Abstract
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. 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. 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. 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. graphical abstract.> 0.001> 0.001,> 0.001;>