Changes in nocturnal leptin and insulin concentrations in prepubertal low birth weight children after administration of the IGF-I/IGFBP-3 complex.

BACKGROUND: There is limited information regarding the effects of IGF-I and/or IGFBP-3 on circulating leptin concentrations. AIM: To determine the effects of IGF-I on leptin and insulin concentrations, we examined leptin and insulin nocturnal profiles before and after the administration of the IGF-I/IGFBP-3 complex (Iplex) to prepubertal, low birth weight children. METHODS: We studied 20 prepubertal children (11 boys and 9 girls), born after a full-term pregnancy with a mean birth weight below 2.8 kg. They were studied at the mean age of 7.3 +/- 0.5 years (range 4-11 years). Their mean height was -1.8 +/- 0.3 SDS and their mean BMI was 0.1 +/- 0.2 SDS at the time of the study. The children were studied on 2 separate occasions, the first under basal conditions, and the second time after s.c. administration of 1 mg/kg of Iplex at 21.00 h. Blood samples for determination of leptin and insulin were obtained every 60 min between 23.00 h and 07.00 h, while the children were sleeping. In each patient, we calculated the leptin and insulin mean area under the curve, both under basal conditions and after the administration of the IGF-I/IGFBP-3 complex. RESULTS: Mean nocturnal leptin area under the curve exhibited a significant increase (2.7 +/- 2.1 vs. 11.2 +/- 2.6 ng/ml h, p < 0.05), whereas that for mean insulin showed a slight decrease, which did not reach statistical significance after administration of the IGF-I/IGFBP-3 complex. CONCLUSION: These findings indicate that administration of the IGF-I/IGFBP-3 complex increases circulating leptin concentrations in short prepubertal, small for gestational age children, suggesting that IGF-I and/or IGFBP-3 may stimulate leptin secretion by adipose tissue.

Effects of the IGF-I/IGFBP-3 complex on GH and ghrelin nocturnal concentrations in low birth weight children.

OBJECTIVE: There is limited information regarding the effects of IGF-I and/or IGFBP-3 on circulating ghrelin concentrations. To determine the effects of IGF-I on GH and ghrelin concentrations, we examined the GH and ghrelin nocturnal profiles before and after the administration of the IGF-I/-IGFBP-3 complex (Iplex) to low birth weight children. DESIGN: The children were studied on two separate occasions, the first under basal conditions, and the second time after the sc administration of 1 mg/kg of Iplex at 2100 h. Blood samples for determination of GH and ghrelin were obtained every 20 min between 2300 h and 0700 h, while the children were sleeping. In each patient, we calculated the mean GH and ghrelin area under the curve (GH AUC and GHR AUC), both under basal conditions and after the administration of the IGF-I/IGFBP-3 complex. SETTING: The study was performed at a University Research Centre located at a General Hospital in Santiago, Chile. PATIENTS: Twenty prepubertal children (11 boys and 9 girls), born after a full-term pregnancy with a birth weight below 2.8 kg were studied at a mean +/- SEM age of 7.3 +/- 0.5 years (range 4-11 years). Their mean height was -1.8 +/- 0.3 standard deviation score (SDS) and their mean BMI was 0.1 +/- 0.2 SDS at the time of the study. MAIN OUTCOME AND RESULTS: Mean nocturnal GH AUC exhibited a significant decrease (2903 +/- 185 vs 1860 +/- 122 ng/ml min, P < 0.01), whereas mean GHR AUC showed a significant increase after administration of the IGF-I/IGFBP-3 complex (68 +/- 16 vs 288 +/- 36 ng/ml min, P < 0.01). CONCLUSIONS: These findings indicate that the IGF-I/IGFBP-3 complex appears to have opposite effects on circulating GH and ghrelin concentrations in low birth weight children, suggesting that, in addition to its known negative feed-back effect on GH, IGF-I and/or IGFBP-3 may have a positive feed-back effect on ghrelin.

[IGF-I sensitivity in small for gestational age children]. / Sensibilidad a IGF-I en niños pequeños para la edad gestacional.

