Diabetes in individual with Tuberous Sclerosis Complex treated with mTOR inhibitors

ABSTRACT: Background Tuberous sclerosis complex (TSC) is a genetic disorder that is manifested in multiple body systems. Initiation of an mTOR inhibitor, either everolimus or sirolimus, are now routinely prescribed for multiple clinical manifestations of TSC, including subependymal giant cell astrocytoma and epilepsy. These medications are generally well tolerated. Side effects previously identified in well-designed clinical trials tend to be mild in severity and are readily manageable. Regulatory approvals for; the treatment of TSC have expanded and use of everolimus and sirolimus; clinically, enlarging clinician experience and enabling identification of additional; potential treatment-related effects that are rarer than could be identified or recognized; in previous clinical trials Methods The medical records of clinical patients from our TSC center who were treated with an mTOR inhibitor and later developed diabetes mellitus (DM) were analyzed and compared to those who were not treated with an mTORi. Eight received detailed analysis, including laboratory results, concomitant medications and body mass indices. Results Of the 1576 , 4 % taking an mTORi developed diabetes compared to 0.6% of those not on mTORi showing that a significant interaction between DM and mTORi (Chi Square= 18.1, p Conclusion The long-term use of mTOR inhibitors in TSC may contribute to diabetes risk. Early detection can be critical in management. Future studies would be necessary to demonstrate a causal relationship, but clinicians should be aware of this possible implication when educating families, initiating and monitoring ongoing treatment.