Posttransplant Diabetes Mellitus in Kidney Transplant Recipients Receiving Calcineurin or mTOR Inhibitor Drugs

Abstract

The mean follow-up was 39.2 (range 9.0-103.8) months. Overall, the number of patients needing insulin was 7.4% (39/528). The incidences for Groups I, II, and III of 7.6%, 11.7%, and 5.9%, respectively, were not statistically different. Characteristics of patients with PTDM included older age (P=0.007); greater body weight (kg) at transplant, 6 months, and 12 months, respectively (P<0.001); greater BMI (kg/m2) at transplant, 6 months, and 12 months, respectively (P<0.001); more acute rejection episodes 28.2% vs. 13.5% (P=0.012); and increased incidence in African Americans (P=0.03). Multivariable analysis demonstrated increased risk for PTDM (defined as new insulin use) for tacrolimus, (hazard ratio [HR] 3.794, P=0.007); treated rejections (HR 2.491, P=0.0115); age (HR 1.407, P=0.0116); and BMI (HR 1.153, P<0.0001). New insulin use occurred sooner and with less total glucocorticoid dose for tacrolimus patients. If PTDM is defined as all cases of new hyperglycemia, then no immunosuppressive drug group demonstrated an increased risk. CONCLUSION.: The risk for developing PTDM is greatest among older recipients, and those obese at the time of transplant; those given steroid pulse therapy were at exceptionally high-risk. PTDM risk reduction should focus on weight loss in the obese end-stage renal disease population prior to transplant.

The Pharmacodynamic Effects of Sirolimus andSirolimus-Calcineurin Inhibitor Combinations on Macrophage Scavenger and Nuclear Hormone Receptors

“…22 In renal transplant recipients, a high rate of post-transplant diabetes mellitus (PTDM) is most commonly attributed to TAC ($12%), followed by CsA ($8%), and sirolimus ($6%). 23 When used in combination, SIR/CsA had a higher 1-year rate of PTDM (33%) than SIR/ TAC (17%) or mycophenolate mofetil (MMF)/TAC (14%, p ¼ 0.06) in a recent study, which was unexpected but supported our findings. 8 Increased PTDM with SIR/CsA was confirmed in another study, in which SIR/CsA plus steroids had a higher incidence of PTDM (32%) than CsA plus steroids (10%, p ¼ 0.0144).…”

Everolimus Induces Rapid Plasma Glucose Normalization in Insulinoma Patients by Effects on Tumor As Well As Normal Tissues

“…This occurs also in cancer patients and transplant patients on mTOR inhibitors [2, 20 -22]. Nine percent of the neuroendocrine patients experienced plasma glucose levels above 13.9 mmol/L [2]; in renal transplant patients that receive lower everolimus doses, this was 5.9% [23]. However, even in renal transplant patients treated with the mTOR inhibitor sirolimus, the oral glucose tolerance test showed already a 30% increase in incidence of impaired glucose tolerance [20].…”

Prevalence of Metabolic Syndrome in Organ Transplantation: A Review of the Literature

“…Sustained activation of mTORC1 is a major cause for nutrient-induced obesity and insulin resistance [134]. So, theoretically, sirolimus could be useful in the management of obesity or T2DM through the deactivation of the negative-feedback loop of the mTOR pathway in adipose tissue, liver and muscle [135][136][137]. However, data in the literature are controversial and a growing body of evidence suggests that sirolimus may also be diabetogenic.…”

“…However, Araki et al. [136] did not find the increased risk of NODAT with de novo sirolimus use and sirolimus-based immunosuppression therapy in renal transplant recipients.…”