title: Circulating IGF-axis protein levels and their relation with levels of plasma adipocytokines and macronutrient consumption in women.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States. Electronic address: jeannette.beasley@einstein.yu.edu.
authors.forename: Jeannette M
authors.initials: JM
authors.lastname: Beasley
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Wedick
authors.affiliation: US Outcomes Research, US Medical Affairs, Merck & Co., North Wales, PA, United States.
authors.forename: Swapnil N
authors.initials: SN
authors.lastname: Rajpathak
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Holmes
authors.affiliation: Department of Epidemiology Biostatistics, School of Public Health, Imperial College, London, UK.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States.
authors.forename: Judith
authors.initials: J
authors.lastname: Wylie-Rosett
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.affiliation: Department of Medicine and Oncology, Cancer Prevention Research Unit, Lady Davis Research Institute of Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States.
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
mesh_terms: D054392:Adipokines / Q000097:blood*; D016022:Case-Control Studies; D004032:Diet; D004044:Dietary Proteins / Q000378:metabolism; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D016014:Linear Models; D008875:Middle Aged
chemical_list: D054392:Adipokines; D004044:Dietary Proteins; D018969:Insulin-Like Growth Factor Binding Proteins
keywords: Adipocytokines; Free IGF-I; IGF-I; IGFBP-1; IGFBP-2; IGFBP-3; Macronutrients