Does increasing insulin resistance in adolescence actively decrease cerebral perfusion to oral glucose tolerance test?

Background: Approximately 20% of American adolescents are obese, and nearly half demonstrate some form of insulin resistance (IR). Insulin acts as a metabolic hormone, a neurotrophic growth factor, and a vasodilator. Notably, adults with neurologic disease often exhibit IR and reduced cerebral blood flow (CBF). Adolescent brains are actively growing such that IR may negatively impact brain health in part due to lower brain perfusion. Specifically, given the role of insulin as a potential vasodilator, we hypothesized CBF would increase in response to a physiologic glucose-insulin surge, but this effect would lessen as IR level increased. Methods: Adolescents (n=11, 3 females, age=14.8±2 yr, BMI=24.7±7) taking no medications were studied. IR was estimated by calculating HOMA-IR using fasting glucose and insulin, spanning a spectrum of IR (excluding diabetes). Subjects completed a magnetic resonance imaging (MRI) study visit to assess cerebral perfusion using arterial spin labeling (ASL). Heart rate (HR), mean arterial pressure (MAP) and end tidal CO 2 (ETCO 2 ) were assessed at baseline and during oral glucose tolerance test (OGTT); ingesting 75g glucose in 296mL water (Trutol). Venous blood was sampled at baseline and 5, 10, 20, 30, 45, and 60 minutes post OGTT. Perfusion at peak plasma insulin was compared to baseline. Significance was determined using linear regression of change in perfusion (peak- baseline) versus HOMA-IR and set at p≤0.05. Results: Results are mean±SD. HR (p=0.9), MAP (p=0.22) and ETCO 2 (p=0.75) were similar across HOMA-IR. MAP (p=0.44) and ETCO 2 (p=0.15) did not change during OGTT at insulin peak. Peak insulin occurred at 44±13 min post OGTT (baseline: 8±4 vs. peak: 65±38 μU/mL, p=0.001). Glucose changed from 79±6 to 142±30 mg/dL at peak insulin (p=0.0005). There were no significant associations between HOMA-IR and changes in perfusion in gray matter (R 2 =0.06, p=0.43) and white matter (R 2 =0.07, p=0.13). There were no significant associations for the following regions: hippocampus, amygdala, thalamus, anterior and posterior insula, and precuneus (R 2 all <0.2, p all >0.14). There was a trend toward negative regression in anterior cingulate gyrus (R 2 =0.25, p=0.11). Conclusions: These data suggest an OGTT does not acutely change brain perfusion at a global or regional level in adolescents, except possibly the anterior cingulate gyrus that is negatively impacted by increasing IR. The majority of present findings do not support our hypothesis that OGTT-mediated changes in cerebral perfusion are associated with IR in adolescents. NIH R21HD097510 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.