Ectopic adiposity in black men with high type 2 diabetes risk

患有 2 型糖尿病高风险的黑人男性异位肥胖

• 批准号: 8418160
• 负责人: IVA MILJKOVIC
• 金额: $ 49.59万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8418160
• 关键词: Abdomen; Abdominal Muscles; Address; Adipocytes; Adipose tissue; Affect; African American; Aging; Archives; Biological; Biological Markers; Choristoma; Confounding Factors (Epidemiology); Data; Development; Economic Burden; Elderly; Epidemiology; Etiology; Evolution; Fatty Acids; Fatty acid glycerol esters; Funding; Funding Mechanisms; Glucose; Glucose Intolerance; Health; High Prevalence; Homeostasis; Image; Individual; Infiltration; Inflammation; Inflammation Mediators; Insulin; Insulin Resistance; Interleukin-6; Learning; Leptin; Liver; Low Prevalence; Measures; Metabolic; Monocyte Chemoattractant Protein-1; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Pericardial body location; Phenotype; Physiological; Pilot Projects; Population; Prevalence; Research; Research Personnel; Resources; Risk Factors; Role; Scanning; Serum; Skeletal Muscle; Specimen; Testing; Time; Tissues; Tobago; Universities; Visceral; X-Ray Computed Tomography; adiponectin; age related; aged; attenuation; base; blood glucose regulation; cohort; cost efficient; diabetes risk; epidemiologic data; fasting glucose; fatty acid oxidation; fatty acid transport; high risk; high risk men; human FABP4 protein; innovation; insight; macrophage; men; novel; older men; population based; programs; public health relevance; racial and ethnic disparities; subcutaneous

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.

描述（由申请人提供）：肥胖和 2 型糖尿病 (T2D) 对黑人的影响尤为严重。全身性肥胖和其他既定危险因素并不能解释 T2D 存在种族差异，这在男性中尤其明显。新出现的证据表明，非脂肪组织中的脂肪积累（称为异位肥胖）可能与 T2D 相关，与一般性肥胖无关。与白人男性相比，肥胖和瘦的黑人男性的内脏和肝脏肥胖程度都较低，而相反，他们的骨骼肌肥胖程度却更高。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库。然而，关于骨骼肌肥胖的流行病学，特别是在高危黑人群体中，还有很多东西有待了解。通过 K01 (DK083029) 和 R03 (DK092348) 资助的新研究人员试点研究，申请人已开始在来自多巴哥的一大群特征明确的黑人中调查骨骼肌肥胖和其他异位脂肪组织库的流行病学健康研究。该队列提供了一个独特的机会来研究总体肥胖水平较低、其他潜在混杂变量患病率较低、但 T2D 患病率较高的黑人群体，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中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) 扫描图像文件资源，这些图像文件来自 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，并描述骨骼肌肥胖的自然史。黑人男性骨骼肌肥胖随着年龄的增长而变化，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，并测试有关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、腹部肌肉和心包肥胖的新 CT 测量结果，并将测试腹部骨骼肌肥胖与葡萄糖和胰岛素稳态测量的关联，并确定这些关联是否独立于肝脏、内脏脂肪和心包肥胖。拟议的研究将极大地增进我们对异位肥胖及其在高风险黑人男性 T2D 中的作用的理解。