Abstract
Aims/hypothesis: We aimed to examine associations of newborn anthropometric measures with childhood glucose metabolism with the hypothesis that greater newborn birthweight, adiposity and cord C-peptide are associated with higher childhood glucose levels and lower insulin sensitivity. Methods: Data from the international, multi-ethnic, population-based Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study were used. The analytic cohort included 4155 children (mean age [SD], 11.4 [1.2] years; 51.0% male). Multiple linear regression was used to examine associations of primary predictors, birthweight, newborn sum of skinfolds (SSF) and cord C-peptide, from HAPO with continuous child glucose outcomes from the HAPO Follow-Up Study. Results: In an initial model that included family history of diabetes and maternal BMI during pregnancy, birthweight and SSF demonstrated a significant, inverse association with 30 min and 1 h plasma glucose levels. In the primary model, which included further adjustment for maternal sum of glucose z scores from an oral glucose tolerance test during pregnancy, the associations were strengthened, and birthweight and SSF were inversely associated with fasting, 30 min, 1 h and 2 h plasma glucose levels. Birthweight and SSF were also associated with higher insulin sensitivity (Matsuda index) (β = 1.388; 95% CI 0.870, 1.906; p < 0.001; β = 0.792; 95% CI 0.340, 1.244; p < 0.001, for birthweight and SSF higher by 1 SD, respectively) in the primary model, while SSF, but not birthweight, was positively associated with the disposition index, a measure of beta cell compensation for insulin resistance (β = 0.034; 95% CI 0.012, 0.056; p = 0.002). Cord C-peptide levels were inversely associated with Matsuda index (β = −0.746; 95% CI −1.188, −0.304; p < 0.001 for cord C-peptide higher by 1 SD) in the primary model. Conclusions/interpretation: This study demonstrates that higher birthweight and SSF are associated with greater childhood insulin sensitivity and lower glucose levels following a glucose load, associations that were further strengthened after adjustment for maternal glucose levels during pregnancy. [Figure not available: see fulltext.]
| Original language | English (US) |
|---|---|
| Pages (from-to) | 561-570 |
| Number of pages | 10 |
| Journal | Diabetologia |
| Volume | 64 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2021 |
Funding
Some of the data were presented as an abstract at the 101st Annual Meeting of the Endocrine Society in 2019. The HAPO Follow-Up Study investigators are grateful to all mothers and children who participated in HAPO and the HAPO Follow-Up Study. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. JLJ and PMC acquired data, interpreted the data and participated in writing the manuscript. MEB, BEM, LPL and WLL conceived and designed the study, researched the literature, interpreted the data and wrote the manuscript. ARD designed the study, acquired data, interpreted the data and wrote the manuscript. AK analysed the data and participated in writing the manuscript. DMS researched the literature, designed the study, acquired data, analysed the data, interpreted the data and wrote the manuscript. All authors reviewed the final version of the manuscript. WLL and DMS are the guarantors of this work and, as such, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The HAPO Follow-Up Study is funded by grant 1U01DK094830 from the National Institute of Diabetes, Digestive, and Kidney Diseases and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The HAPO Study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01-HD-34242 and R01-HD-34243). HAPO Follow-Up Study data were collected and managed using REDCap electronic data capture tools hosted at Northwestern University Feinberg School of Medicine (FSM). REDCap is supported at FSM by the Northwestern University Clinical and Translational Science (NUCATS) Institute. Research reported in this publication was supported, in part, by the National Institutes of Health’s National Center for Advancing Translational Sciences, grants UL1TR001422 and TL1TR001423. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgements Authors’ relationships and activities Contribution statement
Keywords
- Birthweight
- Childhood glucose metabolism
- Childhood plasma glucose
- Fetal exposures
- Newborn adiposity
- Newborn anthropometrics
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
