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 nephromegaly and microalbuminuria (MA), which are early markers of diabetic nephropathy. Growth hormone (GH), IGF-I, testosterone, and prorenin are potential mediators of this effect. This study examined the relationship of these hormonal factors to kidney volume (KV) and MA in 155 subjects (78 males, age 13.2 +/- 3.5 years [mean +/- SD]) with similar diabetes duration (6.83 +/- 1.6 years) but varying pubertal experience (0-10 years). KV (by ultrasound), plasma IGF-I, testosterone, prorenin, and 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 microg/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 hypertrophy, and of both urinary IGF-I and urinary GH with MA suggests a role for these growth factors in the development of human diabetic nephropathy. Together, these data support animal studies that have shown that renal GH and IGF-I may contribute significantly to the pathogenesis of early diabetic nephropathy.
Department of Pediatrics, the Hospital for Sick Children, University of Toronto, Ontario, Canada. ebs@sickkids.on.ca
E A
EA
Cummings
E B
EB
Sochett
M G
MG
Dekker
M L
ML
Lawson
D
D
Daneman
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000652:urine; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000503:physiopathology* / Q000652:urine; D005260:Female; D019382:Human Growth Hormone / Q000502:physiology* / Q000652:urine; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology* / Q000652:urine; D008297:Male; D011627:Puberty / Q000502:physiology; D013997:Time Factors
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I