Associations of Adiposity from Childhood into Adulthood with Insulin Resistance and the Insulin-Like Growth Factor System: 65-Year Follow-Up of the Boyd Orr Cohort

Abstract

Abstract Context: One metabolic pathway through which adiposity influences disease risk may be via alterations in insulin and IGF metabolism. Objective: Our objective was to investigate associations of adiposity at different stages of life with insulin and the IGF system. Design, Setting, and Participants: The study was a 65-yr follow-up of 728 Boyd Orr cohort participants (mean age, 71 yr) originally surveyed between 1937 and 1939. Main Outcomes: Outcomes included homeostasis model assessment of insulin resistance, total IGF-I and IGF-II, IGF binding protein (IGFBP)-2, and IGFBP-3 in adulthood. Results: Childhood body mass index (BMI) was weakly inversely related to adult IGF-I (coefficient per BMI sd, −3.4 ng/ml; 95% confidence interval, −7.3 to 0.5; P = 0.09). IGF-II (but not IGF-I) increased with higher current fat mass index (coefficient, 26.1 ng/ml; 95% confidence interval, 4.6 to 47.6; P = 0.02) and waist-hip ratio (30.0 ng/ml; 9.4 to 50.5; P = 0.004). IGFBP-2 decreased by 21.2% (17.2 to 24.9; P < 0.001), and homeostasis model assessment of insulin resistance increased by 38.8% (28.9 to 49.6; P < 0.001) per sd higher adult BMI. Among thin adults (BMI tertiles 1 and 2), IGFBP-2 was positively, and insulin resistance was inversely, associated with childhood BMI. Conclusion: There was only weak evidence that associations of childhood BMI with chronic disease risk may be mediated by adult IGF-I levels. Circulating IGFBP-2 in adulthood, a marker for insulin sensitivity, was inversely associated with current adiposity, but overweight children who became relatively lean adults were more insulin sensitive than thinner children. The findings may indicate programming of later insulin sensitivity and consequently IGFBP-2 levels in response to childhood adiposity. The role of IGF-II in obesity-related chronic diseases warrants additional investigation.