Pancreatic beta cell function persists in many patients with chronic type 1 diabetes, but is not dramatically improved by prolonged immunosuppression and euglycaemia from a beta cell allograft

Diabetologia. 2009 Jul;52(7):1369-80. doi: 10.1007/s00125-009-1342-7. Epub 2009 May 6.


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: NCT00006505 NCT00246844.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • C-Peptide / blood
  • C-Peptide / metabolism
  • Chronic Disease
  • Diabetes Mellitus, Type 1* / immunology
  • Diabetes Mellitus, Type 1* / metabolism
  • Diabetes Mellitus, Type 1* / surgery
  • Female
  • Hepatic Veins
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / transplantation*
  • Islets of Langerhans Transplantation*
  • Kidney Transplantation
  • Male
  • Middle Aged
  • Pancreas Transplantation
  • Portal Vein
  • Regeneration / physiology
  • Transplantation, Homologous


  • Biomarkers
  • Blood Glucose
  • C-Peptide
  • Immunosuppressive Agents
  • Insulin

Associated data