2078-P: Impact of Hypothalamic Inflammation and Gliosis on Cardiometabolic Risk in Children from the ABCD Study

Introduction and Objective: Mediobasal hypothalamus (MBH) gliosis can be detected in humans by MRI. MBH gliosis is associated with obesity in children and with insulin resistance, type 2 diabetes, hypertension, and dyslipidemia in adults. Whether MBH gliosis is related to elevated cardiometabolic (CM) risk in children is unknown. Methods: Using a case-control design and retrospective approach, we tested for differences in MBH gliosis, measured by brain MRI obtained 2yrs prior to the first assessments of CM risk factors in ABCD Study. Evidence of MBH gliosis was assessed by measuring mean bilateral MBH/Amygdala (Amy) T2 signal ratio. Putamen/Amy ratio was used as a negative control measure. From 301 eligible participants (11-13yo), 60 children were classified as cases (≥ 2 of 4 CM risk factors [overweight/obesity, prediabetes, dyslipidemia and hypertension]) and n=147 children with no CM risk factors as controls. Cases had most frequently overweight/obesity (93%), followed by dyslipidemia. Results: At baseline, cases and controls did not differ on mean age, sex, pubertal stage, and study site distributions. Per design, cases had higher BMI z-score (1.74±0.59 vs -0.01±0.66), total cholesterol (173±29 vs 144±20 mg/dL) and hemoglobin A1c levels (5.3±0.4 vs 5.1±0.3 %). Compared to controls, cases had higher MBH/Amy T2 signal ratio 2yrs earlier (β=0.03, P=0.046, adjusted for site) but did not differ in their negative T2 control ratio (β=0.01, P=0.072). When investigating MBH gliosis and individual CM risk factors, children with overweight or obesity (n=117), and children with pre-diabetes (n=14) had greater MBH/Amy T2 signal ratio 2yrs earlier than children with healthy weight (n=184, β=0.02, P=0.048) and those without prediabetes (n=287, β=0.05, P=0.041, adjusted for BMI z-score and site), respectively. Conclusion: Children with CM risk factors show greater evidence of hypothalamic gliosis 2yrs earlier. As further data is released, future studies should test whether the degree of MBH gliosis predicts incident metabolic syndrome or prediabetes in children. Disclosure L. Esposito Sewaybricker: Consultant; Ended; NodThera Limited. S. Kee: None. S. Melhorn: None. E.S. Schur: Consultant; Ended; Amgen Inc. Funding American Heart Association (#929228), University of Washington Nutrition and Obesity Research Center (P30DK035816), National Institutes of Health (R01DK134417, R01DK133356, R01DK144233, K24HL144917)