Effects of non-steroid immunosuppressive drugs on insulin secretion in transplantation

Annales d'endocrinologie
M-C VantyghemC Noël


Post-transplantation diabetes (PTD) is a serious complication in organ transplantation: not only does it increase the risk of graft dysfunction; it also increases cardiovascular morbidity and mortality. PTD incidence is correlated with age, non-Caucasian ethnic background, a family history of diabetes, excess weight, hepatitis C infection and steroid boluses for potential rejection. Different mechanisms might explain post-transplantation glucose metabolism disorders: ischemia-reperfusion disorders, whether renal, hepatic or cardiac, are responsible for insulin-resistance, which is increased by post-transplantation steroids; the detrimental effect of non-steroid immunosuppressive drugs on insulin-secretion could also be involved, especially with calcineurin inhibitors. In vivo and in vitro studies have shown that tacrolimus has inhibitory effects on insulin-secretion, while these effects are less obvious for cyclosporin, and were mainly demonstrated in vitro. Mycophenolate has no overt effect on insulin-secretion. Sirolimus and everolimus, two mTOR inhibitors, have shown controversial results in this realm. The effects of sirolimus (most often studied mTOR inhibitor) appear to depend on serum levels, cell type (ss cell or cell l...Continue Reading


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