Serum IGF1 and linear growth in children with congenital leptin deficiency before and after leptin substitution

Marianna Beghini, Stephanie Brandt, Ingrid Körber, Katja Kohlsdorf, Heike Vollbach, Belinda Lennerz, Christian Denzer, Shlomit Shalitin, Ferruccio Santini, Werner F. Blum, Julia von Schnurbein, Martin Wabitsch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Evidence from in vitro and rodent studies suggests that leptin, a key signal of long-term energy reserves, promotes IGF1 synthesis and linear growth. This effect of leptin has not been fully investigated in humans. The aim of our study was to investigate the effect of leptin substitution on growth factors and linear growth in children with congenital leptin deficiency (CLD). Methods: In this cohort study we included eight pediatric patients (six males), age 0.9–14.8 years, who were diagnosed with CLD and received leptin substitution at our University Medical Center. We calculated standard deviation scores (SDS) for serum levels of IGF1 and IGFBP3, IGF1/IGFBP3 molar ratio, and height at baseline (T0) and 12 months (T12) after the initiation of substitution with metreleptin. Results: All patients had severe obesity (BMI-SDS mean ± SD: 4.14 ± 1.51) at T0 and significant BMI-SDS reduction to 2.47 ± 1.05 at T12. At T0, all patients were taller than the mid-parental median, yet had low IGF1 and IGF1/IGFBP3 molar ratios (IGF1-SDSx¯ T0: −1.58 ± 0.92, IGF1/IGFBP3 molar ratio-SDSx¯ T0: −1.58 ± 0.88). At T12, IGF1-SDS increased significantly (∆T0–12: 1.63 ± 1.40, p = 0.01), and IGFBP3-SDS and IGF1/IGFBP3 molar ratio-SDS showed a trend toward an increase. In the three children within the childhood growth period (post-infancy, pre-puberty) height-SDS increased (∆height-SDST0–12: 0.57 ± 0.06, p = 0.003) despite substantial weight loss. Conclusions: These results in CLD patients are contrary to observations in children with idiopathic obesity who typically have above-mean IGF1 levels that decrease with weight loss, and therefore suggest that leptin increases IGF1 levels and promotes linear growth.

Original languageEnglish
Pages (from-to)1448-1456
Number of pages9
JournalInternational Journal of Obesity
Issue number7
StatePublished - Jul 2021


FundersFunder number
Obesity and Lipodystrophy Center
Bundesministerium für Bildung und Forschung01GI1120A/B
Universität UlmKSKI 002.1, LSSH1000.07
Hexal AG


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