Effects of different immunosuppressive drugs on incretins in renal transplant patients

EFFECTS OF DIFFERENT IMMUNOSUPPRESSIVE DRUGS ON INCRETINS IN RENAL TRANSPLANT PATIENTS Incretin system has an important role in the pathogenesis of diabetes mellitus. Post-transplant diabetes, associated with antirejection medications especially including calcineurin inhibitors and is a major problem affect graft survival. Immunosuppressive drugs used in transplantation patients, may contribute to the development of post-transplant diabetes mellitus through their possible adverse effects on incretins. In this study, we aimed to compare the effects of different immunosuppressive drugs used in renal transplantation patients, on incretins. 15 cyclosporine-treated renal transplant patients, 15 tacrolimus-treated renal transplant patients and 15 healthy volunteers as a control group, a total of 45 people with no history of diabetes were enrolled in the study. Oral glucose tolerance test with 75 gr glucose was performed to all patients. Glucagon-like peptide 1 (GLP-1), and Glucose-dependent Insulinotropic Polypeptide (GIP) were measured at 0, 30, 60, 90, 120 minutes. Among three groups, at 0, 30 and 120 minutes statistically significant difference on GLP-1 levels was observed (respectively, p <0.001, p = 0.026 and p <0.001). Baseline GLP-1 levels in both cyclosporine and tacrolimus groups was higher than the control group (respectively, p <0.001 and p = 0.033). Basal GLP-1 levels were significantly higher in cyclosporine group, compared to the tacrolimus group, (p = 0.003). At 30 and 90 minutes, GLP-1 levels were significantly higher in tacrolimus group compared to cyclosporine group (p = 0.009 and p = 0.042, respectively). GLP-1 levels at 120 minutes were significantly higher in the cyclosporin group compared to the tacrolimus group (p = 0.01). While reaching peak GLP-1 levels at 30 minutes in the tacrolimus and control group, the highest levels of GLP-1 in cyclosporine group was achieved at 120 minutes. Among three groups GIP levels at 120 minutes statistically significant difference was found (p = 0.005). Between the cyclosporine group and the control group GIP levels at 30, 60, 90 and 120 minutes revealed statistically significant difference (respectively p = 0.04, p = 0.049, p = 0.040 and p = 0.002). The difference between maximum GLP-1 levels and basal GLP-1 levels (ΔGLP-1), revealed statistically significant difference among three groups (p <0.0001). When compared with cyclosporine group, control and tacrolimus group had a statistically significant difference in the terms of ΔGLP-1 (respectively, p <0.0001 and p = 0.003). The difference between the maximum and the basal levels of GIP (ΔGIP) was statistically significant among three groups (p = 0.029). These findings showed that tacrolimus-treated renal transplant patients had preserved GLP-1 response to oral glucose load and cyclosporin-treated ones had higher baseline GLP-1 levels and atrophied and temporally impaired GLP-1 response to the oral glucose load. Key words: Incretin, GLP-1, GIP, post-transplant diabetes, renal transplantation.