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Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 Cotreatment versus Insulin-Like Growth Factor-I Alone in Two Brothers with Growth Hormone Insensitivity Syndrome: Effects on Insulin Sensitivity, Body Composition and Linear Growth
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- Ekstrom, Klas (author)
- Karolinska Institutet
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- Carlsson-Skwirut, Christine (author)
- Karolinska Institutet
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- Ritzen, E. Martin (author)
- Karolinska Institutet
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- (creator_code:org_t)
- 2011-09-28
- 2011
- English.
- In: HORMONE RESEARCH IN PAEDIATRICS. - : Karger. - 1663-2818 .- 1663-2826. ; 76:5, s. 355-366
- Journal article (peer-reviewed)
Abstract
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- Background/Aims: Growth hormone insensitivity syndrome (GHIS) is caused by a defective growth hormone receptor (GHR) and is associated with insulin-like growth factor-I (IGF-I) deficiency, severely short stature and, from adolescence, fasting hyperglycemia and obesity. We studied the effects of treatment with IGF-I in either a 1:1 molar complex with IGFBP-3 (IGF-I/BP-3-Tx) or with IGF-I alone (IGF-I-Tx) on metabolism and linear growth. Methods: Two brothers, compound heterozygous for a GHR gene defect, were studied. After 8 months without treatment, we examined the short- and long-term effects of IGF-I/BP-3-Tx and, subsequently, IGF-I-Tx on 12-hour overnight levels of IGF-I, GH, insulin, IGFBP-1, insulin sensitivity by hyperinsulinemic euglycemic clamp, body composition by dual-energy X-ray absorptiometry and linear growth. Results: Mean overnight levels of insulin decreased and IGFBP-1, a measure of hepatic insulin sensitivity, increased on both regimens, but was more pronounced on IGF-I-Tx. Insulin sensitivity by clamp showed no consistent changes. Lean body mass increased and abdominal fat mass decreased in both subjects on IGF-I-Tx. However, the changes were inconsistent during IGF-I/BP-3-Tx. Height velocity was low without treatment, increased slightly on IGF-I/BP-3-Tx and doubled on IGF-I-Tx. Conclusion: Both modalities of IGF-I improved determinants of hepatic insulin sensitivity, body composition and linear growth rate; however, IGF-I alone seemed to be more efficient.
Keyword
- Growth hormone insensitivity syndrome; Insulin-like growth factor-I; Body composition; Growth; Children
- MEDICINE
- MEDICIN
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