CONTRIBUTION OF GROWTH-HORMONE AND IGF-I TO EARLY DIABETIC NEPHROPATHY IN TYPE-1 DIABETES

In children and adolescents with type 1 diabetes, we have reported an association between duration of puberty and the prevalence of nephrome galy and microalbuminuria (MA), which are early markers of diabetic ne phropathy. Growth hormone (GH), IGF-I, testosterone, and prorenin are potential mediators of this effect. This study examined the relationsh ip of these hormonal factors to kidney volume (KV) and MA in 155 subje cts (78 males, age 13.2 +/- 3.5 years [mean +/- SD]) with similar diab etes duration (6.83 +/- 1.6 years) but varying pubertal experience (0- 10 years). KV (by ultrasound), plasma IGF-I, testosterone, prorenin, a nd NaLi countertransport, and urinary albumin, urinary GH, and urinary IGF-I from three 24-h collections were measured. Multiple regression analysis showed that BSA (P +/- 0.0001) and urinary IGF-I (P = 0.001) were significantly associated with KV. MA subjects (albumin excretion rate 15-200 mu g/min) had higher urinary IGF-I (P = 0.005) and urinary GH (P = 0.05) compared with normoalbuminuric subjects. Only 9% of the variance in urinary IGF-I could be attributed to plasma IGF-I (r = 0. 30, P < 0.0001). Testosterone and prorenin were not associated with MA , but they were associated with KV in univariate analyses. The strong association of urinary IGF-I with KV, a marker for glomerular hypertro phy, and of both urinary IGF-I and urinary GH with RIA suggests a role for these growth factors in the development of human diabetic nephrop athy. Together, these data support animal studies that have shown that renal GH and IGF-I may contribute significantly to the pathogenesis o f early diabetic nephropathy.