - increased slightly (median 10%, range -43 to 145, P = 0.009). In group 2, vWF increased in all patients (median 80%, range -14 to -206, P = 0.0002 vs. baseline and group 1). In group 3, vWF decreased (median -19%, range -44 to -18). After correction for possible confounders, i.e., age, varying duration of follow-up, and initial level of vWF, the difference in vWF change between groups 1 and 2 remained significant (P = 0.009). Poor glycemic control at baseline, estimated by glycosylated hemoglobin, was a significant predictor of increases in vWF in both group 1 and groups 1 and 2 combined. We conclude that dysfunction of vascular endothelium is present in patients who develop DN. Poor glycemic control may be related to endothelial dysfunction in patients with and without DN. Our data suggest that changes in vWF may serve as a useful marker of the state of the vascular endothelium in diabetes.