Introduction & Objective: Patients with Type 1 Diabetes (T1D) have altered brain functional connectivity (FC) at resting state, particularly in attention and decision-making brain regions. Recent studies have shown that assessing FC during a cognitive task may be more predictive of individual traits and function. In this study, we investigate how FC within the salience network (SAL), which integrates brain responses to external stimuli, is altered when patients with T1D perform cognitive tasks during euglycemia and mild hypoglycemia.

Method: Thirty-one subjects (20 T1D, 11M/9F, age 37 ± 13 yrs; BMI 27.4 ± 5.4 HbA1c 7.6 ± 0.9 %) and (11 HC, 4M/7F, age 30 ± 8 yrs; BMI 24.9 ± 2.9, HbA1c ± 5.3 ± 0.3%) completed a 2-step hyperinsulinemic-euglycemic (90 mg/dl)-hypoglycemic (60 mg/dl) clamp both at rest and during three tasks: 2-back  (working memory), card guess (reward), and gradual-onset continuous performance (gradCPT; sustained attention). After standard preprocessing, pairwise FC between the nodes of the Salience (SAL) network (Left and Right anterior insula, dorsal anterior cingulate cortex) was calculated. FC in the SAL network was defined as the average of these pairwise values.

Results: Patients with T1D had lower FC during hypoglycemia in the SAL network compared to HC during resting state (P<0.009) as well as 2-back (P<0.024), Card Guess (P<0.036), and gradCPT (P<0.036) tasks. There were no significant relationships between FC and counterregulatory hormones.

Conclusion: Compared to HC, patients with T1D have lower FC in the SAL network during mild hypoglycemia while performing memory, attention and reward stimulating cognitive tasks. These findings suggest an important role for the SAL network in integrating brain responses during hypoglycemia.

Disclosure

E. Sanchez Rangel: None. R. Belfort-DeAguiar: Research Support; Fractyl Health, Inc. C. Lacadie: None. T.J. Chung: None. D. Scheinost: None. G.F. Mason: Consultant; Merck & Co., Inc. J.J. Hwang: None.

Funding

National Institutes of Health (R01DK123227)

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