Circulating IGF-axis protein levels and their relation with levels of plasma adipocytokines and macronutrient consumption in women.

OBJECTIVE: Circulating free insulin-like growth factor (IGF)-I and its binding proteins, most notably, IGFBP-1 and IGFBP-2, have been prospectively associated with incident type 2 diabetes in women. However, little is known regarding the factors that may influence these IGF-axis protein levels. The aim is to study the relation of IGF-axis protein levels with adipcytokines, macronutrient consumption, and other factors related to diabetes. DESIGN: Fasting plasma from 558 controls enrolled in a nested case-control study within the Nurses' Health Study of incident type 2 diabetes in women was tested for: IGF-axis proteins (free and total IGF-I, IGFBP-1, IGFBP-2, IGFBP-3), adipocytokines (leptin, adiponectin, resistin), soluble leptin receptor (sOB-R), inflammatory factors (IL-18 and C-reactive protein (CRP)), insulin, and glycated hemoglobin (HbA1C). RESULTS: In multivariate models, each 1% increase in sOB-R (mean 34.9ng/mL, standard deviation (SD) ±11.3) was associated with -0.20% total IGF-I (P=0.0003) and -0.42% free IGF-I (P=0.002), as well as 0.73% higher IGFBP-1 (P<0.0001) and 0.27% IGFBP-2 (P=0.003). For example, a one SD change from the mean sOB-R level was associated with 11% lower free IGF-I. Insulin levels (mean 6.8μU/mL±5.3) were inversely and adiponectin (mean 18.3μg/mL±7.4) positively associated with IGFBP-1 and IGFBP-2 (all P<0.01). Consumption of dairy protein, monounsaturated fats, and saturated fats, was also correlated with IGF-axis protein levels (all P<0.05). CONCLUSIONS: Several molecular factors and macronutrients were independently associated with plasma IGF-axis protein levels. Which of these, if any, reflect biologic relationships that can be intervened upon to influence IGF-axis protein concentrations warrants further investigation.