Abstract 45: Elevated Long-Term Triglyceride-Glucose Index Variability From Childhood is Linked to Poorer Midlife Cognitive Function: The Bogalusa Heart Study

Abstract

Background: Insulin resistance has been linked to a higher risk of cardiovascular events and cognitive impairment in older adults. Recently, an elevated triglyceride-glucose (TyG) index, a noninvasive marker of insulin resistance, has been linked to a greater risk of cardiovascular disease. Whether long-term TyG index variability from childhood to midlife impacts midlife cognitive function (CF) is unclear. Hypothesis: We hypothesized that elevated TyG index variability from childhood to midlife is associated with poorer midlife CF. Aim: We aimed to identify the impact of elevated TyG index variability from childhood to midlife on midlife CF. Methods: We studied 1,100 midlife Bogalusa Heart Study participants (age at enrollment: mean 9.5 years +/- standard deviation(SD) 3.5 years; age at midlife: 48.1 +/- 5.2 years; 60.3% women(663 of 1100), 34% Black(374 of 1100)) with ≥ 3 lipid and glucose measurements across follow-up. Participants with Type 2 diabetes mellitus were excluded. TyG index levels were calculated as ln [(serum fasting triglyceride in mg/dL x serum fasting glucose in mg/dL)/2]. TyG index measures of each individual were fitted into random-effects models stratified by race and sex, and individual growth curves were obtained. Visit-to visit TyG index variability from childhood to midlife was calculated by the deviation from age-predicted values (DEV) and residual SD (RSD) from these models. Midlife CF was measured from 10 neuropsychological (NP) tests, which were categorized into 3 distinct NP profiles (optimal, average, and mixed-low) using cluster analysis. Associations between TyG index variability and NP profiles were analyzed using multinomial logistic regression models, adjusting for education status and the mean of TyG index levels from childhood to midlife. DEV and RSD were standardized to z-scores according to race and sex before regression analysis. Interactions according to race and sex were performed. Results: Every 1 SD increase in DEV increased the odds of having a mixed-low CF by 48.9% (95% CI 1.201, 1.847) and an average CF by 22.9% (95% CI 1.046, 1.443) compared to optimal CF, after adjusting for education status and mean TyG levels. Every 1 SD increase in RSD increased the odds of having a mixed-low CF by 51% (95% CI 1.217, 1.873) and an average CF by 25.4% (95% CI 1.068, 1.472) compared to optimal CF, adjusting for education status and mean TyG levels. Neither race nor sex modified the effects of DEV nor RSD on CF. Conclusions: Greater long-term TyG index variability was linked with poorer midlife CF. Further studies are needed to elucidate the brain effects of higher long-term variability in insulin resistance from childhood to midlife.