All ETDs from UAB

Advisory Committee Chair

Barbara A Gower

Advisory Committee Members

Pankaj Arora

Jose Fernandez

Kevin R Fontaine

Suzanne E Judd

Document Type

Thesis

Date of Award

2022

Degree Name by School

Doctor of Philosophy (PhD) School of Health Professions

Abstract

African American (AA) individuals are disproportionately burdened by cardiometabolic disease, including type 2 diabetes (T2D) and cardiovascular disease (CVD), and associated risk factors. The objective of this dissertation research was to investigate pathophysiological and lifestyle contributors to racial disparities in cardiometabolic disease including beta-cell dysfunction, ectopic fat, the natriuretic peptide system, and diet. These first three risk factors, beta-cell dysfunction, ectopic fat, and the natriuretic peptide system, were explored in a cross-sectional study of young AA and European American (EA) adults. The fourth risk factor, diet, was explored in a large, national cohort of black and white adults. First, we investigated associations between the proinsulin-to-C-peptide ratio (PI:CP), an index of proinsulin secretion, and indices of beta-cell response and function. We observed AA individuals to have higher PI:CP than EA individuals. We also observed PI:CP to be inversely associated with first-phase beta-cell function (DId) and insulin sensitivity in AA individuals. Next, we investigated disparities in renal sinus fat (RSF), an ectopic fat depot associated with cardiometabolic disease. We found RSF to be inversely associated with diastolic blood pressure in AA individuals. Additionally, RSF was positively associated with age, sex, and total body fat in AA individuals. In EA individuals, RSF was positively associated with insulin sensitivity and inversely associated with intraabdominal and perimuscular adipose tissue (PMAT). Thirdly, we explored associations between N-terminal pro-atrial natriuretic iv peptide (NT-proANP), insulin, and adipose tissue. We found NT-proANP to be lower in AA individuals and inversely associated with post-challenge insulin. In EA individuals, NT-proANP was inversely associated with fasting insulin and HOMA-IR. Thigh subcutaneous adipose tissue and PMAT were positively associated with NT-proANP in EA individuals; however, this association was attenuated upon adjustment for age and sex. Finally, we found black race to be the characteristic with highest adherence to the Southern dietary pattern, a dietary pattern associated with cardiometabolic disease. Findings from these four aims point towards physiological differences among AA and EA individuals. These physiological differences, in combination with diet, likely contribute to the greater cardiometabolic disease prevalence in AA individuals.

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