1175-P: Putative Neuroinflammation and Smaller Brain Volumes in Youth with Obesity and Dysglycemia

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Introduction and Objective: Youth-onset T2D follows a more aggressive course than adult-onset. While brain health is at risk in adults, the effects in youth are not well understood. This study aimed to determine if overweight/obesity with or without dysglycemia is associated with brain structural differences and putative neuroinflammation in youth. Methods: This two-site cross-sectional study included 3 groups of youth ages 12-17y: with normal weight and normal glucose tolerance (NW-NGT), overweight/obesity and NGT (O-NGT), and overweight/obesity with dysglycemia (O-DG). Brain measures via magnetic resonance imaging (MRI) included putative neuroinflammation (diffusion basis spectrum imaging restricted fraction, DBSI-RF, modeled on diffusion MRI) and volumes (FreeSurfer v7.3.2 on T1 weighted MRI). Cognitive function was assessed with the NIH Toolbox Cognition Battery. Outcome measures were compared using a one-way ANCOVA covarying age and sex with Bonferroni adjustment for multiple comparisons and post-hoc t-tests for significant main effects of group. Results: Groups did not differ in age, sex, cognition, Tanner stage, SES, parental IQ, or head motion during scanning (p’s>.05). There was a main effect of group (p<.001) on mean DBSI-RF across all white matter (WM) tracts; post hoc O-NGT (n=34) and O-DG (n=24) groups > NW-NGT (n=32) group, p<.05. There were main effects of group for nucleus accumbens (NAc) volume (p<.001; O-NGT [n=38] and O-DG [n=30] groups < NW-NGT [n=33] group, p<.05) and total cortical WM volume (p<.01; O-NGT < NW-NGT group, p<.05). Conclusion: Youth with overweight/obesity have elevated putative neuroinflammation across WM tracts and lower volume in the NAc, a region associated with motivation/reward processing, and total cortical WM. Dysglycemia does not seem to have an additive effect over and above overweight/obesity. Prospective future work will determine if these brain differences change with time or with change in metabolic or weight status. Disclosure M. Jansen: None. H. Lugar: None. J. Rutlin: None. M. Ray: None. A. Crosby: None. Z. Li: Stock/Shareholder; Immunome, Viking Therapeutics, Pfizer Inc, Vir Biotechnology. Research Support; National Institutes of Health. A. Arbelaez: None. M. Vajravelu: None. S.A. Arslanian: None. T. Hershey: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK126826-04)

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