Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study: newborn anthropometrics and childhood glucose metabolism

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. Graphical abstract.

Keywords: Birthweight; Childhood glucose metabolism; Childhood plasma glucose; Fetal exposures; Newborn adiposity; Newborn anthropometrics.

Fig. 1

Association of birthweight, newborn SSF and cord C-peptide with childhood insulin sensitivity and oDI. The β values (95% CIs) for newborn birthweight (a), SSF (b) and cord C-peptide (c) higher by 1 SD with the Matsuda index are shown, as are associations of birthweight (d), SSF (e) and cord C-peptide (f) higher by 1 SD with oDI. Results are presented for each outcome for model 1 (M01, red) and model 2 (M02, blue)

Fig. 2

Measures of glucose metabolism across SSF thickness quantiles. Quantiles of SSF ranging from <10th percentile to >90th percentile were determined. The mean ± SEM of fasting (a), 30 min (b), 1 h (c) and 2 h (d) glucose as well as the Matsuda index (e) and oDI (f) across the quantiles of SSF were determined