Effects of Dietary Weight Loss and Exercise on Insulin-Like Growth Factor-I and Insulin-Like Growth Factor-Binding Protein-3 in Postmenopausal Women: A Randomized Controlled Trial

Abstract

High levels of insulin-like growth factor (IGF)-1 may increase the risk of common cancers in humans. We hypothesized that weight loss induced by diet and/or exercise would reduce IGF-1 in postmenopausal women. Four hundred and thirty nine overweight or obese (BMI ≥25kg/m2) women (50–75 y) were randomly assigned to: i) exercise (N=117), ii) dietary weight-loss (N=118), iii) diet + exercise (N=117), or iv) control (n=87). The diet intervention was a group-based program with a 10% weight loss goal. The exercise intervention was 45 min/day, 5 days/week of moderate-to-vigorous intensity activity. Fasting serum insulin-like growth factor (IGF)-1 and insulin-like growth factor binding protein (IGFBP)-3 were measured at baseline and 12 months by radioimmunoassay. Higher baseline BMI was associated with lower IGF-1 and IGF-1/IGFBP-3 molar ratio. While no significant changes in either IGF-1 or IGFBP-3 were detected in any intervention arm compared to control, the IGF-1/IGFBP-3 ratio increased significantly in the diet (+5.0%, p<0.01) and diet + exercise (+5.4%, p<0.01) groups compared to control. Greater weight loss was positively associated with change in both IGF-1 (ptrend=0.017) and IGF-1/IGFBP-3 ratio (ptrend<0.001) in the diet group, but inversely with change in IGFBP-3 in the diet + exercise group (ptrend=0.01). No consistent interaction effects with baseline BMI were detected. Modified IGF-1 bioavailability is unlikely to be a mechanism through which caloric restriction reduces cancer risk in postmenopausal women.

Favorable modulation of benign breast tissue and serum risk biomarkers is associated with >10 % weight loss in postmenopausal women

“…An increase in the ratio of IGF-1: IGFBP3 has been previously reported with weight loss [47] and was observed for both <10% and >10 % loss groups (Figure 1; Tables 3 and 3A). …”

Dietary Weight Loss and Exercise Effects on Serum Biomarkers of Angiogenesis in Overweight Postmenopausal Women: A Randomized Controlled Trial

“…(30-32,34,35) Our findings here indicate that exercise alone – either by intervention arm, or when stratified by changes in VO2max – had no effect on PEDF, PAI-1 or VEGF. With the exception of PEDF, weight-loss in the exercise arm was not associated with alterations in levels of these analytes.…”

Adiposity and cancer risk: new mechanistic insights from epidemiology

“…An alterna tive and more plausible explanation is that the lack of substantial change in some intermediary biomarkers (for example, IGF1) in a cancerprotective direction, in the face of substantial weight reduction, argues against that biomarker being a key intermediary in obesity associated carcinogenesis. One recent large randomized trial of dietary and exercise interventions reported no significant changes in IGF1 and IGFBP3, despite sub stantial reductions in body weight in the experimental groups 113 , leading the authors to remark that: "modi fied IGF1 bioavailability is unlikely to be a mechanism through which caloric restriction reduces cancer risk". 114 .…”