BMI and Contraceptives Affect New Age-, Sex-, and Puberty-adjusted IGF-I and IGFBP-3 Reference Ranges Across Life Span

J Clin Endocrinol Metab. 2022 Jun 16;107(7):e2991-e3002. doi: 10.1210/clinem/dgac157.

Abstract

Context: Various clinical factors influencing serum levels of insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are not entirely consistently described.

Objective: We asked whether body mass index (BMI), contraceptive drugs (CDs), and hormone replacement therapy (HRT) have potential effects on data for interpreting new age-, sex-, and puberty-adjusted reference ranges for IGF-I and IGFBP-3 serum levels.

Design and setting: Subjects were mainly participants from 2 population-based cohort studies: the LIFE Child study of children and adolescents and the LIFE Adult study.

Participants: We investigated 9400 serum samples from more than 7000 healthy and 1278 obese subjects between 3 months and 81 years old.

Main outcome measures: Associations between IGF-I or IGFBP-3, measured with a new electrochemiluminescence immunoassay, and the predictors BMI and CDs were estimated using hierarchical linear modeling.

Results: During infancy, obese children had up to 1 SD score (SDS) higher mean predicted IGF-I values, converging with levels of normal-weight subjects up to 13 years old. Between 20 and 40 years of age, obesity was related to up to -0.5 lower IGF-I SDS values than the predicted values. Obesity had less impact on IGFBP-3. Estrogen- and progestin-based CDs, but not HRT, decreased IGF-I and increased IGFBP-3 (P < 0.01) in adolescents (β IGF-I = -0.45, β IGFBP-3 = 0.94) and adults (β IGF-I = -0.43, β IGFBP-3 = 1.12). Conversely, progestin-based CDs were significantly positive associated with IGF-I (β IGF-I =0.82).

Conclusions: BMI and CDs must be considered when assessing and interpreting the clinical relevance of IGF-I and IGFBP-3 measurements.

Keywords: BMI; IGF-I; IGFBP-3; contraceptive drugs; obesity; reference ranges.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index*
  • Child
  • Child, Preschool
  • Contraceptive Agents*
  • Humans
  • Infant
  • Insulin-Like Growth Factor Binding Protein 3* / blood
  • Insulin-Like Growth Factor I* / metabolism
  • Longevity
  • Middle Aged
  • Pediatric Obesity
  • Progestins
  • Puberty
  • Reference Values
  • Young Adult

Substances

  • Contraceptive Agents
  • Insulin-Like Growth Factor Binding Protein 3
  • Progestins
  • Insulin-Like Growth Factor I

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