The Impacts of Adipose Tissue and the Gut Microbiome on Diabetes Risk among African-Caribbean Men

Type 2 diabetes (T2D) and its complications are increasing in prevalence and burden worldwide. Caribbean rates of T2D rival those of the United States, and mortality from T2D is exceptionally higher. The study of novel T2D risk factors, such as adipose tissue (AT) radiodensity, AT distribution, and the intestinal microbiome, yield greater insights into T2D pathophysiology and can inform targeted interventions. However, individuals of African ancestry, who have a higher burden of T2D compared to Caucasian counterparts, are underrepresented in this research. Thus, this dissertation fills the gaps by investigating associations of AT radiodensity, body composition, and the intestinal microbiome with T2D in a cohort of African Caribbean men from Tobago, Trinidad and Tobago. The first dissertation paper investigates associations between AT radiodensity in the abdomen (visceral [VAT] and subcutaneous [SAT]) and thigh (intermuscular [IMAT]) with glucose, insulin, and insulin resistance. We demonstrate that lower radiodensity in any AT (indicating greater tissue lipid accumulation) was associated with higher insulin and insulin resistance, with independent contributions from thigh IMAT. The second dissertation paper models the associations of both AT and muscle from the abdomen and thigh with T2D. We report that abdominal SAT (but not VAT) was positively associated, and thigh muscle negatively associated, with higher odds of T2D. The third dissertation paper examines associations of the intestinal microbiome with sociodemographic, lifestyle, body composition, and T2D measures. We identified sociodemographic factors as a main driver of microbial clustering, and several lifestyle and body composition measures as being differentially associated with taxonomic units, thus informing future prediction modeling of the microbiome with T2D. These findings have significant public health implications. Our results somewhat differ from those reported in predominantly Caucasian cohorts, highlighting the importance of including racial/ethnic minorities in novel risk factor research. These papers also provide important methodological work, informing how body composition analyses are performed. Finally, this research produced the first nutritional and microbiome databases in Tobago, which can aid future T2D research. Taken together, information from this dissertation can be leveraged to inform future observational and interventional studies in T2D prevention, both in the Caribbean and worldwide.