Understanding the Impact of Early Life Factors on Cardiometabolic Risk throughout the Life Course in a Large and Diverse Cohort of Adolescents and Young Adults - ABSTRACT Cardiometabolic conditions — such as hypertension, prediabetes, type 2 diabetes mellitus (T2D), dyslipidemia, and metabolic dysfunction-associated fatty liver disease (MAFLD) — are among the leading causes of morbidity and mortality among US adults but are now severely affecting younger generations. Cardiometabolic conditions that emerge among adolescents and young adults (AYA) often have a more aggressive clinical course and lead to greater complications than do adult-onset ones, making identification of high-risk populations and targeted early prevention efforts for AYA critical, particularly given persistent racial and ethnic disparities across the life course. Adolescence and young adulthood are vulnerable developmental windows, in which emerging health risks may have lifelong implications for cardiovascular diseases. However, little is known about the epidemiology of cardiometabolic outcomes among AYA populations because existing studies in AYA are extremely limited due to a lack of population-based studies with diverse samples beyond Black and Latinx populations, small sample sizes, cross-sectional designs, and lack of objective measures of cardiometabolic outcomes beyond BMI. In addition, there is also pressing interest in identifying upstream risk factors, particularly early life factors, because human metabolic and endocrine systems are programmed early in life. Our long-term goal is to better understand the epidemiology of cardiometabolic outcomes among AYA, identifying high-risk groups and risk factors to inform early detection and design upstream intervention strategies to mitigate health disparities. To fill extant knowledge gaps and inform future prevention strategies, we will conduct a large longitudinal cohort study based on a diverse population of over 2.5 million AYA members (aged 12 to 26; 8% Black, 26% Latinx, 19% Asian, 1% Native Hawaiian/Pacific Islander, 0.5% Native American) at Kaiser Permanente Northern California (KPNC), an integrated health care system with membership representative of the source population. We will use electronic health record data to link diagnosis, laboratory, and other sociodemographic and clinical data to describe sex- and race/ethnicity-specific incidence and temporal trends of cardiometabolic outcomes among AYA, by sex, age group, race/ethnicity, and BMI categories (Aim 1). We will also investigate how childhood and adolescent BMI trajectories influence cardiometabolic outcomes (Aim 2), knowledge that is lacking among AYA populations. Finally, using data from a sub-cohort that was born at KPNC, we will identify prenatal and early factors associated with the cardiometabolic risks in AYA by sex and race/ethnicity (Aim 3). Results will inform early targeted interventions aimed at lowering cardiometabolic risks among high-risk groups, with the potential to reduce health disparities throughout the life course. In addition, the timing of the proposed study positions us advantageously with a comprehensive dataset covering pre-, during-, and post-pandemic periods. This unique temporal framework allows for an examination of the impact of the pandemic on cardiometabolic risks among AYAs.
