Association of Pregnancy and Childhood C-Peptide Levels-Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO-FUS)

Physiological insulin resistance partitions glucose for the growing fetus during the 2nd and 3rd trimester of pregnancy. The HAPO study has demonstrated that pregnancy hyperglycemia is associated with offspring adiposity, hyperglycemia, and glucose intolerance. Maternal insulin is a key regulator of the glucose physiology but does not cross the placenta. The goal of this study was to identify the association of pregnancy and offspring c-peptide levels, measured during oral glucose tolerance test (OGTT). Method: Using HAPO-FUS data from the NIH-NIDDK repository, multiple linear regression assessed the association of scaled pregnancy fasting and 1-hour c-peptide with cord c-peptide (at birth), and child c-peptide from OGTT at the follow-up visit (ages 10-14 years). Maternal covariates include pregnancy gestational age, BMI, glucose level and field center. Child covariates include age, sex, tanner stage, BMI z-score and glucose level. Multiple imputation was performed using missing at random assumption. Results: A total of 4,802 mother-child pairs were included. Pregnancy c-peptide was associated with cord c-peptide (fasting 0.02 [0.01-0.03], p <.001, 1-hour 0.01 [0.002-0.02], p =.006). Pregnancy fasting c-peptide was also associated with child OGTT c-peptide (fasting 0.03 [0.02-0.04], p <.001; 1-hour 0.11 [0.08-0.15], p <.001; 2-hour 0.01 [0.007-0.02], p <.001) and pregnancy 1-hour c-peptide (fasting 0.01 [0.007-0.02], p <.001; 1-hour 0.15 [0.12-0.17], p <.001; 2-hour 0.11 [0.09-0.14], p <.001). Similar associations were observed with child insulin levels. Pregnancy c-peptide levels were positively associated with HOMA-IR and negatively with child insulin sensitivity and Matsuda index while adjusting for child BMI z-score and pubertal stage. Conclusion: Pregnancy insulin levels are strongly associated with the child insulin response during OGTT. This suggests a role in the offspring pancreas developmental programming. Disclosure H. Zheng: None. A. Rajamoorthi: None. A. Skowronski: None. R. Salem: Other Relationship; Travere Inc. C. A. Leduc: None. V. V. Thaker: None. Funding National Institutes of Health (K23DK110539)