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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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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.

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Data Availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

OGTT:

2-h oral glucose tolerance test

ALT:

Aminotransaminase

BMI-SDS :

Body mass index standard deviation scores

ELISA:

Enzyme-linked immunosorbent assay

GGT:

Gamma-glutamyltransferase

GH:

Growth hormone

IGF-1:

Insulin-like growth factor-1

IGFBPs:

IGF-binding proteins

IGFBP-3:

IGF-binding protein-3

IR:

Insulin resistance

KIRA:

Kinase receptor activation

MAFLD:

Metabolic-associated fatty liver disease

NAFLD:

Non-alcoholic fatty liver disease

WLC:

Weight loss camp

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Acknowledgements

We thank the participants and the staff at Julemærkehjemmet Hobro for the collaboration during the study. Laboratory technician, Jane Hansen, Aarhus University Hospital, is thanked for helping drawing and processing all blood samples.

Funding

This work was supported by “Helsefonden, Denmark” and the Sanming Project of Medicine in Shenzhen (No. SZSM201612074) and Science and Technology Program of Shenzhen (No. JCYJ20190812164211151) of China.

Author information

Author notes

  1. David Haldrup and Chunshan Wei shared first co-authorship.

  2. Niels H. Birkebæk and Jan Frystyk shared last co-authorship.

Authors and Affiliations

  1. Department of Hepatology and Gastroenterology and Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

    David Haldrup, Chunshan Wei, Peter Holland-Fischer & Henning Grønbæk

  2. Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong Province, China

    Chunshan Wei

  3. Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark

    Peter Holland-Fischer

  4. Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aalborg, Denmark

    Kurt Kristensen, Søren Rittig, Aksel Lange & Niels H. Birkebæk

  5. Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

    Kurt Kristensen & Niels H. Birkebæk

  6. Department of Radiology, Aarhus University Hospital, Aarhus, Denmark

    Arne Hørlyck & Jan Solvig

  7. Department of Clinical Medicine, Health, Aarhus University, Aarhus, Denmark

    Jan Frystyk

  8. Department of Endocrinology, Odense University Hospital, Odense, Denmark

    Jan Frystyk

  9. Department of Clinical Research, Faculty of Health, University of Southern Denmark, Odense, Denmark

    Jan Frystyk

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  1. David Haldrup
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Contributions

CW, HG, NB, JF, AH, and JS designed the study and collected data. NB, HG, KK, SR, and AL performed consultations. PHF performed consultation and reference of statistics. CW, DH, NB, JF, and HG analyzed the children’s data. JF did the IGF and IGFBP-3 analysis. CW and DH wrote the manuscript draft. JF supervised manuscript writing. All authors contributed important intellectual content and critically revised the manuscript. All authors reviewed the manuscript and approved the final version.

Corresponding author

Correspondence to David Haldrup.

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The authors declare no competing interests.

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Communicated by Gregorio Milani

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Haldrup, D., Wei, C., Holland-Fischer, P. et al. Effects of lifestyle intervention on IGF-1, IGFBP-3, and insulin resistance in children with obesity with or without metabolic-associated fatty liver disease. Eur J Pediatr 182, 855–865 (2023). https://doi.org/10.1007/s00431-022-04731-1

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