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.