Context and objectives -As an adverse intrauterine environment is thought to induce insulin resistance, our objective was to investigate the relationships between birth weight, BMI and change in body size over the life course and insulin resistance.

Setting, design and participants – Cross sectional study in a cohort of 1194 female twins aged 18 to 74 years. The relationship between birth weight and insulin resistance was analysed using a regression method allowing for a simultaneous estimation of within and between-pair influences. The approach allows the influence of individual fetal nutrition on adult insulin resistance to be distinguished from effects that are mediated by confounding factors in the maternal environment.

Main outcome measures – Insulin resistance, as measured by the Homeostasis Model Assessment.

Results - Individual level regression analyses showed no significant relationship between birth weight and insulin resistance. There was a significant positive relationship between insulin resistance and current BMI (a 26% increase in insulin resistance per SD increase in BMI, CI: 22.6 to 29.5%). This significant relationship was accounted for in equal part by individual-specific effects and by confounding factors in the shared environment of the twins. The relationship with birth weight became significant only after adjustment for BMI and was mediated only through between pair differences.

Conclusions - These results suggest that insulin resistance is influenced more by current body size than birth weight, and that postnatal growth is potentially more important than fetal growth in the subsequent development of insulin resistance.