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- Decker, Ralph, 1968, et al.
(författare)
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Decreased GH dose after the catch-up growth period maintains metabolic outcome in short prepubertal children with and without classic GH deficiency
- 2012
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Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 77:3, s. 407-15
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Few studies have evaluated metabolic outcomes following growth hormone (GH) treatment in short prepubertal children during different periods of growth. Previously, we found that individualized GH dosing in the catch-up period reduced the variation in fasting insulin levels by 34% compared with those receiving a standard GH dose. We hypothesized that the GH dose required to maintain beneficial metabolic effects is lower during the prepubertal growth phase after an earlier catch-up growth period. DESIGN: Short prepubertal children with isolated GH deficiency or idiopathic short stature were randomized to individualized GH treatment (range, 17-100 mug/kg/day) or a standard dose in a preceding 2-year study. After achieving near mid-parental height(SDS) (,) children receiving an individualized dose were randomized to either a 50% reduced individualized dose (RID, n=28) or an unchanged individualized dose (UID, n=37) for 2 years. The dose remained unchanged in 33 children initially randomized to receive a standard dose (FIX, 43 mug/kg/day).We evaluated whether the variations in metabolic parameters measured during maintenance growth diminished in RID compared with UID or FIX. RESULTS: We observed less variation in fasting insulin levels (-50%), insulin sensitivity as assessed by homeostasis model assessment (-55.1%), lean soft tissue (-27.8%) and bone mineral content (-31.3%) in RID compared with UID (all p<0.05), but no differences compared with FIX. CONCLUSIONS: Continued individualized GH treatment after the catch-up growth period is safe and reduces hyperinsulinism. Individualized GH dose can be reduced once the desired height(SDS) is achieved to avoid overtreatment in terms of metabolic outcome.
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| 2. |
- Decker, Ralph, 1968, et al.
(författare)
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Metabolic outcome of GH treatment in prepubertal short children with and without classical GH deficiency
- 2010
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 73:3
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Tidskriftsartikel (refereegranskat)abstract
- Context: Few studies have evaluated the metabolic outcomes of growth hormone (GH) treatment in idiopathic short stature (ISS). Moreover, children with ISS appear to need higher GH doses than children with GH deficiency (GHD) to achieve the same amount of growth, and may therefore be at increased risk of adverse events during treatment. The individualized approach using prediction models for estimation of GH responsiveness, on the other hand, has the advantage of narrowing the range of growth response, avoiding too low or high GH doses. Design: Short prepubertal children with either isolated GHD (39) or ISS (89) participated in a 2-year randomized trial of either individualized GH treatment with six different GH doses (range, 17-100 mug/kg/day) or a standard dose (43 mug/kg/day). Objective: To evaluate if individualized GH treatment reduced the variance of the metabolic measures as shown for growth response, and to compare changes in metabolic variables in children with ISS and GHD. Hypothesis: Individualized GH dose reduces the range of metabolic outcomes, and metabolic outcomes are similar in children with ISS and GHD. Results: We observed a narrower variation for fasting insulin (-34.2%) and for HOMA (-38.9%) after two years of individualized GH treatment in comparison to standard GH dose treatment. Similar metabolic changes were seen in ISS and GHD. Delta (Delta) height SDS correlated with Deltainsulin-like growth factor I (IGF-I), Deltaleptin and Deltabody composition. Principal component analysis identified an anabolic and a lipolytic component. Anabolic variables [Deltalean body mass (LBM) SDS and DeltaIGF-I SDS] clustered together and correlated strongly with Deltaheight SDS and GH dose, whereas lipolytic variables [Deltafat mass SDS and Deltaleptin] were clustered separately from anabolic variables. Regression analysis showed GH dose-dependency in ISS, and to a lesser degree in GHD, for DeltaLBM SDS and Deltaheight SDS, but not for changes in fat mass. Conclusions: Individualized GH dosing during catch-up growth reduces the variance in insulin and HOMA and results in equal metabolic responses irrespective of the diagnosis of GHD or ISS.
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| 3. |
- Decker, Ralph, 1968, et al.
(författare)
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Protein markers predict body composition during growth hormone (GH) treatment in short prepubertal children.
- 2013
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 79:5, s. 675-82
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: A high-throughput pharmaco-proteomic approach has previously been successfully used to identify lipoprotein biomarkers related to changes in longitudinal growth and bone mass in response to growth hormone (GH) treatment. The aim of this study was to identify protein markers involved in the diverse anabolic and lipolytic remodelling of body composition during GH treatment. DESIGN, PATIENTS AND MEASUREMENTS: The study population consisted of 128 prepubertal children receiving GH treatment. Thirty-nine were short as a result of GH deficiency and 89 had idiopathic short stature (ISS). Serum protein expression profiles at study start and after one year of GH treatment were analysed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Body composition was analysed by dual-energy X-ray absorptiometry (DXA), reliably estimating muscle mass from appendicular (arms and legs) lean soft tissue mass (LST). DXA was also used to estimate appendicular bone mineral content (BMC) and fat mass for the total body. RESULTS: Specific protein expression patterns associated with GH response in different body compartments were identified. Among identified proteins different isoforms of nutrition markers such as apolipoproteins (Apo) were recognized; Apo C-I, Apo A-II, serum amyloid A4 (SAA4) and transthyretin (TTR). In addition, unidentified peaks were associated with GH effects on specific body compartments. CONCLUSIONS: Our results suggest that unique protein markers are associated with remodelling of different body compartments during GH treatment, which in the future might be useful to optimize GH treatment not only with regard to longitudinal growth. © 2013 Blackwell Publishing Ltd.
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