Birth weight modifies the relation between adulthood levels of insulin-like growth factor-1 and type 2 diabetes: a prospective cohort study

INTRODUCTION: Insulin-like growth factor-1 (IGF-1) has been implicated in fetal and early-life growth and development of type 2 diabetes (T2D). We aimed to examine the interaction between circulating IGF-1 and birth weight in relation to risk of T2D. RESEARCH DESIGN AND METHODS: We included 181 090 adults, aged 39–70 years in the UK Biobank Study, who were free of diabetes or major cardiovascular diseases at baseline. Serum IGF-1 levels were determined using chemiluminescent immunoassay method. Birth weight was self-reported; a Genetic Risk Score (GRS) was calculated to define the genetically determined birth weight. The outcome was the incidence of T2D. RESULTS: We identified 3299 incident T2D cases over an average of 9.9 years of follow-up. Among the participants with birth weight of ≥2.5 kg, IGF-1 levels were inversely associated with T2D risk in a dose-dependent manner (p-trend<0.001). In contrast, the association was not significant among those with birth weight of <2.5 kg (p-interaction=0.001). The GRS of birth weight did not interact with IGF-1 levels on T2D risk. CONCLUSIONS: Our results indicate that birth weight significantly modifies the relation between adulthood levels of circulating IGF-1 and the risk of T2D. Our findings highlight the importance of early-life risk factors in the development of the lifecourse prevention strategies targeting IGF-1 and T2D.