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.
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.
Authors: A Pugliese; D Brown; D Garza; D Murchison; M Zeller; M J Redondo; M Redondo; J Diez; G S Eisenbarth; D D Patel; C Ricordi Journal: J Clin Invest Date: 2001-03 Impact factor: 14.808
Authors: C Jaeger; J Allendörfer; E Hatziagelaki; T Dyrberg; K H Bergis; K Federlin; R G Bretzel Journal: Horm Metab Res Date: 1997-10 Impact factor: 2.936
Authors: Leona Plum; Hua V Lin; Roxanne Dutia; Jun Tanaka; Kumiko S Aizawa; Michihiro Matsumoto; Andrea J Kim; Niamh X Cawley; Ji-Hye Paik; Y Peng Loh; Ronald A DePinho; Sharon L Wardlaw; Domenico Accili Journal: Nat Med Date: 2009-09-20 Impact factor: 53.440
Authors: Kristina I Rother; Lisa M Spain; Robert A Wesley; Benigno J Digon; Alain Baron; Kim Chen; Patric Nelson; H-Michael Dosch; Jerry P Palmer; Barbara Brooks-Worrell; Michael Ring; David M Harlan Journal: Diabetes Care Date: 2009-10-06 Impact factor: 19.112
Authors: Ellen Kraig; Leslie A Linehan; Hanyu Liang; Terry Q Romo; Qianqian Liu; Yubo Wu; Adriana D Benavides; Tyler J Curiel; Martin A Javors; Nicolas Musi; Laura Chiodo; Wouter Koek; Jonathan A L Gelfond; Dean L Kellogg Journal: Exp Gerontol Date: 2018-02-03 Impact factor: 4.032
Authors: S Alice Long; Mary Rieck; Srinath Sanda; Jennifer B Bollyky; Peter L Samuels; Robin Goland; Andrew Ahmann; Alex Rabinovitch; Sudeepta Aggarwal; Deborah Phippard; Laurence A Turka; Mario R Ehlers; Peter J Bianchine; Karen D Boyle; Steven A Adah; Jeffrey A Bluestone; Jane H Buckner; Carla J Greenbaum Journal: Diabetes Date: 2012-06-20 Impact factor: 9.461