The Effect of Obesity on Serum Growth Factors, and Insulin-like Growth Factor Binding Protein-3 Proteolysis in Children with Simple Obesity / 대한소아내분비학회지

PURPOSE: In children with simple obesity, spontaneous and stimulated growth hormone (GH) secretion are diminished, but their heights usually are normal or even taller for their age and sex. The exact mechanism to explain the discrepancy between impaired GH secretion and normal height velocity has not been elucidated. In this study, we aimed to determine the level of serum growth factors, and the degree of insulin-like growth factor binding protein (IGFBP)-3 proteolysis, and to assess the alteration of the IGF system associated with accelerated or normal growth in simple obesity. METHODS: We evaluated serum growth factors, and IGFBP-3 proteolysis in 27 obese, 25 obesity risk group, and 28 age-matched control group. We measured serum levels of insulin-like growth factor (IGF)-I, IGFBP-1, -3, and free IGF-I by immuno-radiometric assay and IGFBP-3 fragment by Western immunoblotting. RESULTS: The height was taller in obese children than in lean control group. The results showed no significant difference in the level of serum total IGF-1 and IGFBP-3 between obese and normal control group. Although there was no significant difference in other components, serum free IGF-I levels were significantly increased (P<0.05) and showed positive correlation with their height in obese children (r=0.25, P<0.05). The degree of IGFBP-3 proteolysis was increased in obesity and obesity risk group compared to control group. The densities of the IGFBP-3 proteolytic fragment approximate 18 kDa also showed positive correlation with levels of free IGF-I (r=0.23, P<0.05) and height (r=0.19, P<0.05). CONCLUSION: These findings may suggest that elevated levels of serum IGFBP-3 proteolytic fragments showing decreased affinity to IGF-I result in the increase of biologically active free IGF-I, thereby maintain normal growth in the obese children.

Serum IGF-I, Free IGF-I, IGFBP-1, IGFBP-3 Levels in Children with Intrauterine Growth Retardation / 대한소아내분비학회지

PURPOSE:Most but not all intrauterine growth retardation(IUGR) children has catch-up growth postnatally. However, nothing is known about the predictive parameters on the catch-up growth. The aim of this study was to describe serum IGF-I, free IGF-I, IGFBP-1, and IGFBP-3 levels in IUGR children and to correlate these hormone values with auxologic parameters to investigate their value on the postnatal growth pattern. METHODS:Among children with IUGR born at Ewha Womans University from Jan. 1995 to Aug. 1998, 16 children with IUGR at 3 years of age and 12 age-matched normal controls were studied for auxologic and biologic parameters. We measured height, weight, and serum levels of insulin-like growth factor(IGF)-I, free IGF-I, IGF binding protein(BP)-1, IGFBP-3 using immunoradiometric kits. RESULTS: 1)Among 16 children with IUGR at 3 years of age, 13 children had catch-up growth(81.3%), but 3 children remained short stature(18.7%). The height standard deviation score(SDS) in children with IUGR and control were -0.3+/-0.8 and 0.8+/-0.7, respectively(P0.05). 2)Serum IGF-I levels in children with IUGR at 3 years of age and normal control were 90.9+/-35.4ng/mL and 68.4+/-24.4ng/mL, respectively(p>0.05) and free IGF-I were 0.9+/-0.5ng/mL and 0.6+/-0.3ng/mL(p>0.05), IGFBP-1 were 50.5+/-30.5ng/ mL and 52.3+/-23.2ng/mL(p>0.05), IGFBP-3 were 4,116.7+/-1,062.2ng/mL and 4,058.4+/-808.5ng/mL(p>0.05), respectively. 3)In children with IUGR at 3 years of age, height SDS in IUGR children with catch-up growth and those without catch-up growth were 0.002+/-0.6 and -1.5+/-0.7, respectively(P<0.001), but there were no differences in weight SDS, body mass index, IGF-I, free IGF-I, IGFBP-1 and IGFBP-3. 4)There were no significant correlations between height gain and any growth factors. CONCLUSION: The results show that there is no difference in the levels of IGF-I, free IGF-I, IGFBP-1 and IGFBP-3 in IUGR children at 3 years of age compared to age-matched normal control, suggesting that other factors rather than IGF-I, free IGF-I, IGFBP-1, IGFBP-3 may cause short stature in IUGR.

