Effect of Time-Restricted Eating on Circulating Levels of IGF1 and Its Binding Proteins in Obesity: An Exploratory Analysis of a Randomized Controlled Trial

Abstract

Obesity is associated with alterations in circulating IGF1, IGF1-binding proteins (IGFBPs), insulin, inflammatory markers, and hormones implicated in cardiovascular disease, diabetes, cancer, and aging. However, the effects of 4 and 6 h time-restricted eating (TRE) on circulating IGF1 and IGFBPs is uncertain.

Objective: This study aimed to investigate the effects of TRE on plasma IGF1, IGFBP1, IGFBP2, and IGFBP3, and whether these effects were mediated by weight loss or body composition changes. Insulin sensitivity, glucose control, adipokines, and inflammatory markers were also examined.

Design: An exploratory analysis of an 8-week randomized controlled trial implementing a daily TRE intervention was carried out.

Participants/setting: This study was conducted at the University of Illinois at Chicago in 2019. Participants with obesity were randomized to 4 or 6 h TRE (n = 35) or a control (n = 14) group. Plasma biomarkers were measured by ELISA at baseline and week 8. In a sub-analysis, participants were stratified into higher- (>3.5%) and lower- (≤3.5%) weight-loss groups.

Intervention: Participants fasted daily from 7 p.m. to 3 p.m. in the 4 h TRE group (20 h) and from 7 p.m. to 1 p.m. in the 6 h TRE group (18 h), followed by ad libitum eating for the remainder of the day. Controls received no dietary recommendations.

Main outcome measures: IGF1, IGFBPs, hsCRP, and adipokines were the main outcome measures of this analysis.

Statistical analysis: Repeated measures ANOVA and mediation analysis were conducted.

Results: Body weight significantly decreased with TRE (-3.6 ± 0.3%), contrasting with controls (+0.2 ± 0.5%, p < 0.001). Significant effects of TRE over time were observed on plasma IGFBP2, insulin, HOMA-IR, and 8-isoprostane levels, without affecting other biomarkers. In the sub-analysis, IGFBP2 increased while leptin and 8-isoprostane decreased significantly only in the "higher weight loss" subgroup. Changes in insulin and HOMA-IR were related to TRE adherence.

Conclusions: Eight-week daily 4 to 6 h TRE did not affect IGF1, IGFBP1, or IGFBP3 levels but improved insulin, HOMA-IR, and 8-isoprostane. IGFBP2 increased and leptin decreased when weight loss exceeded 3.5% of baseline.

Keywords: IGF1; IGFBP; growth hormones; insulin; intermittent fasting; obesity.

Figure 1

Percentage of weight loss relative to baseline, stratified according to final weight loss percentage (lower vs. higher) over 8 weeks of time-restricted eating intervention. Data are expressed as mean ± SEM for percentage of weight loss (WL%) relative to baseline body weight. Participants were stratified into lower WL% (≤3.5%, n = 29) and higher WL% (>3.5%, n = 20). * p < 0.05 and *** p < 0.001 for mean weight loss percentage in a specific week vs. group-matched baseline.

Figure 2

Weight loss as a mediator of the effects of TRE on IGFBP2, 8-isoprostane, insulin, and HOMA-IR. Mediation models presenting (A) weight loss as a mediator of the increase in serum IGFBP2 and the decrease in serum 8-isoprostane levels induced by TRE; (B) weight loss as a mediator of the decrease in serum insulin and HOMA-IR induced by TRE, and the reversed model where the reduction in serum insulin or HOMA-IR mediate the effect of TRE on weight loss; and (C) fat mass loss as mediator of the decrease in serum leptin and the increase in high-molecular-weight adiponectin induced by TRE. The indirect effects of all these models were not significant, suggesting no mediation. IGFBP2: insulin-like growth factor 2; HOMA-IR: homeostatic model assessment of insulin resistance.