Impact of increasing insulin resistance on cerebral perfusion in adolescents

Abstract

Background: Adolescence is a key growth period that heavily influences future brain health. Approximately 1 in 5 adolescents are obese in the US, and up to half of them exhibit some form of insulin resistance (IR). Notably, insulin acts as a metabolic hormone, a neurotrophic growth factor, and a vasodilator. Reduced vasodilation may lead to reduced cerebral perfusion, and lower perfusion in older adults is associated with reduced cognition and increased risk of stroke and neurologic disease. Given this background, IR may negatively impact adolescent brain health in part due to lower brain perfusion. Therefore, we hypothesized cerebral perfusion would decrease as the level of insulin resistance increased. Method s: Adolescents (n=15, 4 females, age 15±2 yr) were studied. IR was estimated by calculating HOMA-IR (using fasting glucose and insulin), which spanned a spectrum of IR up to but excluding diabetes. Subjects underwent a magnetic resonance imaging (MRI) study visit to assess cerebral perfusion using arterial spin labeling (ASL). The CAT12 toolbox extension for SPM12 was used to process MRI data. Heart rate (HR), mean arterial pressure (MAP), and end tidal CO 2 (ETCO 2 ) were assessed. Significance was determined using linear regression and set at p≤0.05. Results: Results are mean±SD. HR (72±10 bpm, p=0.98), MAP (73±6 mmHg, p=0.67), and ETCO 2 (37±2 mmHg, p=0.91) were similar across HOMA-IR (0.5 to 3.8). Perfusion (ml/100g/min) at the amygdala (r 2 =0.33, p=0.02) and parahippocampal gyrus (r 2 =0.28, p=0.04) decreased as HOMA-IR increased. Borderline significant decreases were found for total gray matter (r 2 =0.26, p=0.051), anterior cingulate cortex (r 2 =0.26, p=0.052), and hippocampus (r 2 =0.23, p=0.07) perfusion as HOMA-IR increased. No associations were found between HOMA-IR and the following: total white matter (r 2 =0.18, p=0.11), precuneus (r 2 =0.20, p=0.10), thalamus proper (r 2 =0.14, p=0.17), and entorhinal cortex (r 2 =0.16, p=0.14) perfusion. Total gray matter (p=0.49) and white matter (p=0.73) volume had no significant relationship with HOMA-IR. HOMA-IR was not associated with any differences in regional volumes. Conclusions: Our results suggest with increasing HOMA-IR there is a significant reduction in gray matter perfusion in key brain regions associated with memory in adolescents. In contrast, structural changes were not detected, indicating functional decrements occur prior to structural deficits. These findings support our hypothesis that cerebral perfusion is associated with insulin resistance in adolescents, which may negatively impact long-term brain health. NIH R21 HD097510 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.