Missed meal boluses and poorer glycemic control impact on neurocognitive function may be associated with white matter integrity in adolescents with type 1 diabetes

Edna Litmanovitch, Ronny Geva, Avital Leshem, Mirit Lezinger, Eli Heyman, Maor Gidron, Jessica Yarmolovsky, Efrat Sasson, Sigal Tal, Marianna Rachmiel

Research output: Contribution to journalArticlepeer-review


Background: The notion that pediatric type 1 diabetes impacts brain function and structure early in life is of great concern. Neurological manifestations, including neurocognitive and behavioral symptoms, may be present from childhood, initially mild and undetectable in daily life. Despite intensive management and technological therapeutic interventions, most pediatric patients do not achieve glycemic control targets for HbA1c. One of the most common causes of such poor control and frequent transient hyperglycemic episodes may be lifestyle factors, including missed meal boluses. Objective: The aim of this study was to assess the association between specific neurocognitive accomplishments—learning and memory, inhibition ability learning, and verbal and semantic memory—during meals with and without bolusing, correlated to diffusion tensor imaging measurements of major related tracts, and glycemic control in adolescents with type 1 diabetes compared with their healthy siblings of similar age. Study design and methods: This is a case–control study of 12- to 18-year-old patients with type 1 diabetes (N = 17, 8 male patients, diabetes duration of 6.53 ± 4.1 years) and their healthy siblings (N = 13). All were hospitalized for 30 h for continuous glucose monitoring and repeated neurocognitive tests as a function of a missed or appropriate pre-meal bolus. This situation was mimicked by controlled, patient blinded manipulation of lunch pre-meal bolus administration to enable capillary glucose level of <180 mg/dl and to >240 mg/d 2 hours after similar meals, at a similar time. The diabetes team randomly and blindly manipulated post-lunch glucose levels by subcutaneous injection of either rapid-acting insulin or 0.9% NaCl solution before lunch. A specific neurocognitive test battery was performed twice, after each manipulation, and its results were compared, along with additional neurocognitive tasks administered during hospitalization without insulin manipulation. Participants underwent brain imaging, including diffusion tensor imaging and tractography. Results: A significant association was demonstrated between glycemic control and performance in the domains of executive functions, inhibition ability, learning and verbal memory, and semantic memory. Inhibition ability was specifically related to food management. Poorer glycemic control (>8.3%) was associated with a slower reaction time. Conclusion: These findings highlight the potential impairment of brain networks responsible for learning, memory, and controlled reactivity to food in adolescents with type 1 diabetes whose glycemic control is poor.

Original languageEnglish
Article number1141085
JournalFrontiers in Endocrinology
StatePublished - 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 Litmanovitch, Geva, Leshem, Lezinger, Heyman, Gidron, Yarmolovsky, Sasson, Tal and Rachmiel.


  • adolescents
  • brain domains
  • cognitive performance
  • diffusion tension imaging
  • glycemic control
  • type 1 diabetes


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