A Pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes

• Published in: Nature communications 2022-08, Vol.13 (1), p.4940-14, Article 4940
• Main Authors: Reiss, Allan L., Jo, Booil, Arbelaez, Ana Maria, Tsalikian, Eva, Buckingham, Bruce, Weinzimer, Stuart A., Fox, Larry A., Cato, Allison, White, Neil H., Tansey, Michael, Aye, Tandy, Tamborlane, William, Englert, Kimberly, Lum, John, Mazaika, Paul, Foland-Ross, Lara, Marzelli, Matthew, Mauras, Nelly
• Format: Article
• Language: English
• Subjects: 59/36; 59/57; 631/378/2571; 692/163/2743/137/1418; Adolescent; Adolescents; Anisotropy; Assessments; Blood Glucose; Brain; Brain research; Child; Children; Closed loops; Cognition; Cognitive ability; Criteria; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - drug therapy; Disease control; Functional anatomy; Glucose; Health care facilities; Health risks; Humanities and Social Sciences; Humans; Hybrid systems; Hypoglycemic Agents - therapeutic use; Insulin; Insulin - therapeutic use; Insulin Infusion Systems; Intelligence; Medical imaging; Medical research; multidisciplinary; Neuroimaging; Perceptual reasoning; Pilot Projects; Randomization; Science; Science (multidisciplinary); Structure-function relationships; Substantia alba; Substantia grisea; Surface area; Teenagers; Thickness
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-32289-x

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system. Eligibility criteria for participation in the study included age between 14 and 17 years and a diagnosis of T1D before 8 years of age. Randomization to either a hybrid closed-loop or standard diabetes care group was performed after pre-qualification, consent, enrollment, and collection of medical background information. Of 46 participants assessed for eligibility, 44 met criteria and were randomized. Two randomized participants failed to complete baseline assessments and were excluded from final analyses. Participant data were collected across five academic medical centers in the United States. Research staff scoring the cognitive assessments as well as those processing imaging data were blinded to group status though participants and their families were not. Forty-two adolescents, 21 per group, underwent cognitive assessment and multi-modal brain imaging before and after the six month study duration. HbA1c and sensor glucose downloads were obtained quarterly. Primary outcomes included metrics of gray matter (total and regional volumes, cortical surface area and thickness), white matter volume, and fractional anisotropy. Estimated power to detect the predicted treatment effect was 0.83 with two-tailed, α = 0.05. Adolescents in the hybrid closed-loop group showed significantly greater improvement in several primary outcomes indicative of neurotypical development during adolescence compared to the standard care group including cortical surface area, regional gray volumes, and fractional anisotropy. The two groups were not significantly different on total gray and white matter volumes or cortical thickness. The hybrid closed loop group also showed higher Perceptual Reasoning Index IQ scores and functional brain activity more indicative of neurotypical development relative to the standard care group (both secondary outcomes). No adverse effects associated with study participation were observed. These results suggest that alterations to the developing brain in T1D might be preventable or reversible wit