Context: One metabolic pathway through which adiposity influences disease risk may be via alterations in insulin and insulin-like growth factor (IGF) metabolism.

Objective: To investigate associations of adiposity at different stages of the life-course with insulin and the IGF system.

Design, setting, participants: 65-year follow-up of 728 Boyd Orr cohort participants (mean age 71 yr) originally surveyed between 1937-1939.

Main outcomes: Homeostasis model assessment (HOMA) of insulin resistance, total IGF-I and IGF-II, IGF binding protein (BP)-2 and IGFBP-3 in adulthood.

Results: Childhood BMI was weakly inversely related to adult IGF-I (coefficient per BMI SD (SD): -3.4 ng/ml; 95% CI: -7.3, 0.5; P = 0.09). IGF-II (but not IGF-I) increased with higher current fat mass index (coefficient: 26.1 ng/ml; 95% CI: 4.6, 47.6, P = 0.02) and waist-hip ratio (30.0 ng/ml; 9.4, 50.5; P = 0.004). IGFBP-2 decreased by 21.2% (17.2, 24.9; P < 0.001), and HOMA insulin resistance increased by 38.8% (28.9, 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 programing 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 further investigation.