Abstract
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
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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.
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Our study also investigates factors affecting plasma insulin in preterm infants along with comorbidities commonly seen during the neonatal intensive care stay.
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Our work reaffirms the importance of Developmental Origins of Health and Disease with regards to in utero programming of insulin levels.
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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.
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Data availability
The datasets generated during and/or analyzed during the current study are not publicly available due to Human Subject Protection requirements but are available from the corresponding author on reasonable request and after IRB review and approval.
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Funding
The Boston Birth Cohort was supported in part by the March of Dimes PERI grants (20-FY02-56, #21-FY07-605); the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number UJ2MC31074, Autism Single Investigator Innovation Program; and the National Institutes of Health (NIH) grants (R21ES011666, 2R01HD041702, R21HD066471, U01AI090727, R21AI079872, R01HD086013, R01HD098232, R21AI154233, R01ES031272, and R01ES031521). M.Z. is supported by the American Heart Association (Award Number: 827990). This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the US government.
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K.M., X.W., and M.Z .conceptualized and designed the study, supervised data collection, performed the statistical analyses, drafted the initial manuscript, and reviewed and revised the manuscript. X.H. and G.W. assisted with the study design, designed the data collection instruments, collected data, and reviewed and revised the manuscript. C.Z. assisted with the study design and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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In this secondary analysis of data, no consent was required. Consent was obtained at initial cohort enrollment.
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Makker, K., Zhang, M., Wang, G. et al. Early-life determinants of childhood plasma insulin levels: implications for primordial prevention of diabetes. Pediatr Res 93, 189–197 (2023). https://doi.org/10.1038/s41390-022-02070-3
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DOI: https://doi.org/10.1038/s41390-022-02070-3
