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- Jensen, Rikke Beck, et al.
(författare)
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A randomised controlled trial evaluating IGF-I titration in contrast to current GH dosing strategies in children born Small for Gestational Age (NESGAS).
- 2014
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 171:4, s. 509-518
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Tidskriftsartikel (refereegranskat)abstract
- Background: Short children born small for gestational age (SGA) are treated with growth hormone (GH) dose based on body size, but treatment may lead to high levels of IGF-I. The objective was to evaluate IGF-I titration of GH dose in contrast to current dosing strategies. Methods: In the North European Small for gestational age study (NESGAS) 92 short pre-pubertal children born SGA were randomised after one year of high dose GH treatment (67µg/kg/day) to three different regimens: high-dose (67µg/kg/day), low-dose (35µg/kg/day) or IGF-I titration. Results: The average dose during the second year of the randomised trial did not differ between the IGF-I titration group (38µg/kg/day, SD 0.019) and the low-dose group (35µg/kg/day, SD 0.002) (P=0•46), but there was a wide variation in the IGF-I titration group (range 10-80µg/kg/day). The IGF-I titration group had significantly lower height gain (0.17SDS, SD 0.18) during the second year of the randomised trial compared to the high-dose group (0.46SDS, SD 0.25) but not significantly lower than the low-dose group (0.23SDS, SD 0.15) (p=0.17). The IGF-I titration group had lower IGF-I levels after two years of the trial (mean 1.16, SD 1.24) compared to both the low-dose (mean 1.76, SD 1.48) and the high-dose (mean 2.97, SD 1.63) groups. Conclusion: IGF-I titration of GH dose in SGA children proved less effective than current dosing strategies. IGF-I titration resulted in physiological IGF-I levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF-I resistance and highlights the heterogeneity of short SGA children.
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| 2. |
- Jensen, Rikke Beck, et al.
(författare)
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Baseline IGF-I Levels Determine Insulin Secretion and Insulin Sensitivity during the First Year on Growth Hormone Therapy in Children Born Small for Gestational Age. Results from a North European Multicentre Study (NESGAS)
- 2013
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Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 80:1, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Developmental programming alters growth and metabolic outcome in children born small for gestational age (SGA). We explored insulin and glucose metabolism in SGA children treated with a fixed GH dose over 1 year. Methods: In the North European Small for Gestational Age Study (NESGAS), 110 short SGA children received GH at 67 mu g/kg/day for 1 year. Insulin secretion was assessed by acute insulin response (AIR), insulin sensitivity (IS) by HOMA and disposition index (DI) by insulin secretion adjusted for IS. Results: First-year GH therapy led to increases in height and IGF-I standard deviation score (SDS), and reductions in IS (p < 0.0001). Compensatory increases in AIR (p < 0.0001) were insufficient and resulted in reduced DI (p = 0.032). Children in the highest IGF-I SDS tertile at baseline were the least insulin sensitive at baseline (p = 0.024) and 1 year (p = 0.006). IGF-I responses after 1 year were positively related to AIR (r = 0.30, p = 0.007) and DI (r = 0.29, p = 0.005). Conclusion: In SGA children treated with a high GH dose for 1 year, baseline IGF-I levels were related to IS whilst gains in height and IGF-I responses were associated with insulin secretion. Defining heterogeneity in IGF-I in SGA children may be useful in predicting growth and metabolic response. Copyright (C) 2013 S. Karger AG, Basel
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| 3. |
- Jensen, Rikke Beck, et al.
(författare)
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Genetic Markers of Insulin Sensitivity and Insulin Secretion Are Associated With Spontaneous Postnatal Growth and Response to Growth Hormone Treatment in Short SGA Children: the North European SGA Study (NESGAS)
- 2015
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:3, s. 503-507
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The wide heterogeneity in the early growth and metabolism of children born small for gestational age (SGA), both before and during GH therapy, may reflect common genetic variations related to insulin secretion or sensitivity. Method: Combined multiallele single nucleotide polymorphism scores with known associations with insulin sensitivity or insulin secretion were analyzed for their relationships with spontaneous postnatal growth and first-year responses to GH therapy in 96 short SGA children. Results: The insulin sensitivity allele score (GS-InSens) was positively associated with spontaneous postnatal weight gain (regression coefficient [B]: 0.12 SD scores per allele; 95% confidence interval [CI], 0.01-0.23; P = .03) and also in response to GH therapy with first-year height velocity (B: 0.18 cm/y per allele; 95% CI, 0.02-0.35; P = .03) and change in IGF-1 (B: 0.17 SD scores per allele; 95% CI, 0.00-0.32; P = .03). The association with first-year height velocity was independent of reported predictors of response to GH therapy (adjusted P = .04). The insulin secretion allele score (GS-InSec) was positively associated with spontaneous postnatal height gain (B: 0.15; 95% CI, 0.01-0.30; P = .03) and disposition index both before (B: 0.02; 95% CI, 0.00-0.04; P = .04) and after 1 year of GH therapy (B: 0.03; 95% CI, 0.01-0.05; P = .002), but not with growth and IGF-1 responses to GH therapy. Neither of the allele scores was associated with size at birth. Conclusion: Genetic allele scores indicative of insulin sensitivity and insulin secretion were associated with spontaneous postnatal growth and responses to GH therapy in short SGA children. Further pharmacogenetic studies may support the rationale for adjuvant therapies by informing the mechanisms of treatment response.
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| 7. |
- Upners, Emmie N., et al.
(författare)
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Timing of Puberty, Pubertal Growth, and Adult Height in Short Children Born Small for Gestational Age Treated With Growth Hormone
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:8, s. 2286-2295
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Tidskriftsartikel (refereegranskat)abstract
- Context: Growth hormone (GH) is used to treat short children born small for gestational age (SGA); however, the effects of treatment on pubertal timing and adult height are rarely studied. Objective: To evaluate adult height and peak height velocity in short GH-treated SGA children. Methods: Prospective longitudinal multicenter study. Participants were short children born SGA treated with GH therapy (n = 102). Adult height was reported in 47 children. A reference cohort of Danish children was used. Main outcome measures were adult height, peak height velocity, age at peak height, and pubertal onset. Pubertal onset was converted to SD score (SDS) using Danish reference data. Results: Gain in height SDS from start of treatment until adult height was significant in both girls (0.94 [0.75; 1.53] SDS, P = .02) and boys (1.57 [1.13; 2.15] SDS, P < .001). No difference in adult height between GH dosage groups was observed. Peak height velocity was lower than a reference cohort for girls (6.5 [5.9; 7.6] cm/year vs 7.9 [7.4; 8.5] cm/year, P < .001) and boys (9.5 [8.4; 10.7] cm/year vs 10.1 [9.7; 10.7] cm/year, P = .002), but no difference in age at peak height velocity was seen. Puberty onset was earlier in SGA boys than a reference cohort (1.06 [-0.03; 1.96] SDS vs 0 SDS, P = .002) but not in girls (0.38 [-0.19; 1.05] SDS vs 0 SDS, P = .18). Conclusion: GH treatment improved adult height. Peak height velocity was reduced, but age at peak height velocity did not differ compared with the reference cohort. SGA boys had an earlier pubertal onset compared with the reference cohort.
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