Abstract
Aims/hypothesis: We measured serum C-peptide (at least 0.167 nmol/l) in 54 of 141 (38%) patients with chronic type 1 diabetes and sought factors that might differentiate those with detectable C-peptide from those without it. Finding no differences, and in view of the persistent anti-beta cell autoimmunity in such patients, we speculated that the immunosuppression (to weaken autoimmune attack) and euglycaemia accompanying transplant-based treatments of type 1 diabetes might promote recovery of native pancreatic beta cell function. Methods: We performed arginine stimulation tests in three islet transplant and four whole-pancreas transplant recipients, and measured stimulated C-peptide in select venous sampling sites. On the basis of each sampling site's C-peptide concentration and kinetics, we differentiated insulin secreted from the individual's native pancreatic beta cells and that secreted from allografted beta cells. Results: Selective venous sampling demonstrated that despite long-standing type 1 diabetes, all seven beta cell allograft recipients displayed evidence that their native pancreas secreted C-peptide. Yet even if chronic immunosuppression coupled with near normal glycaemia did improve native pancreatic C-peptide production, the magnitude of the effect was quite small. Conclusions/interpretation: Some native pancreatic beta cell function persists even years after disease onset in most type 1 diabetic patients. However, if prolonged euglycaemia plus anti-rejection immunosuppressive therapy improves native pancreatic insulin production, the effect in our participants was small. We may have underestimated pancreatic regenerative capacity by studying only a limited number of participants or by creating conditions (e.g. high circulating insulin concentrations or immunosuppressive agents toxic to beta cells) that impair beta cell function. Trial registration: ClinicalTrials.gov NCT00246844 and NCT00006505.
Original language | English (US) |
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Pages (from-to) | 1369-1380 |
Number of pages | 12 |
Journal | Diabetologia |
Volume | 52 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2009 |
Externally published | Yes |
Keywords
- Beta cell regeneration
- C-peptide
- Islet transplantation
- Pancreas transplantation
- Type 1 diabetes
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism