IGFBP-1 and IGF-I in relation to adiposity and mortality from midlife to old age in the Swedish Adoption/Twin Study of Aging

• DOI: 10.1038/s41366-025-01773-x
• Publication Date: 2025-04-05T10:33:18Z
• Authors: Moira S. Lewitt; Ida K. Karlsson; Nancy L. Pedersen

Abstract

Background/Objectives Insulin-like growth factor-binding protein (IGFBP)-1 is a marker of insulin resistance. Lower IGFBP-1 is associated with increased adiposity. The aims of this study were to determine whether IGFBP-1 and its ligand, IGF-I, are associated with weight and waist measurements across mid-life to old age, and predict survival.

Subjects/Methods The Swedish Adoption/Twin Study of Aging (SATSA) includes extensive in-person testing of same-sex twins over a 30-year period. The dataset of twins for which baseline fasting IGFBP-1 (n = 512; 251 twin pairs) and IGF-I (n = 537; 262 twin pairs) measurements were available (from 1986) was stratified by birth cohort. Latent growth curve modeling was used to determine whether BMI and waist-to-height ratio (WHtR) and their change, differed as a function of IGFBP-1 or IGF-I. Survival data was collected by linkage to the Swedish Tax Agency.

Results IGFBP-1 correlated inversely with insulin concentrations. There was a curvilinear relationship between BMI and age, increasing until 70–75 years and then declining, fitting a quadratic model. Lower IGFBP-1 was associated with higher BMI at the intercept, 73 years (1.8 kg/m2 per unit decrease in ln-IGFBP-1; p < 0.001). WHtR continued to increase beyond 70–75 years. Lower IGFBP-1 was associated with higher WHtR (3 cm/m per unit decrease in ln-IGFBP-1 at 73 years; p < 0.001). Associations weakened, but remained, after adjustment for ln-insulin. IGFBP-1 was not associated with the slope or shape of the trajectories. Between-within models, examining the associations within twin pairs, indicated these associations are explained in part by familial factors. There was no relationship between IGF-I and BMI or WHtR, or their trajectories. Neither IGFBP-1 nor IGF-I concentration predicted survival.

Conclusion Lower circulating IGFBP-1 concentrations are associated with increased adiposity but not change in adiposity, across the lifespan from middle to old age.