Executive task-based brain function in children with type 1 diabetes: An observational study

Autoři: Lara C. Foland-Ross aff001;  Bruce Buckingam aff002;  Nelly Mauras aff003;  Ana Maria Arbelaez aff004;  William V. Tamborlane aff005;  Eva Tsalikian aff006;  Allison Cato aff007;  Gabby Tong aff001;  Kimberly Englert aff003;  Paul K. Mazaika aff001;  Allan L. Reiss aff001
Působiště autorů: Center for Interdisciplinary Brain Sciences Research, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, United States of America aff001;  Division of Pediatric Endocrinology and Diabetes, Stanford University School of Medicine, Stanford, California, United States of America aff002;  Division of Endocrinology, Diabetes and Metabolism, Nemours Children’s Health System, Jacksonville, Florida, United States of America aff003;  Division of Endocrinology, Washington University, Saint Louis, Missouri, United States of America aff004;  Division of Endocrinology, Yale University, New Haven, Connecticut, United States of America aff005;  Division of Endocrinology, University of Iowa, Iowa City, Iowa, United States of America aff006;  Division of Neurology, Nemours Children’s Health System, Jacksonville, Florida, United States of America aff007;  Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America aff008;  Department of Radiology, Stanford University School of Medicine, Stanford, California, United States of America aff009
Vyšlo v časopise: Executive task-based brain function in children with type 1 diabetes: An observational study. PLoS Med 16(12): e32767. doi:10.1371/journal.pmed.1002979
Kategorie: Research Article
doi: 10.1371/journal.pmed.1002979



Optimal glycemic control is particularly difficult to achieve in children and adolescents with type 1 diabetes (T1D), yet the influence of dysglycemia on the developing brain remains poorly understood.

Methods and findings

Using a large multi-site study framework, we investigated activation patterns using functional magnetic resonance imaging (fMRI) in 93 children with T1D (mean age 11.5 ± 1.8 years; 45.2% female) and 57 non-diabetic (control) children (mean age 11.8 ± 1.5 years; 50.9% female) as they performed an executive function paradigm, the go/no-go task. Children underwent scanning and cognitive and clinical assessment at 1 of 5 different sites. Group differences in activation occurring during the contrast of “no-go > go” were examined while controlling for age, sex, and scan site. Results indicated that, despite equivalent task performance between the 2 groups, children with T1D exhibited increased activation in executive control regions (e.g., dorsolateral prefrontal and supramarginal gyri; p = 0.010) and reduced suppression of activation in the posterior node of the default mode network (DMN; p = 0.006). Secondary analyses indicated associations between activation patterns and behavior and clinical disease course. Greater hyperactivation in executive control regions in the T1D group was correlated with improved task performance (as indexed by shorter response times to correct “go” trials; r = −0.36, 95% CI −0.53 to −0.16, p < 0.001) and with better parent-reported measures of executive functioning (r values < −0.29, 95% CIs −0.47 to −0.08, p-values < 0.007). Increased deficits in deactivation of the posterior DMN in the T1D group were correlated with an earlier age of T1D onset (r = −0.22, 95% CI −0.41 to −0.02, p = 0.033). Finally, exploratory analyses indicated that among children with T1D (but not control children), more severe impairments in deactivation of the DMN were associated with greater increases in hyperactivation of executive control regions (T1D: r = 0.284, 95% CI 0.08 to 0.46, p = 0.006; control: r = 0.108, 95% CI −0.16 to 0.36, p = 0.423). A limitation to this study involves glycemic effects on brain function; because blood glucose was not clamped prior to or during scanning, future studies are needed to assess the influence of acute versus chronic dysglycemia on our reported findings. In addition, the mechanisms underlying T1D-associated alterations in activation are unknown.


These data indicate that increased recruitment of executive control areas in pediatric T1D may act to offset diabetes-related impairments in the DMN, ultimately facilitating cognitive and behavioral performance levels that are equivalent to that of non-diabetic controls. Future studies that examine whether these patterns change as a function of improved glycemic control are warranted.

Klíčová slova:

Attention – Behavior – Blood sugar – Cognitive impairment – Functional magnetic resonance imaging – Glucose – Neuroimaging


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