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

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 94-OR
Author(s):  
CLAIRE L. MEEK ◽  
RICHARD A. ORAM ◽  
TIMOTHY J. MCDONALD ◽  
DENICE FEIG ◽  
ANDREW T. HATTERSLEY ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Third Trimester ◽  
C Peptide ◽  
Pancreatic Regeneration ◽  
The Third

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

Diabetes Care ◽  
2021 ◽  
pp. dc210028
Author(s):  
Claire L. Meek ◽  
Richard A. Oram ◽  
Timothy J. McDonald ◽  
Denice S. Feig ◽  
Andrew T. Hattersley ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Third Trimester ◽  
C Peptide ◽  
Pancreatic Regeneration ◽  
The Third

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

2021 ◽  
Author(s):  
Claire L Meek ◽  
Richard A Oram ◽  
Timothy J McDonald ◽  
Denice S Feig ◽  
Andrew T Hattersley ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cord Blood ◽  
Geometric Mean ◽  
Maternal Serum ◽  
Cell Regeneration ◽  
Third Trimester ◽  
C Peptide ◽  
Beta Cell Regeneration

Objective: We assessed longitudinal patterns of maternal C-peptide concentration to examine the hypothesis of beta-cell regeneration in type 1 diabetes pregnancy. <p>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. </p> <p>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. </p> <p>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.</p>

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

2021 ◽  
Author(s):  
Claire L Meek ◽  
Richard A Oram ◽  
Timothy J McDonald ◽  
Denice S Feig ◽  
Andrew T Hattersley ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cord Blood ◽  
Geometric Mean ◽  
Maternal Serum ◽  
Cell Regeneration ◽  
Third Trimester ◽  
C Peptide ◽  
Beta Cell Regeneration

Objective: We assessed longitudinal patterns of maternal C-peptide concentration to examine the hypothesis of beta-cell regeneration in type 1 diabetes pregnancy. <p>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. </p> <p>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. </p> <p>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.</p>

1917-P: Alpha-Cell Function in Patients with Type 1 Diabetes Is Compromised with Different Levels of Residual C-Peptide

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1917-P
Author(s):  
LINGYU ZHANG ◽  
YUWEN SHI ◽  
YITING HUANG ◽  
QIZHEN HU ◽  
YAO QIN ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Cell Function ◽  
Alpha Cell ◽  
C Peptide ◽  
Alpha Cell Function ◽  
Different Levels

scholarly journals One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: an open parallel controlled clinical study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Lu ◽  
Shan-mei Shen ◽  
Qing Ling ◽  
Bin Wang ◽  
Li-rong Li ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Stromal Cells ◽  
Treated Group ◽  
Control Group ◽  
Adult Onset ◽  
Β Cell ◽  
Juvenile Onset ◽  
C Peptide

Abstract Background The preservation or restoration of β cell function in type 1 diabetes (T1D) remains as an attractive and challengeable therapeutic target. Mesenchymal stromal cells (MSCs) are multipotent cells with high capacity of immunoregulation, which emerged as a promising cell-based therapy for many immune disorders. The objective of this study was to examine the efficacy and safety of one repeated transplantation of allogeneic MSCs in individuals with T1D. Methods This was a nonrandomized, open-label, parallel-armed prospective study. MSCs were isolated from umbilical cord (UC) of healthy donors. Fifty-three participants including 33 adult-onset (≥ 18 years) and 20 juvenile-onset T1D were enrolled. Twenty-seven subjects (MSC-treated group) received an initial systemic infusion of allogeneic UC-MSCs, followed by a repeat course at 3 months, whereas the control group (n = 26) only received standard care based on intensive insulin therapy. Data at 1-year follow-up was reported in this study. The primary endpoint was clinical remission defined as a 10% increase from baseline in the level of fasting and/or postprandial C-peptide. The secondary endpoints included side effects, serum levels of HbA1c, changes in fasting and postprandial C-peptide, and daily insulin doses. Results After 1-year follow-up, 40.7% subjects in MSC-treated group achieved the primary endpoint, significantly higher than that in the control arm. Three subjects in MSC-treated group, in contrast to none in control group, achieved insulin independence and maintained insulin free for 3 to 12 months. Among the adult-onset T1D, the percent change of postprandial C-peptide was significantly increased in MSC-treated group than in the control group. However, changes in fasting or postprandial C-peptide were not significantly different between groups among the juvenile-onset T1D. Multivariable logistic regression assay indicated that lower fasting C-peptide and higher dose of UC-MSC correlated with achievement of clinical remission after transplantation. No severe side effects were observed. Conclusion One repeated intravenous dose of allogeneic UC-MSCs is safe in people with recent-onset T1D and may result in better islet β cell preservation during the first year after diagnosis compared to standard treatment alone. Trial registration ChiCTR2100045434. Registered on April 15, 2021—retrospectively registered, http://www.chictr.org.cn/

scholarly journals Insulin’s Discovery: New Insights on Its Hundredth Birthday: From Insulin Action and Clearance to Sweet Networks

2021 ◽  
Vol 22 (3) ◽  
pp. 1030
Author(s):  
Melanie Leroux ◽  
Martial Boutchueng-Djidjou ◽  
Robert Faure
Keyword(s):  
Type 1 Diabetes ◽  
Cell Surface ◽  
20Th Century ◽  
Insulin Action ◽  
100Th Anniversary ◽  
The Body ◽  
Nobel Lecture ◽  
Surface Receptors ◽  
The Third

In 2021, the 100th anniversary of the isolation of insulin and the rescue of a child with type 1 diabetes from death will be marked. In this review, we highlight advances since the ingenious work of the four discoverers, Frederick Grant Banting, John James Rickard Macleod, James Bertram Collip and Charles Herbert Best. Macleoad closed his Nobel Lecture speech by raising the question of the mechanism of insulin action in the body. This challenge attracted many investigators, and the question remained unanswered until the third part of the 20th century. We summarize what has been learned, from the discovery of cell surface receptors, insulin action, and clearance, to network and precision medicine.

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