Two hundred nine consecutive normotensive insulindependent diabetic (IDDM) patients were followed prospectively from November 1982 to January 1988. Patient urinary albumin excretion rate (UAE) had to be normal (<30 mg/24 h) on at least two occasions before inclusion in the study. Patients were aged 18–50 yr with a duration of diabetes of 10–30 yr. UAE was measured every 4 mo, and supine blood pressure was measured annually. Two hundred five patients completed the study. Five years later, 15 patients had developed persistent microalbuminuria with median UAE >30 mg/24 h for at least 2 yr (group 2), and 190 patients stayed normoalbuminuric (group 1). Although within normal range, initial UAE was significantly elevated in group 2 compared with group 1 (mean 19 mg/24 h [range 15–23 mg/24 h] vs. 11 mg/24 h [10–12], 95% confidence interval [Cl], P < 0.001). Initially, there was no difference in blood pressure between group 2 (mean systolic 122 mmHg [117–127], diastolic 80 mmHg [76–84]) and group 1 (mean 126 mmHg [124–128], 79 mmHg [78–80], 95% Cl), and a significant increase in diastolic blood pressure could first be detected during the 3rd yr of persistent microalbuminuria (mean systolic 132 mmHg [124–140], diastolic 85 mmHg [81–89] vs. 128 mmHg [126–130], 79 mmHg [78–80], P < 0.05). Initial hemoglobin A1c was significantly elevated in group 2 compared with group 1 (9.6% [8.8–10.4] vs. 8.5% [8.3–8.7], P < 0.01). Regarding sex, age, duration of diabetes, insulin dose, height, weight, or inverse serum creatinine, no significant differences were seen between the groups. No increase in UAE or blood pressure was detected in group 1, although 38% had experienced at least one elevated UAE during the 5-yr follow-up. Thus, a significant elevation in UAE precedes the increase of systemic blood pressure during the development of nephropathy in IDDM.

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