Relation of birth weight, body mass index, and change in size from birth to adulthood to insulin resistance in a female twin cohort

Context and Objectives: Because 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: We conducted a cross-sectional study in a cohort of 1194 female twins aged 18-74 yr. The relationship between birth weight and insulin resistance was analyzed 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 was 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 body mass index (BMI) (a 26% increase in insulin resistance per SD increase in BMI; confidence interval, 22.6-29.5%). This significant relationship was accounted for in equal parts 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.