Ectopic adiposity in black men with high type 2 diabetes risk

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DESCRIPTION (provided by applicant): Obesity and type 2 diabetes (T2D) disproportionately affect black individuals. Generalized obesity and other established risk factors do not explain the racial disparity in T2D, and this is particularly evident among men. Emerging evidence indicates that fat accumulation in non-adipose tissues (referred to as ectopic adiposity) may be associated with T2D, independent of general obesity. Compared to white men, both obese and lean black men have less visceral and liver adiposity, while in contrast, they paradoxically have more skeletal muscle adiposity. Skeletal muscle is crucial for maintaining glucose homeostasis, and thus, skeletal muscle adiposity may be the key adipose tissue depot contributing to increased T2D risk in blacks. However, much remains to be learned about the epidemiology of skeletal muscle adiposity, particularly among high-risk black populations. Through the K01 (DK083029) and R03 (DK092348) funded pilot studies for new investigators, the applicant has begun to investigate the epidemiology of skeletal muscle adiposity and other ectopic adipose tissue depots in a well-characterized, large cohort of black men from the Tobago Health Study. This cohort offers a unique opportunity to study a black population with low levels of total adiposity, and low prevalence of other potential confounding variables, but with a high prevalence of T2D, especially among non- obese men. We are proposing to continue and expand upon our preliminary research on ectopic adiposity in this cohort. We will take advantage of our unique resource of archived computed tomography (CT) scan image files from over 1500 black men, aged 40 years and above, to analyze skeletal muscle adiposity changes over an average of nearly 7 years, and characterize the natural history of skeletal muscle adiposity changes with aging in black men, and the temporal relationship of these changes with glucose and insulin homeostasis. We will also use archived biological specimens to measure physiologic markers of potential importance for skeletal muscle adiposity, and test several compelling hypotheses about the etiology and consequences of skeletal muscle adiposity. In addition, we will obtain new CT measures of visceral, liver, abdominal muscle and pericardial adiposity, and will test for an association of abdominal skeletal muscle adiposity with measures of glucose and insulin homeostasis, and determine if these associations are independent of liver, visceral and pericardial adiposity. The proposed study will greatly advance our understanding of ectopic adiposity and its role in T2D among high risk black men.