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Diabetologia. 2011 Feb;54(2):433-9. doi: 10.1007/s00125-010-1959-6. Epub 2010 Nov 3.

Beta cell function during rapamycin monotherapy in long-term type 1 diabetes.

Author information

1
Diabetes Research Institute (HSR-DRI), San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy. piemonti.lorenzo@hsr.it

Abstract

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.

PMID:
21046356
DOI:
10.1007/s00125-010-1959-6
[Indexed for MEDLINE]
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