PMID- 33962348
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220202
IS  - 1873-5150 (Electronic)
IS  - 0887-8994 (Linking)
VI  - 120
DP  - 2021 Jul
TI  - Diabetes in Individuals With Tuberous Sclerosis Complex Treated With mTOR 
      Inhibitors.
PG  - 7-10
LID - S0887-8994(21)00053-9 [pii]
LID - 10.1016/j.pediatrneurol.2021.03.007 [doi]
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder that is 
      manifested in multiple body systems. A mammalian target of rapamycin (mTOR) 
      inhibitor (mTORi), either everolimus or sirolimus, is 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 
      and readily manageable. Regulatory approvals for the treatment of TSC have 
      expanded the use of everolimus and sirolimus clinically, enlarging clinician 
      experience and enabling identification of 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 mTORi and later developed diabetes mellitus (DM) were 
      analyzed and compared with those who were not treated with an mTORi. Eight 
      individuals received detailed analysis, including laboratory results, concomitant 
      medications, and body mass indices. RESULTS: Among the 1576 individuals with TSC, 
      4% taking an mTORi developed diabetes compared with 0.6% of those not on 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: The long-term use of mTORi agents in TSC may contribute to a risk of 
      diabetes. Early detection can be critical in management. Additional studies are 
      need to further investigate a causal relationship, but clinicians should be aware 
      of this possible association when initiating and monitoring ongoing treatment.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Agricola, Karen
AU  - Agricola K
AD  - Department of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio. Electronic address: Karen.Agricola@cchmc.org.
FAU - Stires, Gabrielle
AU  - Stires G
AD  - Department of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio.
FAU - Krueger, Darcy A
AU  - Krueger DA
AD  - Department of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio; Department of Neurology, University of Cincinnati College of 
      Medicine, Cincinnati, Ohio.
FAU - Capal, Jamie K
AU  - Capal JK
AD  - Department of Neurology, University of North Carolina at Chapel Hill, Chapel 
      Hill, North Carolina.
FAU - Franz, David N
AU  - Franz DN
AD  - Department of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio; Department of Neurology, University of Cincinnati College of 
      Medicine, Cincinnati, Ohio.
FAU - Ritter, David M
AU  - Ritter DM
AD  - Department of Neurology, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio; Department of Neurology, University of Cincinnati College of 
      Medicine, Cincinnati, Ohio.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210402
PL  - United States
TA  - Pediatr Neurol
JT  - Pediatric neurology
JID - 8508183
RN  - 0 (MTOR Inhibitors)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Child
MH  - Diabetes Mellitus/*chemically induced
MH  - Everolimus/*adverse effects
MH  - Female
MH  - Humans
MH  - MTOR Inhibitors/*adverse effects
MH  - Male
MH  - Sirolimus/*adverse effects
MH  - Tuberous Sclerosis/*drug therapy
OTO - NOTNLM
OT  - Adverse events
OT  - Diabetes mellitus
OT  - Tuberous sclerosis
OT  - mTOR inhibitors
EDAT- 2021/05/08 06:00
MHDA- 2022/02/03 06:00
CRDT- 2021/05/07 20:36
PHST- 2020/12/01 00:00 [received]
PHST- 2021/03/18 00:00 [revised]
PHST- 2021/03/19 00:00 [accepted]
PHST- 2021/05/08 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/05/07 20:36 [entrez]
AID - S0887-8994(21)00053-9 [pii]
AID - 10.1016/j.pediatrneurol.2021.03.007 [doi]
PST - ppublish
SO  - Pediatr Neurol. 2021 Jul;120:7-10. doi: 10.1016/j.pediatrneurol.2021.03.007. Epub 
      2021 Apr 2.