CONCEPTT_CPeptide_Supp_Mat_R1_2021_03_27_CLEAN_for_resub.pdf (321.75 kB)

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

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posted on 16.06.2021, 22:03 by Claire L Meek, Richard A Oram, Timothy J McDonald, Denice S Feig, Andrew T Hattersley, Helen R Murphy, the CONCEPTT collaborative group
Objective: We assessed longitudinal patterns of maternal C-peptide concentration to examine the hypothesis of beta-cell regeneration in type 1 diabetes pregnancy.

Research Design & Methods: C-peptide was measured on maternal serum samples from 127 participants (12, 24, 34 weeks) and cord blood during the continuous glucose monitoring in type 1 diabetes 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); 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 1319 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 to pattern 1 offspring.

Conclusion: First maternal C-peptide appearance at 34 weeks was associated with mid-trimester 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.


The trial is funded by Juvenile Diabetes Research Foundation (JDRF) grants #17‐2011‐533, and grants under the JDRF Canadian Clinical Trial Network, a public‐private partnership including JDRF and FedDev Ontario and supported by JDRF #80‐2010‐585. Medtronic supplied the CGM sensors and CGM systems at reduced cost. The study sponsor/funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the report; and did not impose any restrictions regarding the publication of the report. CLM is supported by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (DUK-HKF 17/0005712) and the European Foundation for the Study of Diabetes – Novo Nordisk Foundation Future Leaders’ Award (NNF19SA058974). RAO is supported by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (DUK-HKF 16/0005529). TMcD is funded by an NIHR Senior Lecturer Fellowship. ATH is a Wellcome Trust Senior Research fellow. HRM conducts independent research supported by the National Institute for Health Research (Career Development Fellowship, CDF-2013-06-035), and is supported by Tommy’s charity.