Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease

David Haldrup; Chunshan Wei; Peter Holland-Fischer; Kurt Kristensen; Søren Rittig; Aksel Lange; Arne Hørlyck; Jan Solvig; Henning Grønbæk; Niels H Birkebæk; Jan Frystyk

doi:10.1007/s00431-022-04731-1

Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease

David Haldrup, Chunshan Wei, Peter Holland-Fischer, Kurt Kristensen, Søren Rittig, Aksel Lange, Arne Hørlyck, Jan Solvig, Henning Grønbæk, Niels H Birkebæk, Jan Frystyk

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Obesity is a strong predictor for metabolic associated fatty liver disease (MAFLD), which has been associated with decreased insulin like growth factor 1 (IGF-1). In obesity, weight loss increases growth hormone secretion, but this is not unequivocally associated with increases in serum IGF-1 and IGF binding protein-3 (IGFBP-3). We studied the changes in the IGF axis in relation to weight loss and improvement in insulin resistance in children with or without MALFD after 10 weeks of lifestyle intervention at a weight loss camp (WLC). We investigated 113 (66 females) Caucasian children with obesity, median age 12.4 (range 7.3-14.6) years, before and after 10 weeks of lifestyle intervention at a WLC. We investigated children who was either MAFLD positive (n = 54) or negative (n = 59) before and after WLC. Children with MAFLD had lower baseline IGF-1 (249 ± 112 vs 278 ± 107 µg/l, P = 0.048), whereas the IGF-1/IGFBP-3 molar ratio was similar to children without MAFLD (19.4 ± 6.6 vs. 21.8 ± 6.6%, P = 0.108). When all children were considered as one group, WLC decreased SDS-BMI and HOMA-IR (P < 0.001, both) and increased IGF-1 (264 ± 110 vs 285 ± 108 µg/l, P < 0.001) and the IGF/IGFBP-3 molar ratio (20.7 ± 6.7 vs 22.4 ± 6.1%, P < 0.001). When categorized according to liver status, IGF-1 increased significantly in children with MAFLD (P = 0.008) and tended to increase in children without MAFLD (P = 0.052). Conclusions: Ten weeks of lifestyle intervention decreased insulin resistance and improved the IGF axis. We observed slight differences in the IGF axis in relation to MAFLD status. This suggests that the IGF axis is primarily influenced by insulin resistance rather than MAFLD status. What is New: • Weight loss decreases insulin resistance and subsequently increases the IGF axis in children with obesity. • Children with MAFLD had an aberration in the IGF axis compared to their MAFLD negative counter parts and the IGF axis was primarily influenced by the decreased BMI-SDS and insulin resistance, rather than MAFLD status. What is Known: • NAFLD has previously been associated with reduced serum IGF-1 concentrations. • Data on the impact of MAFLD and aberrations in the growth hormone and IGF axis and the effects of lifestyle interventions in children are limited.

Original language	English
Journal	European Journal of Pediatrics
Volume	182
Issue	2
Pages (from-to)	855–865
Number of pages	11
ISSN	0340-6199
DOIs	https://doi.org/10.1007/s00431-022-04731-1
Publication status	Published - Feb 2023

Keywords

Children
Insulin-like growth factor axis
Lifestyle intervention
Metabolic-associated fatty liver disease
Obesity

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10.1007/s00431-022-04731-1

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Haldrup, D., Wei, C., Holland-Fischer, P., Kristensen, K., Rittig, S., Lange, A., Hørlyck, A., Solvig, J., Grønbæk, H., Birkebæk, N. H., & Frystyk, J. (2023). Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease. European Journal of Pediatrics, 182(2), 855–865. https://doi.org/10.1007/s00431-022-04731-1

