Ectopic adiposity in black men with high type 2 diabetes risk

描述（由申请人提供）：肥胖和2型糖尿病（T2D）不成比例地影响黑人个体。广泛性肥胖和其他已确定的危险因素不能解释 T2D的种族差异，这在男性中尤为明显。新出现的证据表明，非脂肪组织中的脂肪蓄积（称为异位肥胖）可能与T2D相关，与一般肥胖无关。与白色男性相比，无论是肥胖的还是精瘦的黑人男性，内脏和肝脏的肥胖程度都较低，而相反，他们却有更多的骨骼肌肥胖。骨骼肌对于维持葡萄糖稳态至关重要，因此，骨骼肌肥胖可能是导致黑人T2D风险增加的关键脂肪组织储存库。然而，关于骨骼肌肥胖症的流行病学，特别是在高危黑人人群中，仍有许多问题有待研究。通过K01（DK083029）和R03（DK092348）资助的新研究者初步研究，申请人已开始在托巴哥健康研究的一个特征明确的大型黑人男性队列中研究骨骼肌肥胖和其他异位脂肪组织贮库的流行病学。该队列提供了一个独特的机会来研究黑人人群，该人群的总肥胖水平较低，其他潜在混杂变量的患病率较低，但T2D的患病率较高，尤其是在非肥胖男性中。我们建议继续并扩大我们对这一队列异位肥胖的初步研究。我们将利用我们独特的存档计算机断层扫描（CT）图像文件资源，这些文件来自1500多名40岁及以上的黑人男性，分析平均近7年的骨骼肌肥胖变化，并描述黑人男性骨骼肌肥胖随年龄增长而变化的自然史，以及这些变化与葡萄糖和胰岛素稳态的时间关系。我们还将使用存档的生物标本来测量对骨骼肌肥胖具有潜在重要性的生理标志物，并测试关于骨骼肌肥胖的病因和后果的几个令人信服的假设。此外，我们将获得内脏、肝脏、腹肌和心包脂肪的新CT测量值，并将测试腹部骨骼肌脂肪与葡萄糖和胰岛素稳态测量值的相关性，并确定这些相关性是否独立于肝脏、内脏和心包脂肪。这项研究将极大地促进我们对异位肥胖及其在高危黑人男性T2D中的作用的理解。

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.