SAT-124 Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study (HAPO FUS): Newborn Anthropometrics and Childhood Glucose Metabolism

The prevalence of insulin resistance and type 2 diabetes (T2DM) in children is increasing, and identifying where prevention can best be implemented is an emerging area of research. The association of low birth weight with long-term risk for poor metabolic health is well established, but the association of newborn size at birth, including adiposity, with measures of glucose metabolism in children has not been fully elucidated. To address this, we used longitudinal data from the international, multi-ethnic Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and HAPO Follow Up Study (FUS). Newborn birth weight (BW) and sum of skinfolds (SSF), as a measure of adiposity, collected during HAPO, together with glucose and C-peptide levels collected during an oral glucose tolerance test (OGTT) in 4160 HAPO FUS offspring at age 10-14 years were examined. Multiple logistic and linear regression were used for statistical analyses to examine associations between primary predictors, BW and SSF, with child metabolic outcomes. Covariate adjustments included HAPO field center, child age, sex, Tanner stage, maternal variables at pregnancy OGTT (age, height, mean arterial pressure, parity (0, 1+), smoking (yes/no), drinking alcohol (yes/no), gestational age), child’s family history of diabetes in first degree relatives and child’s BMI z-score. BW was inversely associated with the 30-min, 1-h, and 2-h plasma glucose levels (Beta=-1.59, CI: -2.53 - -0.65, p<0.0001, Beta=-2.09, CI: -3.30 - -0.88, p=0.007, and Beta=-1.47, CI: -2.28- -0.65, p=0.0004, respectively for BW higher by 1 standard deviation), as was SSF (Beta= -1.40, CI: -2.19 - -0.60, p< 0.0001, Beta=-1.97, CI: -3.00 - -0.94, p=0.0002, and Beta=-0.98, CI: -1.67 - -0.28, p=0.01 respectively for SSF higher by 1 standard deviation). BW and SSF were also associated with a higher Matsuda index, a measure of insulin sensitivity (Beta=1.77, CI: 1.32-2.21, p<0.0001 and Beta=0.89, CI: 0.50-1.27 p<0.0001, respectively). However, only SSF had a positive association with the disposition index, a measure of beta cell compensation for insulin resistance (Beta=0.03, CI: 0.01-0.05, p=0.01). No association was found between BW and SSF and impaired glucose tolerance, while a modest decrease in risk for impaired fasting glucose was seen with higher BW and SSF (OR=-0.83, CI: 0.70-0.98, p=0.03 and OR=0.85, CI: 0.74-0.97, p=0.02, respectively). This study demonstrates that higher BW and newborn adiposity are associated with lower glucose levels and higher insulin sensitivity in childhood. This suggests a complex relationship between birth size and long-term metabolic health in which, after adjusting for child BMI, higher BW and adiposity are associated with better metabolic health during childhood.