Effects of duration and age at onset of type 1 diabetes on preclinical manifestations of nephropathy

Abstract

Several studies have reported that the effect of type 1 diabetes disease duration on nephropathy may be greater during or after puberty than an equivalent number of years before puberty. The International Diabetic Nephropathy Study examined the effects of disease duration and age at onset on glomerular morphometry obtained from kidney biopsy in 243 young type 1 diabetic subjects with albumin excretion rates <100 micro g/min: 184 with prepubertal onset, 35 with pubertal onset, and 24 with postpuberty onset. Outcomes included the volume fraction of the glomerulus occupied by the mesangium [Vv(Mes/glom)], glomerular basement membrane (GBM) width, and the surface density of peripheral glomerular capillary basement membrane per glomerulus Sv(PGBM/glom). Vv(Mes/glom) progressed slowly in the first 14 or 15 years after disease onset but more rapidly thereafter. GBM width increased, while Sv(PGBM/glom) decreased with increasing disease duration. No statistically significant differences in the effect of duration were observed among the three age-at-onset subgroups, even with multivariate adjustment for sex, center, baseline HbA(1c) concentration, diastolic blood pressure, height, and BMI. Our results may explain the conflicting results of previous studies regarding the effects of pre-versus postpuberty disease duration.