Ane S Kværner1,2,3,4, Dong Hang3,4,5, Edward L Giovannucci3,4,6, Walter C Willett3,4,6, Andrew T Chan6,7, Mingyang Song3,4,7. 1. Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. 2. Norwegian National Advisory Unit on Disease-Related Malnutrition, Oslo University Hospital, Oslo, Norway. 3. Departments of Nutrition and Harvard TH Chan School of Public Health, Boston, MA. 4. Departments of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA. 5. Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention, and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China. 6. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 7. Clinical and Translational Epidemiology Unit and Division of Gastroenterology Massachusetts General Hospital and Harvard Medical School, Boston, MA.
Abstract
Background: A major pathway through which obesity increases the risk of cardiometabolic diseases and cancer is by inducing hormonal and metabolic abnormalities, including hyperinsulinemia and altered insulin-like growth factor (IGF) signaling. However, little is known about the influence of lifetime adiposity on the relevant biomarkers. Objective: The aim of this study was to examine associations of trajectories of body fatness with plasma biomarker concentrations of the insulin-IGF system in 2 large prospective cohorts of US men and women. Design: Associations between trajectories of body fatness and concentrations of plasma C-peptide, IGF-I, IGF-binding protein (IGFBP) 1, IGFBP-3, and the IGF-I-to-IGFBP-3 molar ratio was examined in 9386 women of the Nurses' Health Study and 3941 men of the Health Professionals Follow-Up Study. Group-based trajectory modeling was used to create trajectory groups on the basis of self-reported somatotype data at ages 5, 10, 20, 30, and 40 y and body mass index (BMI) at ages 45, 50, 55, and 60 y. We used multivariate linear regression models to examine the associations of trajectories with biomarker concentrations. Results: Five trajectories of body fatness were identified: "lean-stable," "lean-moderate increase," "lean-marked increase," "medium-stable/increase," and "medium-marked increase." Compared with the lean-stable group, the lean-marked increase and medium-marked increase groups had significantly higher concentrations of C-peptide (percentage difference-women: 44% and 73%; men: 27% and 51%) and lower concentrations of IGFBP-1 (women: -61% and -78%; men: -47% and -65%). Adjustment for current BMI attenuated the association to null for the medium-marked increase group, but the lean-marked increase group still had modestly higher concentrations of C-peptide (women: 10%; men: 6%) and lower concentrations of IGFBP-1 (women: -18%; men: -21%) than the lean-stable group. Conclusions: Adiposity across the life span was associated with higher C-peptide and lower IGFBP-1 concentrations in adulthood. The associations were largely driven by attained adiposity and, to a lesser extent, weight gain in early-middle adulthood. This trial was registered at www.clinicaltrials.gov as NCT03419455.
Background: A major pathway through which obesity increases the risk of cardiometabolic diseases and cancer is by inducing hormonal and metabolic abnormalities, including hyperinsulinemia and altered insulin-like growth factor (IGF) signaling. However, little is known about the influence of lifetime adiposity on the relevant biomarkers. Objective: The aim of this study was to examine associations of trajectories of body fatness with plasma biomarker concentrations of the insulin-IGF system in 2 large prospective cohorts of US men and women. Design: Associations between trajectories of body fatness and concentrations of plasma C-peptide, IGF-I, IGF-binding protein (IGFBP) 1, IGFBP-3, and the IGF-I-to-IGFBP-3 molar ratio was examined in 9386 women of the Nurses' Health Study and 3941 men of the Health Professionals Follow-Up Study. Group-based trajectory modeling was used to create trajectory groups on the basis of self-reported somatotype data at ages 5, 10, 20, 30, and 40 y and body mass index (BMI) at ages 45, 50, 55, and 60 y. We used multivariate linear regression models to examine the associations of trajectories with biomarker concentrations. Results: Five trajectories of body fatness were identified: "lean-stable," "lean-moderate increase," "lean-marked increase," "medium-stable/increase," and "medium-marked increase." Compared with the lean-stable group, the lean-marked increase and medium-marked increase groups had significantly higher concentrations of C-peptide (percentage difference-women: 44% and 73%; men: 27% and 51%) and lower concentrations of IGFBP-1 (women: -61% and -78%; men: -47% and -65%). Adjustment for current BMI attenuated the association to null for the medium-marked increase group, but the lean-marked increase group still had modestly higher concentrations of C-peptide (women: 10%; men: 6%) and lower concentrations of IGFBP-1 (women: -18%; men: -21%) than the lean-stable group. Conclusions: Adiposity across the life span was associated with higher C-peptide and lower IGFBP-1 concentrations in adulthood. The associations were largely driven by attained adiposity and, to a lesser extent, weight gain in early-middle adulthood. This trial was registered at www.clinicaltrials.gov as NCT03419455.
Authors: Qiao-Li Wang; Mingyang Song; Steven K Clinton; Lorelei A Mucci; Jesper Lagergren; Edward L Giovannucci Journal: Eur J Epidemiol Date: 2022-01-13 Impact factor: 8.082
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Authors: Yi Yang; Pierre-Antoine Dugué; Brigid M Lynch; Allison M Hodge; Amalia Karahalios; Robert J MacInnis; Roger L Milne; Graham G Giles; Dallas R English Journal: BMJ Open Date: 2019-08-10 Impact factor: 2.692
Authors: Dong Hang; Xiaosheng He; Ane Sørlie Kværner; Andrew T Chan; Kana Wu; Shuji Ogino; Zhibin Hu; Hongbing Shen; Michael N Pollak; Edward L Giovannucci; Mingyang Song Journal: JNCI Cancer Spectr Date: 2019-08-01