Recently, a dramatic decline in the cumulative incidence of diabetic nephropathy (< 10% after 25 years of diabetes) has been reported in insulin-dependent diabetes mellitus (IDDM) patients diagnosed before the age of 15 years between 1961 and 1980. In a clinic-based study, we assessed recent trends in the incidence of diabetic nephropathy. All 356 patients in whom IDDM was diagnosed before the age of 41 years between 1965 and 1979, identified in 1984, were followed until 1991 or until death. All patients were Caucasians and resided in Copenhagen. The cumulative incidences (life-table method) of diabetic nephropathy (urinary albumin excretion > or = 300 mg/24 h in two out of three consecutive samples) after 15 years of diabetes and in 1991 were 18 +/- 4 and 35 +/- 5% (cumulative incidence +/- SE; onset of diabetes 1965-1969, n = 113), 20 +/- 4 and 35 +/- 5% (onset of diabetes 1970-1974, n = 130), and 16 +/- 5% (onset of diabetes 1975-1979, n = 113), respectively (NS at 15 years). The prevalence of persistent microalbuminuria (31-299 mg/24 h) at time of follow-up was 24% (95% confidence interval: 16-33) in the group with onset of diabetes in 1965-1969, 28% (20-36) with onset of diabetes in 1970-1974, and 19% (13-28) with onset of diabetes in 1975-1979 (NS). The mean +/- SE HbA1c measured yearly beginning in 1984 was higher in patients with nephropathy (9.4 +/- 0.1%) and persistent microalbuminuria (8.9 +/- 0.1%) than in patients with normoalbuminuria (8.5 +/- 0.1%; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)