Growth Status and Levels of Growth Factors in Children with Insulin-dependent Diabetes Mellitus

PURPOSE: It is well known that the linear growth velocity in children with insulin-dependent diabetes mellitus (type 1 DM) is closely related to metabolic control and onset age of the disease. Many studies have demonstrated growth impairment in children with type 1 DM, regardless of the degree of metabolic control, whereas other studies have found no growth retardation. Therefore, we examined the growth status and the level of growth factors in children with type 1 DM, and compared them with healthy children. METHODS: Thirty-six patients with type 1 DM (21 female, 15 male; mean age, 10.8 years : range, 5-15 years)were studied. The mean duration of type 1 DM in these patients was 2.7 years (range, 0.1-7.0 years). Their growth status in height standard deviation score (HTSDS) and levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF-II and IGF-binding protein (IGFBP)-3 were compared with age and sex matched normal children (21 female, 15 male; mean age, 10.3 years; range, 5-15 years). RESULTS: As HTSDS in type 1 DM, children were 0.4 +/- 1.1, no prominent growth impairment was observed in type 1 DM children. IGF-I and IGF-II levels decreased significantly in type 1 DM, but no significant differences in free IGF-I and IGFBP-3 levels compared to normal. Height in type 1 DM children was in direct correlation with free IGF-I (r=0.35, P<0.05) and IGFBP-3 (r= 0.45, P<0.01), respectively. CONCLUSION: This study reveals that the levels of IGF-I and -II are decreased in children with type 1 DM, whereas free IGF-I levels are not. These findings may be related to the decreased IGFBP-3 levels in diabetic children, and may explain no growth impairment, except in cases of extremely poor metabolic control.

Growth Status and Levels of Growth Factors in Children with Insulin-dependent Diabetes Mellitus

PURPOSE: It is well known that the linear growth velocity in children with insulin-dependent diabetes mellitus (type 1 DM) is closely related to metabolic control and onset age of the disease. Many studies have demonstrated growth impairment in children with type 1 DM, regardless of the degree of metabolic control, whereas other studies have found no growth retardation. Therefore, we examined the growth status and the level of growth factors in children with type 1 DM, and compared them with healthy children. METHODS: Thirty-six patients with type 1 DM (21 female, 15 male; mean age, 10.8 years : range, 5-15 years)were studied. The mean duration of type 1 DM in these patients was 2.7 years (range, 0.1-7.0 years). Their growth status in height standard deviation score (HTSDS) and levels of insulin-like growth factor (IGF)-I, free IGF-I, IGF-II and IGF-binding protein (IGFBP)-3 were compared with age and sex matched normal children (21 female, 15 male; mean age, 10.3 years; range, 5-15 years). RESULTS: As HTSDS in type 1 DM, children were 0.4 +/- 1.1, no prominent growth impairment was observed in type 1 DM children. IGF-I and IGF-II levels decreased significantly in type 1 DM, but no significant differences in free IGF-I and IGFBP-3 levels compared to normal. Height in type 1 DM children was in direct correlation with free IGF-I (r=0.35, P<0.05) and IGFBP-3 (r= 0.45, P<0.01), respectively. CONCLUSION: This study reveals that the levels of IGF-I and -II are decreased in children with type 1 DM, whereas free IGF-I levels are not. These findings may be related to the decreased IGFBP-3 levels in diabetic children, and may explain no growth impairment, except in cases of extremely poor metabolic control.

Characteristics of Serum Insulin-like Growth Factor ( IGF ) and IGF-Bindign Protein-3 during Pregnancy / 대한내분비학회지

BACKGROUND: Pregnancy in human and rodents is associated with dramatic matemal metabolic changes. Insulin-like growth factors (IGFs) are mitogenic peptides that are essential for fetal and maternal tissue growth during pregnancy. They circulate complexed primarily with a serum IGF-binding protein (IGFBP-3) which regulates the availability of the IGFs to their specific target tissues. METHODS: To examine the changes of IGFs and IGFB-3 during pregnancy, we measured serum total IGF-I, free IGF-I, IGF-II and IGFBP-3 by using specific radioimmunoassay, immunoradio-metric assay, western ligand blot and western immunoblot. Blood samples were obtained from 88 pregnant women between 6-40 weeks gestation. RESULTS: While serum IGF-I levels increased up to 50% in late pregnancy, serum IGF-II levels remained unchanged. However, serum free IGF-I levels were significantly higher during pregnancy than in nonpregnancy. Western ligand blot analysis revealed that IGFBP-3 in pregnancy serum was significantly decreased at 6 weeks of gestation, continued decreased level until term, and returned to a nonpregnant level by postpartum 10 day. Serum IGFBP-3 profiles in Western immunoblot analysis revealed that 30 kDa fragments of IGFBP-3 were detectable in pregnancy serum but not in nonpregnancy serum. In contrast, serum IGFBP-3 levels using radioimmunoassay was significantly increased in late pregnancy. CONCLUSIONS: 1) serum IGF-I was significantly elevated in late pregnancy 2) serum IGF-II was not significantly changed 3) free IGF-I significantly elevated throughout gestation 4) intact IGFBP-3 was markedly reduced after 6 weeks of gestation.