Diabetes is a prevalent chronic disease associated with elevated risks of cardiovascular disease (CVD) and premature mortality. In 2021, 38.4 million individuals in the United States (US), accounting for 11.6% of the population, had diabetes, with 95% of them having type 2 diabetes (T2D). T2D is a multifaceted metabolic disorder characterized by both impaired insulin action and secretion. Projections indicate that the number of people with T2D in the US will rise to 48 million by 2050. Meanwhile, racial disparities of T2D in the US have been well documented and are persistent over time. National Diabetes Statistics Report indicated that, in 2017–2018, the age-adjusted incidence of diagnosed T2D was highest among Hispanic (9.7 per 1000 persons), followed by non-Hispanic Black (8.2 per 1000 persons), non-Hispanic Asian (7.4 per 1000 persons) and non-Hispanic White (5.0 per 1000 persons) populations. These groups also experience more severe complications and higher mortality rates related to T2D. Thus, it is crucial to find determinants of T2D contributing to the racial disparities.Various risk factors contribute to the development of T2D and many of them are modifiable such as socioeconomic status (SES), behaviors (e.g., exercise), and obesity. Factors SES such as education and income, which impacts downstream behaviors and obesity, may be the upstream cause of developing T2D and its disparities among racial and ethnic groups. Meanwhile, associations of personal and neighborhood SES with T2D are deeply intertwined. A composite measurement encompassing personal and neighborhood, social and environmental conditions, which is social determinants of health (SDOH), is essential for comprehensively understanding how interconnected social conditions relate to T2D risk. Meanwhile, racial and ethnic minorities may experience worse SDOH than Whites due to systemic racism. However, up to now, no studies have yet examined the associations between SDOH integrating several domains and T2D. In addition, it is well-known that exercise could reduce T2D risk. Obesity, particularly the accumulation of visceral fat, has been hypothesized to be a primary risk factor for T2D. Meanwhile, compared to Whites, some racial and ethnic minorities (e.g., Hispanics, Blacks and Asians) have lower levels of exercise, and some minorities (e.g., Hispanics and South Asians) have higher levels of visceral fat, which may explain the racial disparities in T2D. Additionally, there are sex differences in visceral fat. Nonetheless, no studies have examined to what extent the association of race and ethnicity with T2D is mediated by exercise, or visceral fat. Thus, the dissertation investigated SDOH integrating several domains to determine associations between comprehensively assessed social disadvantages and T2D as well as if the associations varied by race and ethnicity (Objective 1). In addition, the dissertation examined whether and to what extent the association of race and ethnicity with T2D can be explained by exercise (Objective 2), and examined to what extent the association of race and ethnicity with T2D can be explained by visceral fat within sex subgroups (Objective 3).
To address these objectives, this dissertation used the data from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective longitudinal cohort study including multiple racial and ethnic groups. We assessed SDOH comprehensively from several domains and applied modern casual mediation analysis to examine mediation effects of exercise and visceral fat. We found that disadvantaged SDOH was associated with increased T2D risk in a dose-response manner in all participants, and the associations existed in Whites and Hispanics when stratified by race and ethnicity. In addition, exercise accounted for one-tenth of racial differences in T2D comparing Hispanics or Chinese to Whites. Furthermore, visceral fat explained one-fifth of the racial disparities in T2D comparing Hispanic females to White females. As T2D is largely preventable, these findings highlight modifiable pathways that could inform future interventions for higher T2D risks among racial and ethnic minorities and promoting health equity. Specifically, prioritizing resources for populations with social disadvantages may reduce the T2D burdens, particularly among at-risk Hispanics to decrease T2D disparities. Additionally, interventions on increasing exercise are needed for each racial and ethnic group, and especially important among Hispanics and Chinese to lower their higher T2D risks. Furthermore, understanding the role of visceral fat in contributing to racial disparities in T2D among Hispanic females enhances our comprehension of the biological factor at play.
