AIMS: This study examined the association of gravida C-peptide with progeny islet function and insulin sensitivity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS). METHODS: Pregnancy 3rd trimester oral glucose tolerance test (OGTT), cord blood, and offspring OGTT glucose, C-peptide and insulin at age 10-14 years were analyzed for 4,121 mother-child dyads. Gravida fasting and 1-hour C-peptide concentration correlations with cord blood and childhood C-peptide, insulin, insulinogenic index and insulin sensitivity, and insulin resistance [HOMA-IR]), were assessed by multiple linear regression. Maternal covariates included age, gestational age, BMI and glucose at OGTT
child covariates included age, sex, pubertal stage, BMI z score and glucose. RESULTS: Gravida fasting and 1-hour OGTT C-peptide was positively correlated with cord blood C-peptide, offspring OGTT C-peptide and insulin concentrations at fasting, 30 min, 1-hour and 2-hour at 10-14 years of age. Maternal fasting and 1-hour C-peptide concentrations were positively correlated with the insulinogenic index and HOMA-IR but inversely correlated with insulin sensitivity. Maternal C-peptide explained more variance than maternal glucose concentrations (3.0-17.9 % vs 0.2-3.5 %). CONCLUSIONS/INTERPRETATION: The correlation between gravida and offspring C-peptide suggests that without crossing the placenta, insulin may influence the offspring pancreatic beta-cell development and insulin sensitivity.