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)

Rikke Beck Jensen; Ajay Thankamony; Felix Day; Robert A Scott; Claudia Langenberg; Jeremy Kirk; Malcolm Donaldson; Sten-A Ivarsson; Olle Söder; Edna Roche; Hilary Hoey; Anders Juul; Ken K Ong; David B Dunger

doi:10.1210/jc.2014-3469

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)

Rikke Beck Jensen, Ajay Thankamony, Felix Day, Robert A Scott, Claudia Langenberg, Jeremy Kirk, Malcolm Donaldson, Sten-A Ivarsson, Olle Söder, Edna Roche, Hilary Hoey, Anders Juul, Ken K Ong, David B Dunger

Department of Clinical Medicine

9 Citations (Scopus)

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.

Original language	English
Journal	Endocrinology
Volume	100
Issue number	3
Pages (from-to)	E503–E507
Number of pages	5
ISSN	0013-7227
DOIs	https://doi.org/10.1210/jc.2014-3469
Publication status	Published - 1 Mar 2015

Keywords

Body Height
Child Development
Europe
Female
Genetic Markers
Growth Disorders
Human Growth Hormone
Humans
Infant, Newborn
Infant, Small for Gestational Age
Insulin
Insulin Resistance
Male
Treatment Outcome

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Jensen, R. B., Thankamony, A., Day, F., Scott, R. A., Langenberg, C., Kirk, J., Donaldson, M., Ivarsson, S-A., Söder, O., Roche, E., Hoey, H., Juul, A., Ong, K. K., & Dunger, D. B. (2015). 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). Endocrinology, 100(3), E503–E507. https://doi.org/10.1210/jc.2014-3469

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). / Jensen, Rikke Beck; Thankamony, Ajay; Day, Felix et al.

In: Endocrinology, Vol. 100, No. 3, 01.03.2015, p. E503–E507.

Research output: Contribution to journal › Journal article › Research › peer-review

Jensen, RB, Thankamony, A, Day, F, Scott, RA, Langenberg, C, Kirk, J, Donaldson, M, Ivarsson, S-A, Söder, O, Roche, E, Hoey, H, Juul, A, Ong, KK & Dunger, DB 2015, '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)', Endocrinology, vol. 100, no. 3, pp. E503–E507. https://doi.org/10.1210/jc.2014-3469

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title = "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)",

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.",

keywords = "Body Height, Child Development, Europe, Female, Genetic Markers, Growth Disorders, Human Growth Hormone, Humans, Infant, Newborn, Infant, Small for Gestational Age, Insulin, Insulin Resistance, Male, Treatment Outcome",

author = "Jensen, {Rikke Beck} and Ajay Thankamony and Felix Day and Scott, {Robert A} and Claudia Langenberg and Jeremy Kirk and Malcolm Donaldson and Sten-A Ivarsson and Olle S{\"o}der and Edna Roche and Hilary Hoey and Anders Juul and Ong, {Ken K} and Dunger, {David B}",

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T1 - Genetic Markers of Insulin Sensitivity and Insulin Secretion Are Associated With Spontaneous Postnatal Growth and Response to Growth Hormone Treatment in Short SGA Children

T2 - the North European SGA Study (NESGAS)

AU - Jensen, Rikke Beck

AU - Thankamony, Ajay

AU - Day, Felix

AU - Scott, Robert A

AU - Langenberg, Claudia

AU - Kirk, Jeremy

AU - Donaldson, Malcolm

AU - Ivarsson, Sten-A

AU - Söder, Olle

AU - Roche, Edna

AU - Hoey, Hilary

AU - Juul, Anders

AU - Ong, Ken K

AU - Dunger, David B

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

KW - Body Height

KW - Child Development

KW - Europe

KW - Female

KW - Genetic Markers

KW - Growth Disorders

KW - Human Growth Hormone

KW - Humans

KW - Infant, Newborn

KW - Infant, Small for Gestational Age

KW - Insulin

KW - Insulin Resistance

KW - Male

KW - Treatment Outcome

U2 - 10.1210/jc.2014-3469

DO - 10.1210/jc.2014-3469

M3 - Journal article

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SN - 0013-7227

VL - 100

SP - E503–E507

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

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