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.
OBJECTIVE
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
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.
Liu
E H
EH
Diabetes Branch, National Institute of Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Digon
B J
BJ
Hirshberg
B
B
Chang
R
R
Wood
B J
BJ
Neeman
Z
Z
Kam
A
A
Wesley
R A
RA
Polly
S M
SM
Hofmann
R M
RM
Rother
K I
KI
Harlan
D M
DM
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D002908:Chronic Disease; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D005260:Female; D006503:Hepatic Veins; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000637:transplantation*; D016381:Islets of Langerhans Transplantation; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D011169:Portal Vein; D012038:Regeneration / Q000502:physiology; D014184:Transplantation, Homologous
D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D007166:Immunosuppressive Agents; D007328:Insulin