scholarly journals GABA induces a hormonal counter-regulatory response in subjects with long-standing type 1 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002442
Author(s):  
Daniel Espes ◽  
Hanna Liljebäck ◽  
Henrik Hill ◽  
Andris Elksnis ◽  
José Caballero-Corbalan ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Controlled Release ◽  
Beta Cell ◽  
Dose Escalation ◽  
Cell Regeneration ◽  
Release Formulation ◽  
Regulatory Response ◽  
Beta Cell Regeneration ◽  
Controlled Release Formulation

IntroductionExperimentally, gamma-aminobutyric acid (GABA) has been found to exert immune-modulatory effects and induce beta-cell regeneration, which make it a highly interesting substance candidate for the treatment of type 1 diabetes (T1D). In many countries, including those in the European Union, GABA is considered a pharmaceutical drug. We have therefore conducted a safety and dose escalation trial with the first controlled-release formulation of GABA, Remygen (Diamyd Medical).Research design and methodsSix adult male subjects with long-standing T1D (age 24.8±1.5 years, disease duration 14.7±2.2 years) were enrolled in an 11-day dose escalation trial with a controlled-release formulation of GABA, Remygen. Pharmacokinetics, glucose control and hormonal counter-regulatory response during hypoglycemic clamps were evaluated at every dose increase (200 mg, 600 mg and 1200 mg).ResultsDuring the trial there were no serious and only a few, transient, adverse events reported. Without treatment, the counter-regulatory hormone response to hypoglycemia was severely blunted. Intake of 600 mg GABA more than doubled the glucagon, epinephrine, growth hormone and cortisol responses to hypoglycemia.ConclusionsWe find that the GABA treatment was well tolerated and established a counter-regulatory response to hypoglycemia in long-standing T1D. Further studies regarding not only the clinical potential of Remygen for beta-cell regeneration but also its potential use as hypoglycemic prophylaxis are warranted.Trail registration numberNCT03635437 and EudraCT2018-001115-73.

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 Direct evidence of attempted beta cell regeneration in an 89-year-old patient with recent-onset type 1 diabetes

Diabetologia ◽  
2006 ◽  
Vol 49 (8) ◽  
pp. 1838-1844 ◽  
Author(s):  
J. J. Meier ◽  
J. C. Lin ◽  
A. E. Butler ◽  
R. Galasso ◽  
D. S. Martinez ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Direct Evidence ◽  
Cell Regeneration ◽  
Beta Cell Regeneration ◽  
Recent Onset ◽  
Onset Type

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 Restrain of beta-cell destruction and stimulation of beta-cell regeneration in type 1 diabetes

2015 ◽  
Vol 14 (3) ◽  
pp. 35-40
Author(s):  
Leszek Szewczyk ◽  
◽  
Anna Bury ◽  
Robert Piekarski ◽  
◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Cell Regeneration ◽  
Beta Cell Regeneration ◽  
Beta Cell Destruction ◽  
Cell Destruction ◽  
Stimulation Of
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