Early-life determinants of childhood plasma insulin levels: implications for primordial prevention of diabetes

Background: We earlier reported prematurity as an independent risk factor for elevated insulin levels. Investigation is still lacking on the influence of prenatal and perinatal factors on childhood insulin levels. Methods: In this secondary analysis of a prospective birth cohort, plasma insulin levels were measured at birth and early childhood. Regression models identified early-life factors associated with the primary outcome: log-transformed childhood plasma insulin levels. Results: One thousand one hundred and nine children had insulin levels at birth and 825 at both time points. Compared to term, preterm infants had higher plasma insulin levels (geometric mean) at birth (612, 95% CI 552–679 vs. 372, 95% CI 345–402 pmol/ml) and in early childhood (547, 95% CI 494–605 vs. 445, 95% CI 417–475 pmol/ml). Factors associated with higher early childhood insulin levels included higher insulin level at birth, black race, female sex, maternal smoking during pregnancy, maternal perceived stress, in utero drug exposure, maternal pregestational diabetes mellitus, and maternal preconception overweight and obesity. Conclusions: In this high-risk US birth cohort, we identified multiple prenatal and perinatal risk factors for higher early childhood insulin levels, in addition to prematurity. These findings lend support to primordial preventive strategies for diabetes mellitus. Impact: In this secondary analysis of a large prospective study from a high-risk racially diverse cohort, we identify biological and social factors that contribute to elevated levels of plasma insulin in early childhood.Our study also investigates factors affecting plasma insulin in preterm infants along with comorbidities commonly seen during the neonatal intensive care stay.Our work reaffirms the importance of Developmental Origins of Health and Disease with regards to in utero programming of insulin levels.Our work supports the possibility that primordial preventive strategies for diabetes mellitus in high-risk populations may need to begin as early as the prenatal period.