BACKGROUND: The lack of catch up growth (CUG) in small for gestational age (SGA) children may be related to a reduced sensitivity to insulin growth factor 1 (IGF-I). AIM: To assess the sensitivity to IGF-I in small for gestational age children, measuring basal and post IGF-I nocturnal profile of growth hormone (GH). PATIENTS AND METHODS: We studied 34 prepubertal SGA children aged 4 to 11 years. Twenty three had CUG and 11 did not have CUG. As an IGF-I sensitivity test, nocturnal GH levels were measured every 20 minutes from 23:00 h to 07:00 h, both under baseline conditions and after the administration of a subcutaneous bolus of 1 mg/kg/body weight of the IGF-I + IGFBP-3 complex (Somatokine). RESULTS: At the time of the study, the Z scores for height among children with and without CUG were -1.55 +/- 0.22 and -3.24 +/- 0.28, respectively (p <0.0001). There were no statistical differences between CUG + vs CUG- patients in mean basal GH (6.6 +/- 0.5 and 5.6 +/- 0.6 ng/ml, respectively). After Somatokine administration, mean GH, and the mean GH area under the curve (AUC) decreased significantly in both groups. However, mean overnight GH AUC decreased in all SGA children with CUG, after Somatokine administration, whereas 3 out of 11 SGA children without CUG had an increase in their mean GH AUC in response to Somatokine. CONCLUSIONS: These findings suggest that pituitary sensitivity to IGF-I may be decreased in some SGA children without CUG.

Sensibilidad a IGF-I en niños pequeños para la edad gestacional / IGF-I sensitivity in small for gestational age children

Background: The lack of catch up growth (CUG) in small for gestational age (SGA) children may be related to a reduced sensitivity to insulin growth factor 1 (IGF-I). Aim: To assess the sensitivity to IGF-I in small for gestational age children, measuring basal and post IGF-I nocturnal profile of growth hormone (GH). Patients and methods: We studied 34 prepubertal SGA children aged 4 to 11 years. Twenty three had CUG and 11 did not have CUG. As an IGF-I sensitivity test, nocturnal GH levels were measured every 20 minutes from 23:00 h to 07:00 h, both under baseline conditions and after the administration of a subcutaneous bolus of 1 mg/kg/body weight of the IGF-I + IGFBP-3 complex (Somatokine®). Results: At the time of the study, the Z scores for height among children with and without CUG were -1.55 ± 0.22 and -3.24 ± 0.28, respectively (p <0.0001). There were no statistical differences between CUG + vs CUG- patients in mean basal GH (6.6 ± 0.5 and 5.6 ± 0.6 ng/ml, respectively). After Somatokine® administration, mean GH, and the mean GH area under the curve (AUC) decreased significantly in both groups. However, mean overnight GH AUC decreased in all SGA children with CUG, after Somatokine® administration, whereas 3 out of 11 SGA children without CUG had an increase in their mean GH AUC in response to Somatokine®. Conclusions: These findings suggest that pituitary sensitivity to IGF-I may be decreased in some SGA children without CUG.

Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome.

OBJECTIVE: To determine whether the administration of D-chiro-inositol, a putative insulin-sensitizing drug, would affect the concentration of circulating insulin, the levels of serum androgens, and the frequency of ovulation in lean women with the polycystic ovary syndrome. METHODS: In 20 lean women (body mass index, 20.0 to 24.4 kg/m 2) who had the polycystic ovary syndrome, treatment was initiated with either 600 mg of D-chiro-inositol or placebo orally once daily for 6 to 8 weeks. We performed oral glucose tolerance tests and measured serum sex steroids before and after therapy. To monitor for ovulation, we determined serum progesterone concentrations weekly. RESULTS: In the 10 women given D-chiro-inositol, the mean (+/- standard error) area under the plasma insulin curve after oral administration of glucose decreased significantly from 8,343 +/- 1,149 mU/mL per min to 5,335 +/- 1,792 mU/mL per min in comparison with no significant change in the placebo group (P = 0.03 for difference between groups). Concomitantly, the serum free testosterone concentration decreased by 73% from 0.83 +/- 0.11 ng/dL to 0.22 +/- 0.03 ng/dL, a significant change in comparison with essentially no change in the placebo group (P = 0.01). Six of the 10 women (60%) in the D-chiro-inositol group ovulated in comparison with 2 of the 10 women (20%) in the placebo group (P = 0.17). Systolic (P = 0.002) and diastolic (P = 0.001) blood pressures, as well as plasma triglyceride concentrations (P = 0.001), decreased significantly in the D-chiro-inositol group in comparison with the placebo group, in which these variables either increased (blood pressure) or decreased minimally (triglycerides). CONCLUSION: We conclude that, in lean women with the polycystic ovary syndrome, D-chiro-inositol reduces circulating insulin, decreases serum androgens, and ameliorates some of the metabolic abnormalities (increased blood pressure and hypertriglyceridemia) of syndrome X.