Jeannette M Beasley1, Nicole M Wedick2, Swapnil N Rajpathak3, Xiaonan Xue4, Michelle D Holmes5, Marc J Gunter6, Judith Wylie-Rosett4, Thomas E Rohan4, Michael Pollak7, Robert C Kaplan4, Frank B Hu5, Qi Sun8, Howard D Strickler4. 1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States. Electronic address: jeannette.beasley@einstein.yu.edu. 2. Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States. 3. US Outcomes Research, US Medical Affairs, Merck & Co., North Wales, PA, United States. 4. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States. 5. 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. 6. Department of Epidemiology Biostatistics, School of Public Health, Imperial College, London, UK. 7. Department of Medicine and Oncology, Cancer Prevention Research Unit, Lady Davis Research Institute of Jewish General Hospital, McGill University, Montreal, Quebec, Canada. 8. Department of Epidemiology, Harvard School of Public Health, Boston, MA, United States.
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. 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.
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.
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