Life course determinants of insulin secretion and sensitivity at age 50 years: the Newcastle thousand families study

Abstract

Background: Suboptimal nutrition during fetal life and infancy is suggested to increase insulin resistance in adulthood. This study investigated the proportion of variance in insulin secretion and resistance accounted for by factors operating at different stages of life using a cohort of all 1142 births in the city of Newcastle, UK in May and June 1947.

Methods: Detailed information was collected prospectively during childhood, including birth weight, growth and socio-economic circumstances. At age 50, 412 study members attended for clinical examination. Fasting and 30-min plasma insulin and glucose levels were determined and HOMA-IR and insulin secretion derived.

Results: Birth weight was not a significant predictor of HOMA-IR after adjustment for percent body-fat and waist-hip ratio. Duration of breastfeeding was significantly negatively associated with HOMA-IR in men. For both genders, fetal life explained directly little variation in either HOMA-IR or insulin secretion (0.1-5.6%). Compared to early life, adult lifestyle and body composition directly explained larger proportions of the variances for insulin secretion and HOMA-IR for men (11 and 22% respectively) and women (5.9 and 34%).

Conclusions: Insulin secretion is largely unexplained by these data. For insulin resistance, the evidence suggests a limited impact of early life and a larger impact of adult factors.