Trajectories of body fatness from age 5 to 60 y and plasma biomarker concentrations of the insulin–insulin-like growth factor system

Abstract

Abstract Background A major pathway through which obesity increases the risk of cardiometabolic diseases and cancer is by inducing hormonal and metabolic abnormalities, including hyperinsulinemia and altered insulin-like growth factor (IGF) signaling. However, little is known about the influence of lifetime adiposity on the relevant biomarkers. Objective The aim of this study was to examine associations of trajectories of body fatness with plasma biomarker concentrations of the insulin-IGF system in 2 large prospective cohorts of US men and women. Design Associations between trajectories of body fatness and concentrations of plasma C-peptide, IGF-I, IGF-binding protein (IGFBP) 1, IGFBP-3, and the IGF-I–to–IGFBP-3 molar ratio was examined in 9386 women of the Nurses’ Health Study and 3941 men of the Health Professionals Follow-Up Study. Group-based trajectory modeling was used to create trajectory groups on the basis of self-reported somatotype data at ages 5, 10, 20, 30, and 40 y and body mass index (BMI) at ages 45, 50, 55, and 60 y. We used multivariate linear regression models to examine the associations of trajectories with biomarker concentrations. Results Five trajectories of body fatness were identified: “lean-stable,” “lean–moderate increase,” “lean–marked increase,” “medium-stable/increase,” and “medium–marked increase.” Compared with the lean-stable group, the lean–marked increase and medium–marked increase groups had significantly higher concentrations of C-peptide (percentage difference—women: 44% and 73%; men: 27% and 51%) and lower concentrations of IGFBP-1 (women: –61% and –78%; men: –47% and –65%). Adjustment for current BMI attenuated the association to null for the medium–marked increase group, but the lean–marked increase group still had modestly higher concentrations of C-peptide (women: 10%; men: 6%) and lower concentrations of IGFBP-1 (women: –18%; men: –21%) than the lean-stable group. Conclusions Adiposity across the life span was associated with higher C-peptide and lower IGFBP-1 concentrations in adulthood. The associations were largely driven by attained adiposity and, to a lesser extent, weight gain in early-middle adulthood. This trial was registered at www.clinicaltrials.gov as NCT03419455.