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

Abstract

Aims: Endogenous insulin secretion may increase in type 1 diabetes pregnancy. We assessed longitudinal patterns of maternal C-peptide concentration to investigate potential mechanisms.Methods: Highly-sensitive direct and solid-phase competitive electrochemiluminescent immunoassays measured C-peptide in maternal serum (12, 24, 34 wks; n127) and cord blood (n85) from the continuous glucose monitoring in type 1 diabetes pregnancy trial (CONCEPTT).Results: Three discrete patterns of maternal C-peptide trajectory were identified (Figure1): Pattern 1 undetectable throughout pregnancy (Figure1a; n74; 58%); Pattern 2 detectable at baseline (Figure1b; n22; 17%); Pattern 3 undetectable C-peptide (12 and 24wks), became detectable at 34 wks (Figure1b; n31; 24%). Offspring of women in pattern 3 had higher rates of neonatal hypoglycemia (42% vs. 14%; p=0.001), large-for-gestational-age (Figure1c; 90% vs. 60%; p=0.002) and elevated cord blood C-peptide (Figure 1d; geometric mean 1319 vs. 718 pmol/l; p=0.007) compared to offspring from women in pattern 1, despite comparable 34-week glycemia.Conclusion: Increased C-peptide in maternal serum at 34 weeks suggests fetal hyperinsulinism with fetal-to-maternal transfer not improved maternal beta cell function. First appearance of C peptide in late pregnancy could identify pregnancies at highest risk of neonatal complications.View largeDownload slideView largeDownload slide DisclosureC. L. Meek: None. R. A. Oram: Consultant; Self; Janssen Research & Development, LLC. T. J. Mcdonald: None. D. Feig: Advisory Panel; Self; Novo Nordisk. A. T. Hattersley: None. H. R. Murphy: None.FundingJDRF (17/2011/533, 80/2010/585); Medtronic; Diabetes UK (17/0005712, 16/0005529); European Foundation for the Study of Diabetes; Novo Nordisk Foundation (NNF19SA058974); National Institute for Health Research (CDF-2013-06-035); UK Wellcome Trust; Tommy’s