ECE2013 Oral Communications Diabetes & Obesity (6 abstracts)
Reduction of fat mass with the mTOR inhibitor, sirolimus, in humans: from transplantation to lipodystrophies
Emilie Parent 1 , François Pattou 1, , Olivier Ernst 1 , Georges Lion 1 , Isabelle Wolowczuk 2 , Olivier Dharancy 1 , Christian Noel 1 , Julie Kerr-Conte 3 & Marie-Christine Vantyghem 1,
1Regional University Hospital, Lille, France; 2Pasteur institute, UMR 8199, Lille, France; 3INSERM UMR 859, Lille, France.
Objectives: Sirolimus inhibits adipocyte differentiation (Yeh PNAS 1995). This study compares weight and fat markers in two groups of patients treated or not with sirolimus, before and after transplantation.
Patients and method: Nineteen islet-alone transplanted patients treated with sirolimus and 7 islet-alone or liver-transplanted patients NOT treated with sirolimus were compared 1 year after transplantation in terms of weight, fat mass (equation of body fat and percentage of fat mass by DEXA), and metabolic parameters. 14/19 islet-alone transplanted patients treated with sirolimus were reassessed 5 years post-transplantation.
Results: Before transplantation, the metabolic and weight/fat parameters were similar in the 2 groups except for C-peptide. One year post-transplantation, body fat and leptin reduction was more important in the sirolimus than in the NON-sirolimus group (P<0.05). Leptin levels were lower in the sirolimus group (P=0.01). Compared to pre-transplant values, one year post-transplantation, weight, fat mass and metabolic parameters did not change in the NON-sirolimus group while the sirolimus group showed a significant reduction in weight (P<0.001), BMI (P<0.001), body fat (P<0.001), percentage of body (P<0.05) and truncal (P<0.05) fat mass, HbA1c levels (P<0.001) and ßscore (P<0.01). Compared to pre-transplant values, the sirolimus group showed a significant reduction of leptin level one (P=0.004) and five years (P=0.01) post-transplantation, as well as a persistent reduction of HbA1c (before: 8.4 (1.5); 1-year: 5.8 (1.7); 5-years 6.7 (1.7)% and ß score (before: 0.0; 1-year: 7.0 (3.5); 5-years 4.0 (4.0)) (P<0.05). Sirolimus correlated with leptin (r=−0.22, P=0.018) and body fat mass (r=−0.18, P=0.03).
Conclusion: These results suggest that sirolimus modulates the amount and/or the quality of adipose tissue and innate immunity, opening new perspectives both in the choice of immuno-suppressant, and the treatment of nucleopathies, especially lipodystrophies (Ramos Sci Transl Med 2012).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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