Reappearance of C-Peptide During the Third Trimester of Pregnancy in Type 1 Diabetes: Pancreatic Regeneration or Fetal Hyperinsulinism?

OBJECTIVE We assessed longitudinal patterns of maternal C-peptide concentration to examine the hypothesis of beta-cell regeneration in pregnancy with type 1 diabetes. RESEARCH DESIGN AND METHODS C-peptide was measured on maternal serum samples from 127 participants (12, 24, and 34 weeks) and cord blood during the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT). C-peptide was measured using a highly sensitive direct and solid-phase competitive electrochemiluminescent immunoassay. RESULTS Three discrete patterns of maternal C-peptide trajectory were identified: pattern 1, undetectable throughout pregnancy, n = 74 (58%; maternal C-peptide <3 pmol/L); pattern 2, detectable at baseline, n = 22 (17%; maternal C-peptide 7-272 pmol/L at baseline); and pattern 3, undetectable maternal C-peptide at 12 and 24 weeks, which first became detectable at 34 weeks, n = 31 (24%; maternal C-peptide 4-26 pmol/L at 34 weeks). Baseline characteristics and third trimester glucose profiles of women with pattern 1 and pattern 3 C-peptide trajectories were similar, but women in pattern 3 had suboptimal glycemia (50% time above range) at 24 weeks' gestation. Offspring of women with pattern 3 C-peptide trajectories had elevated cord blood C-peptide (geometric mean 1,319 vs. 718 pmol/L; P = 0.007), increased rates of large for gestational age (90% vs. 60%; P = 0.002), neonatal hypoglycemia (42% vs. 14%; P = 0.001), and neonatal intensive care admission (45% vs. 23%; P = 0.023) compared with pattern 1 offspring. CONCLUSIONS First maternal C-peptide appearance at 34 weeks was associated with midtrimester hyperglycemia, elevated cord blood C-peptide, and high rates of neonatal complications. This suggests transfer of C-peptide from fetal to maternal serum and is inconsistent with pregnancy-related beta-cell regeneration.