Anzeige
Erschienen in:
01.02.2011 | Article
Beta cell function during rapamycin monotherapy in long-term type 1 diabetes
Erschienen in: Diabetologia | Ausgabe 2/2011
Einloggen, um Zugang zu erhaltenAbstract
Aims/hypothesis
Type 1 diabetes is considered non-reversible at end-stage disease when there is no measurable insulin production. However, there are indications that insulin-producing beta cells could be present or return if autoimmunity could be controlled. We therefore sought to determine whether immunosuppression therapy can reinstate beta cell function in patients with long-term type 1 diabetes.
Methods
We examined pancreatic beta cell function in 22 patients with long-term type 1 diabetes (median disease duration 27 years), who had been receiving rapamycin monotherapy (0.1 mg/kg; target trough levels 8–10 ng/ml; 26–314 days) as pre-conditioning for islet transplantation. As control, beta cell function was measured in 14 patients (median disease duration 17 years) who were waiting for an islet transplant without rapamycin pre-conditioning.
Results
Fasting C-peptide increased from <0.03 nmol/l (0.0066 nmol/l, interquartile range [IQR] 0.0003–0.023) at baseline to 0.039 nmol/l (IQR 0.0066–0.096) at end of rapamycin monotherapy (p < 0.005). In 12 patients, fasting C-peptide increased to >0.076 nmol/l (C-peptide responders). Exogenous insulin requirement decreased from 0.64 U/kg daily (IQR 0.56–0.72) to 0.57 U/kg (IQR 0.45–0.70; p = 0.01), but this reduction was significant only in the 12C-peptide-responsive patients. Rapamycin monotherapy was also associated with a decrease in insulin antibody titre (median decrease 110 to 35.9 U/ml; p < 0.001) and fasting serum proinsulin (median decrease 0.51 to 0.28 pmol/l; p = 0.001). All variables remained unchanged in the 14 control patients.
Conclusions/interpretation
Therapies to reinstate beta cell function may be applicable to patients with long-term C-peptide-negative type 1 diabetes.
Trial registration
ClinicalTrial.gov NCT01060605
Funding
This study was funded by Telethon Italy and the Juvenile Diabetes Research Foundation (JT01Y01 and grant no. 6-2006-1098) and the European Union (DIAPREPP Project, FP7-HEALTH-202013). E. Bonifacio is funded by the Deutsche Forschungsgemeinschaft (FZ111).