Content: Intrauterine exposure to maternal diabetes and large size at birth are known risk factors for the subsequent development of insulin resistance and metabolic syndrome (MSX). Although Hispanic youth have been shown to have a high prevalence of MSX, it is unknown whether metabolic abnormalities and a predisposition for glucose intolerance are present at birth.

Objective: To determine if abnormalities in insulin sensitivity (S_I) exist at or soon after birth in large for gestational age (LGA) neonates born to Hispanic women with and without gestational diabetes.

Design/Patients/Setting: Forty-two term Hispanic neonates were enrolled for cross-sectional studies at 24-48h after birth and included: 9 LGA neonates delivered of women with gestational diabetes (LGA-IDM), 12 LGA but not IDM neonates, 11 poorly grown (at 5-10^th%) and 10 appropriate for gestational age (AGA) neonates. Insulin sensitivity and secretion were measured by shortened fasting intravenous glucose tolerance test.

Main Outcome Measure: Insulin Sensitivity Index (S_I) within 48h of birth.

Results: Neonates were studied at 36±11h postnatal, and all groups were euglycemic at the time of study. However, the S_I was significantly lower (P<0.05, ANOVA) in LGA-IDM (3.0±0.7[SEM] mU/L·min) and LGA-nonIDM (2.2±0.4 mU/L·min) cohorts in comparison to poorly grown (5.0±0.7 mU/L·min) and AGA controls (5.4±0.8 mU/L·min). Insulin secretion did not differ between groups.

Conclusions: Reduced S_I is present soon after birth in Hispanic LGA neonates born to mothers with and without gestational diabetes, demonstrating the onset of insulin resistance before birth and evidence of altered fetal programming.