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title = "Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease",

abstract = "Obesity is a strong predictor for metabolic associated fatty liver disease (MAFLD), which has been associated with decreased insulin like growth factor 1 (IGF-1). In obesity, weight loss increases growth hormone secretion, but this is not unequivocally associated with increases in serum IGF-1 and IGF binding protein-3 (IGFBP-3). We studied the changes in the IGF axis in relation to weight loss and improvement in insulin resistance in children with or without MALFD after 10 weeks of lifestyle intervention at a weight loss camp (WLC). We investigated 113 (66 females) Caucasian children with obesity, median age 12.4 (range 7.3-14.6) years, before and after 10 weeks of lifestyle intervention at a WLC. We investigated children who was either MAFLD positive (n = 54) or negative (n = 59) before and after WLC. Children with MAFLD had lower baseline IGF-1 (249 ± 112 vs 278 ± 107 µg/l, P = 0.048), whereas the IGF-1/IGFBP-3 molar ratio was similar to children without MAFLD (19.4 ± 6.6 vs. 21.8 ± 6.6%, P = 0.108). When all children were considered as one group, WLC decreased SDS-BMI and HOMA-IR (P < 0.001, both) and increased IGF-1 (264 ± 110 vs 285 ± 108 µg/l, P < 0.001) and the IGF/IGFBP-3 molar ratio (20.7 ± 6.7 vs 22.4 ± 6.1%, P < 0.001). When categorized according to liver status, IGF-1 increased significantly in children with MAFLD (P = 0.008) and tended to increase in children without MAFLD (P = 0.052). Conclusions: Ten weeks of lifestyle intervention decreased insulin resistance and improved the IGF axis. We observed slight differences in the IGF axis in relation to MAFLD status. This suggests that the IGF axis is primarily influenced by insulin resistance rather than MAFLD status. What is New: • Weight loss decreases insulin resistance and subsequently increases the IGF axis in children with obesity. • Children with MAFLD had an aberration in the IGF axis compared to their MAFLD negative counter parts and the IGF axis was primarily influenced by the decreased BMI-SDS and insulin resistance, rather than MAFLD status. What is Known: • NAFLD has previously been associated with reduced serum IGF-1 concentrations. • Data on the impact of MAFLD and aberrations in the growth hormone and IGF axis and the effects of lifestyle interventions in children are limited.",

keywords = "Children, Insulin-like growth factor axis, Lifestyle intervention, Metabolic-associated fatty liver disease, Obesity",

author = "David Haldrup and Chunshan Wei and Peter Holland-Fischer and Kurt Kristensen and S{\o}ren Rittig and Aksel Lange and Arne H{\o}rlyck and Jan Solvig and Henning Gr{\o}nb{\ae}k and Birkeb{\ae}k, {Niels H} and Jan Frystyk",

note = "{\textcopyright} 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2023",

month = feb,

doi = "10.1007/s00431-022-04731-1",

language = "English",

volume = "182",

pages = "855–865",

journal = "European Journal of Pediatrics",

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Haldrup, D, Wei, C, Holland-Fischer, P, Kristensen, K , Rittig, S , Lange, A, Hørlyck, A, Solvig, J, Grønbæk, H , Birkebæk, NH & Frystyk, J 2023, 'Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease', European Journal of Pediatrics, vol. 182, no. 2, pp. 855–865. https://doi.org/10.1007/s00431-022-04731-1

Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease. / Haldrup, David; Wei, Chunshan; Holland-Fischer, Peter et al.
In: European Journal of Pediatrics, Vol. 182, No. 2, 02.2023, p. 855–865.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease

