Background: The effect of dysglycemia on brain development and cognition is not well understood.

Methods: In a multi-site study, we examined brain activation in 93 children with T1D (mean age 11.5 ± 1.8 years) and 57 nondiabetic children (mean age 11.8 ± 1.5 years) as they performed a classic executive function paradigm, the Go/No-Go task. Participants responded to letters flashed on a screen by a key press (Go) but not to the letter X (No-Go).

Results: Despite similar task performance between the groups, children with T1D exhibited greater activation in executive control regions (dorsal anterior cingulate cortex, inferior frontal gyri, cerebellum and supramarginal gyri; p=0.010) and less suppression in the posterior node of the default mode network (DMN) compared to controls (p=0.006). Secondary analyses showed greater activation in executive control regions was associated in T1D with shorter response times and better parent-reported measures of executive function (ps<0.046). Less suppression of the DMN was correlated with slower processing speed (p=0.049), higher lifetime HbA1c levels (p=0.031), higher HbA1c at scan (p=0.034), and earlier age of T1D onset (p=0.040). Finally, within the T1D (but not control) group, greater activation in executive control regions was associated with less suppression of the DMN (p=0.006).

Conclusion: These findings suggest that compensatory recruitment of executive control areas may act to offset T1D-related impairments in the DMN and, at least transiently, allow behavioral performance on Go/No-Go to be equivalent to that of nondiabetic controls.


L.C. Foland-Ross: None. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care. N. Mauras: Consultant; Self; Novo Nordisk Inc., PicoLife. Research Support; Self; Medtronic MiniMed, Inc. A. Arbelaez: None. N.H. White: None. T. Aye: None. D.M. Wilson: Advisory Panel; Self; Tolerion, Inc. Research Support; Self; Beta Bionics, Dexcom, Inc., Medtronic. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited. S.A. Weinzimer: Consultant; Self; Eli Lilly and Company, Sanofi. Consultant; Spouse/Partner; Tandem Diabetes Care. Consultant; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Stock/Shareholder; Self; InsuLine Medical Ltd. E. Tsalikian: None. M. Tansey: Advisory Panel; Self; Daiichi Sankyo Company, Limited. A. Cato: None. T. Hershey: Research Support; Spouse/Partner; Sage Pharmaceuticals. L.A. Fox: None. G. Tong: None. K.A. Englert: Consultant; Self; PicoLife Technologies, LLC. P. Mazaika: None. A.L. Reiss: None.


Eunice Kennedy Shriver National Institute of Child Health and Human Development (DIRECNET: U01HD-41906, HD-41908, HD-41915, HD-41918, HD-56526, R01HD078463, U54HD087011; National Center for Advancing Translational Sciences (UL1TR000448)

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