Aims/hypothesis: An increased risk of type 2 diabetes mellitus is associated with low birthweight after full-term gestation, including amplification of this risk by weight gain during infancy and adult body composition. Premature birth is also associated with insulin resistance, but studies conducted so far have not provided follow-up into adulthood. We studied the effects of (1) lower birthweight (as standard deviation score [SDS]) and infancy weight gain on insulin resistance in 19-year-olds born before 32 weeks of gestation, and (2) the interaction between lower birthweight SDS and infancy weight gain, as well as between lower birthweight and adult body composition, on insulin resistance. Methods: This was a prospective follow-up study in 346 subjects from the Project on Preterm and Small-for-gestational-age infants cohort, in whom fasting glucose, insulin and C-peptide levels were measured at 19 years. Insulin resistance was calculated with homeostatic modelling (homeostatic model assessment for insulin resistance index [HOMA-IR]). Results: Birthweight SDS was unrelated to the outcomes. Rapid infancy weight gain until 3 months post-term was weakly associated with higher insulin level (p=0.05). Adult fatness was positively associated with insulin and C-peptide levels and HOMA-IR (all p<0.001). On these parameters, there was a statistical interaction between birthweight SDS and adult fat mass (p=0.002 to 0.03). Conclusions/interpretation: In subjects born very preterm, rapid infancy weight gain until 3 months predicted higher insulin levels at 19 years, but the association was weak. Adult obesity strongly predicted higher insulin and C-peptide levels as well as HOMA-IR. The effect of adult fat mass on these parameters was dependent on its interaction with birthweight SDS. © Springer-Verlag 2006.