Risk at nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis at type 1 diabetes

OBJECTIVE - The early detection of a rise in albumin excretion within the n ormal range could permit early intervention to prevent the development of m icroalbuminuria (MA) in genetically susceptible subjects with type 1 diabet es. In the Oxford Regional Prospective Study, we prospectively examined uri ne albumin excretion during the first years after diagnosis of childhood ty pe 1 diabetes. RESEARCH DESIGN AND METHODS - Between 1986 and 1995, 511 subjects aged <16 years were recruited at diagnosis and followed for a median of 6 years (ran ge 1-14). In 78 subjects (designated cases), an annual assessment of the al bumin-to-creatinine ratio (ACR) in three morning first-void urine samples d etected MA (males: ACR <greater than or equal to>3.5 mg/mmol, females: ACR greater than or equal to4.0 mg/mmol in two of three urine samples). In 63 o f these subjects and 396 normoalbuminuric diabetic control subjects, rates of change of the ACR were calculated as the slope of the ACR over diabetes duration. RESULTS - The baseline ACR (median [interquartile (IQ) range]), as measured at 1-2.5 years' duration of diabetes, was higher in microalbuminuric subje cts than in the normoalbuminuric subjects (1.0 mg/mmol [0.6-2.1], n = 52, v s. 0.8 mg/mmol [0.6-1.2], n = 303; P = 0.02). The rate of increase of the A CR in the years before the onset of MA was higher in the microalbuminuric s ubjects than in the normoalbuminuric subjects (70% per year [37-149], n = 6 3, vs. 1% per year [-9 to 13], n = 396; P < 0.001). The mean HbA(1c) level after the onset of puberty was weakly correlated with the rate of change of the ACR (r = 0.11, P = 0.024, n = 418). CONCLUSIONS - Higher levels of ACR within the first 2 years after diagnosis and a significantly higher rate of increase of the ACR within the first 5 years from diagnosis can be detected in subjects who subsequently develop M A. HbA(1c) is a determinant of risk for MA, but pubertal factors have a gre ater effect on rates of progression of urine albumin excretion during adole scence in this cohort.