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Endocrine Abstracts (2017) 49 OC6.2 | DOI: 10.1530/endoabs.49.OC6.2

1Endocrinology and Metabolism, IRCCS Policlinico San Donato, San Donato Milanese, Italy; 2Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milano, Italy; 3Department of Internal Medicine, Transplant Medicine Unit, San Raffaele Scientific Institute, Milano, Italy; 4Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.


It has been suggested that the selective m-TOR inhibitor, Rapamycin, has been improved the success pancreatic islet allotransplantation (ITx) in type 1 diabetic patients (T1DM). Forty-one ITx were studied. Thirteen T1DM in poor glycemic control underwent a 45-days Rapamycin before ITx followed by standard Edmonton Protocol (EP, group 1, Milan), and they were compared to 28 T1DM patients undergoing EP (group 2, Miami). Outcome measures were daily insulin requirement (DIR), HbA1c, C-peptide and the SUITO index of beta-cell function before and 1 year after ITx. Four patients from group 1 underwent euglycemic-hyperinsulinemic clamp with 6,6-d2-glucose infusion before and after ITx. We found a significant reduction in DIR after Rapamycin pre-treatment (−8±6 U/day, mean±S.D., P<0.001). Nine patients from group 1 fulfilled follow-up. One year after ITx, DIR significantly decreased (−37±15 U/day, P<0.001) and six patients became insulin independent. We observed greater DIR reduction in group 1 as compared to group 2 at 1-year follow-up (−37±15 vs −19±13 U/day, P=0.005), which remained significant after adjusting for gender, age, glucose and baseline HbA1c (beta coefficient of multivariate regression analysis±S.E. 18.2±5.9, P=0.006). In patients from group 1, HbA1c significantly decreased 1 year after ITx (−2.1±1.4%, P=0.002), while C-peptide (+1.5±0.9, P=0.002), and SUITO index increased (+57.4±39.7, P=0.016). We did not observe differences in change between group 1 and 2 as far as HbA1c, C-peptide and SUITO index are concerned before and after ITx. Hepatic glucose production during the insulin clamp decreased after Rapamycin pre-treatment (−1.1±1.1 mg/kg per min, P=0.04) and after ITx (−1.6±0.6 mg/kg per min, P=0.015), while no changes in peripheral glucose disposal were observed during Rapamycin treatment. In conclusion, Rapamycin contributes to improve metabolic control also enhancing hepatic insulin sensitivity after ITx. Rapamycin pre-treatment may improve ITx success rate by reduction of pre-transplant DIR and increase of hepatic insulin sensitivity.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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