AU - Haldrup, David

AU - Wei, Chunshan

AU - Holland-Fischer, Peter

AU - Kristensen, Kurt

AU - Rittig, Søren

AU - Lange, Aksel

AU - Hørlyck, Arne

AU - Solvig, Jan

AU - Grønbæk, Henning

AU - Birkebæk, Niels H

AU - Frystyk, Jan

PY - 2023/2

Y1 - 2023/2

N2 - Obesity is a strong predictor for metabolic associated fatty liver disease (MAFLD), which has been associated with decreased insulin like growth factor 1 (IGF-1). In obesity, weight loss increases growth hormone secretion, but this is not unequivocally associated with increases in serum IGF-1 and IGF binding protein-3 (IGFBP-3). We studied the changes in the IGF axis in relation to weight loss and improvement in insulin resistance in children with or without MALFD after 10 weeks of lifestyle intervention at a weight loss camp (WLC). We investigated 113 (66 females) Caucasian children with obesity, median age 12.4 (range 7.3-14.6) years, before and after 10 weeks of lifestyle intervention at a WLC. We investigated children who was either MAFLD positive (n = 54) or negative (n = 59) before and after WLC. Children with MAFLD had lower baseline IGF-1 (249 ± 112 vs 278 ± 107 µg/l, P = 0.048), whereas the IGF-1/IGFBP-3 molar ratio was similar to children without MAFLD (19.4 ± 6.6 vs. 21.8 ± 6.6%, P = 0.108). When all children were considered as one group, WLC decreased SDS-BMI and HOMA-IR (P < 0.001, both) and increased IGF-1 (264 ± 110 vs 285 ± 108 µg/l, P < 0.001) and the IGF/IGFBP-3 molar ratio (20.7 ± 6.7 vs 22.4 ± 6.1%, P < 0.001). When categorized according to liver status, IGF-1 increased significantly in children with MAFLD (P = 0.008) and tended to increase in children without MAFLD (P = 0.052). Conclusions: Ten weeks of lifestyle intervention decreased insulin resistance and improved the IGF axis. We observed slight differences in the IGF axis in relation to MAFLD status. This suggests that the IGF axis is primarily influenced by insulin resistance rather than MAFLD status. What is New: • Weight loss decreases insulin resistance and subsequently increases the IGF axis in children with obesity. • Children with MAFLD had an aberration in the IGF axis compared to their MAFLD negative counter parts and the IGF axis was primarily influenced by the decreased BMI-SDS and insulin resistance, rather than MAFLD status. What is Known: • NAFLD has previously been associated with reduced serum IGF-1 concentrations. • Data on the impact of MAFLD and aberrations in the growth hormone and IGF axis and the effects of lifestyle interventions in children are limited.

AB - Obesity is a strong predictor for metabolic associated fatty liver disease (MAFLD), which has been associated with decreased insulin like growth factor 1 (IGF-1). In obesity, weight loss increases growth hormone secretion, but this is not unequivocally associated with increases in serum IGF-1 and IGF binding protein-3 (IGFBP-3). We studied the changes in the IGF axis in relation to weight loss and improvement in insulin resistance in children with or without MALFD after 10 weeks of lifestyle intervention at a weight loss camp (WLC). We investigated 113 (66 females) Caucasian children with obesity, median age 12.4 (range 7.3-14.6) years, before and after 10 weeks of lifestyle intervention at a WLC. We investigated children who was either MAFLD positive (n = 54) or negative (n = 59) before and after WLC. Children with MAFLD had lower baseline IGF-1 (249 ± 112 vs 278 ± 107 µg/l, P = 0.048), whereas the IGF-1/IGFBP-3 molar ratio was similar to children without MAFLD (19.4 ± 6.6 vs. 21.8 ± 6.6%, P = 0.108). When all children were considered as one group, WLC decreased SDS-BMI and HOMA-IR (P < 0.001, both) and increased IGF-1 (264 ± 110 vs 285 ± 108 µg/l, P < 0.001) and the IGF/IGFBP-3 molar ratio (20.7 ± 6.7 vs 22.4 ± 6.1%, P < 0.001). When categorized according to liver status, IGF-1 increased significantly in children with MAFLD (P = 0.008) and tended to increase in children without MAFLD (P = 0.052). Conclusions: Ten weeks of lifestyle intervention decreased insulin resistance and improved the IGF axis. We observed slight differences in the IGF axis in relation to MAFLD status. This suggests that the IGF axis is primarily influenced by insulin resistance rather than MAFLD status. What is New: • Weight loss decreases insulin resistance and subsequently increases the IGF axis in children with obesity. • Children with MAFLD had an aberration in the IGF axis compared to their MAFLD negative counter parts and the IGF axis was primarily influenced by the decreased BMI-SDS and insulin resistance, rather than MAFLD status. What is Known: • NAFLD has previously been associated with reduced serum IGF-1 concentrations. • Data on the impact of MAFLD and aberrations in the growth hormone and IGF axis and the effects of lifestyle interventions in children are limited.

KW - Children

KW - Insulin-like growth factor axis

KW - Lifestyle intervention

KW - Metabolic-associated fatty liver disease

KW - Obesity

U2 - 10.1007/s00431-022-04731-1

DO - 10.1007/s00431-022-04731-1

M3 - Journal article

C2 - 36508014

SN - 0340-6199

VL - 182

SP - 855

EP - 865

JO - European Journal of Pediatrics

JF - European Journal of Pediatrics

IS - 2

ER -

Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease

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Keywords

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