Diabetes in People With Tuberous Sclerosis Complicated Handled With mTOR Inhibitors


This article was originally published here

Pediatr Neurol. 2021, April 2; 120: 7-10. doi: 10.1016 / j.pediatrneurol.2021.03.007. Online before printing.


BACKGROUND: Tuberous Sclerosis Complex (TSC) is a genetic disorder that manifests itself in several body systems. A mammalian rapamycin (mTOR) inhibitor (mTORi) target, either everolimus or sirolimus, is now routinely prescribed for several clinical manifestations of TSC, including giant subependymal cell astrocytoma and epilepsy. These drugs are generally well tolerated. Side effects previously identified in well-designed clinical studies are usually mild and easy to manage. The regulatory approvals for the treatment of TSC have expanded the clinical use of everolimus and sirolimus, broadened the clinician’s experience, and enabled the identification of potential treatment-related effects that are less common than seen or detected in previous clinical trials.

METHODS: The medical records of clinical patients from our TSC center who were treated with an mTORi and later developed diabetes mellitus (DM) were analyzed and compared to those who were not treated with an mTORi. Eight people received a detailed analysis, including laboratory results, concomitant medications, and body mass indexes.

Results: Among the 1576 people with TSC, 4% who took an mTORi developed diabetes compared to 0.6% of those who did not receive the mTORi, showing a significant interaction between DM and mTORi (chi-square = 18.1, P <0.001). Details of eight patients who developed DM were presented.

CONCLUSIONS: Long-term use of mTORi agents in TSC can lead to a risk of diabetes. Early detection can be critical in management. Additional studies are needed to further investigate a causal relationship. However, clinicians should be aware of this possible link when initiating and monitoring ongoing treatment.

PMID: 33962348 | DOI: 10.1016 / j.pediatrneurol.2021.03.007