Claire L Meek1,2,3, Richard A Oram4, Timothy J McDonald4,5, Denice S Feig6,7, Andrew T Hattersley4, Helen R Murphy. 1. The Wellcome-MRC Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge, U.K. clm70@cam.ac.uk. 2. Wolfson Diabetes and Endocrinology Clinic, Cambridge University Hospitals, Addenbrooke's Hospital, Cambridge, U.K. 3. Department of Clinical Biochemistry, Cambridge University Hospitals, Addenbrooke's Hospital, Cambridge, U.K. 4. Department of Diabetes Research, University of Exeter, Royal Devon and Exeter Hospital, Exeter, U.K. 5. Academic Department of Blood Sciences, Royal Devon and Exeter NHS Foundation Trust, Exeter, U.K. 6. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Department of Medicine, University of Toronto, Ontario, Canada. 7. Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada.
Abstract
OBJECTIVE: We assessed longitudinal patterns of maternal C-peptide concentration to examine the hypothesis of β-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 β-cell regeneration.
OBJECTIVE: We assessed longitudinal patterns of maternal C-peptide concentration to examine the hypothesis of β-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 β-cell regeneration.
Authors: Ernesto Maddaloni; Geremia B Bolli; Brian M Frier; Randie R Little; Richard D Leslie; Paolo Pozzilli; Raffaela Buzzetti Journal: Diabetes Obes Metab Date: 2022-06-28 Impact factor: 6.408