Insulin-Like Growth Factor (IGF)-I and -11 and IGFBinding Proteins-l, -2, and -3 in Children and Adolescents with Diabetes Mellitus: Correlation with Metabolic Control and Height Attainment.

The putative effects of diabetes and metabolic control on
circulating levels of insulin-like growth factors (IGFs) and their
binding proteins (IGFBPs) remain controversial. In the present
study, serum levels of IGF-I and IGF-II and IGFBP-1, -2, and -3
were measured in 58 patients (age, 0.8-17 yr) with treated (51
subjects) or untreated (7 subjects) insulin-dependent diabetes
mellitus (IDDM) and were compared with the levels in normal
subjects. In the untreated patients IGF-I and IGF-II were decreased
as compared with the healthy controls. In the treated diabetics
IGF-I and IGF-II were reduced; IGFBP-2 (only in prepubertal
subjects) and IGFBP-3 were increased. Furthermore, age-adjusted
values of IGF-I, IGF-II, and IGFBP-3 were lower in prepubertal than
in pubertal patients. Regression analysis revealed a negative
correlation between hemoglobin (Hb)A1c and standard deviation
scores (SDS) of IGF-I and a positive association between HbA1c and
IGFBP-1 SDS or IGFBP-2 SDS. In the treated patients HbA1c was
positively related to IGFBP-1 SDS and IGFBP-2 SDS when applying
simple regression analysis and to IGFBP-2 SDS when using a multiple
regression model. Strong correlations were observed between height
SDS and IGF-I SDS, IGF-II SDS, and IGFBP-3 SDS in prepubertal
subjects who had had IDDM for at least 2 yr, but not in
adolescents. Such correlations have also been found in healthy
children and adolescents. In conclusion; 1) IDDM is associated with
alterations of the IGF-IGFBP system, which are partially accounted
for by differences in metabolic control and pubertal status; 2) the
lower plasma concentrations of serum IGF-I may play a role in the
pathogenesis of growth impairment of poorly controlled prepubertal,
but not pubertal, children and adolescents with IDDM; and 3) in
addition, a potential role of the altered IGF-IGFBP system for the
development of diabetic late complications is hypothesized.