Identifying Risk for Diabetes and Heart Disease in Women: A Study of African-American, African and White Federal Employees and Contractors

联邦妇女研究是一项积极的临床方案，旨在招募360名在华盛顿特区大都市区工作的联邦雇员和承包商。109名妇女(非洲裔美国人占56%，非洲移民占17%，白人占31%)接受了筛查(年龄在24-62岁之间)。30%的女性患有贫血，这是筛查女性未被登记的最常见原因。在登记的妇女中，在教育程度、糖尿病家族史和体力活动等关键社会经济和人口风险因素方面，这三个群体在种族/族裔方面非常匹配。然而，我们已经在39%的女性(42%的非裔美国人，13%的非洲移民和29%的白人)中发现了糖尿病前期。因此，这一队列反映了糖尿病和心脏病的高危妇女，以及(A)测试现有筛查测试的有效性和(B)按种族/族裔了解心脏代谢性疾病的病理生理进展的优秀群体。由于目前的心脏代谢筛查试验以甘油三酯和空腹血糖浓度为中心，我们采用了两种方法来检查这些危险因素。 甘油三酯与胰岛素抵抗和高胰岛素血症的关系 这项研究将按种族/民族和起源大陆比较甘油三酯浓度与心脏代谢关键风险因素的关系，特别是饮食、体力活动、胰岛素抵抗(和高胰岛素血症)和肝脏脂肪含量。到目前为止，我们发现与我们的假设一致，空腹甘油三酯浓度在非洲移民中最低，在白人女性中最高(AI：5312vs.AA：6733vs.WW：8334 mg/dL，P&lt；0.01)，非洲裔美国女性的胰岛素敏感性指数(AI：3.11.7vs.AA：2.51.6vs.WW：3.42.2mU/L-1min-1，P=0.2)和对葡萄糖的急性胰岛素反应更强(AI：895528 vs.AA：959790 vs.WW：561429 mU/L，P=0.07)。对肝脏脂肪含量与胰岛素抵抗的关系的分析正在进行中。在总脂肪百分比方面，没有种族/民族的差异，但体内脂肪分布的差异是明显的，特别是内脏脂肪组织(VAT)体积(VAT；AI：4836vs.AA：8642vs.WW：11854 cm~3，P=0.001)。 为了进一步确定胰岛素分泌、胰岛素清除和进餐肠道因素对高胰岛素血症种族/民族差异的影响，我们比较了胰岛素对口服、静脉和进餐葡萄糖负荷的反应。初步研究结果表明，早期餐后血糖反应存在种族差异。非洲裔女性的餐后胰岛素浓度反而更高，但血糖反应却更低，我们正在进一步探索胰岛素浓度对高胰岛素血症的定量贡献。我们计划继续招募，并期待有一个扩展的数据集，对我们的主要结果变量、甘油三酯浓度和关键调整因素(饮食组成、体力活动、胰岛素敏感性指数和肝脏脂肪)进行中期分析。 这些分析应该提供特定人群的证据，阐明重要的病理生理途径，并最终导致加强筛查和诊断指南，从而有可能将世界各地与糖尿病有关的健康差距缩小到最低限度。

The Federal Women Study is an active clinical protocol aimed at recruiting 360 federal employees and contractors working in the Washington DC metropolitan area. One hundred and nine women (56% African-American, 17% African immigrant and 31% white) have been screened (age 449, range 24-62 years). Thirty percent of women had anemia and this was the most common reason that screened women were not enrolled. Among the enrolled women, the three groups are well matched by race/ethnicity for key socio-economic and demographic risk factors such as educational attainment, family history of diabetes and physical activity. Yet, we have already identified pre-diabetes in 39% of women (42% African-American, 13% African immigrant and 29% white). Therefore, this cohort reflects women who are at high risk for diabetes and heart disease and an excellent group in which to (a) test the efficacy of existing screening tests and (b) understand the pathophysiological progression of cardiometabolic disease by race/ethnicity. As current cardiometabolic screening tests are centered on triglyceride and fasting glucose concentrations, we have employed two approaches to examine these risk factors. The Relationship of Triglycerides with Insulin Resistance and Hyperinsulinemia This study will compare by race/ethnicty and continent of origin, the relationship of triglyceride concentration to key cardiometabolic risk factors, specifically diet, physical activity, insulin resistance (and hyperinsulinemia) and hepatic fat content. We have found so far that consistent with our hypothesis, fasting triglyceride concentrations are lowest in African immigrant and highest in white women (AI: 5312 vs. AA: 6733 vs. WW: 8334 mg/dL, P<0.01) with a trend for lower insulin sensitivity index (AI: 3.11.7 vs. AA: 2.51.6 vs. WW: 3.42.2 mU/L-1min-1, P=0.20) and greater acute insulin response to glucose (AI: 895528 vs. AA: 959790 vs. WW: 561429 mU/L, P=0.07) in African-American women. Analysis of the relationship of hepatic fat content with insulin resistance is underway. In regard to total percent fat there were no differences by race/ethnicity but differences in body fat distribution were clear, specifically visceral adipose tissue (VAT) volume (VAT; AI: 4836 vs. AA: 8642 vs. WW: 11854 cm3, P=0.001). To further characterize the contribution of insulin secretion, insulin clearance and prandial gut factors to race/ethnic differences in hyperinsulinemia, we are comparing insulin response to oral, intravenous and prandial glucose loads. Preliminary findings suggest racial differences in early postprandial glucose response. African descent women have paradoxically greater postprandial insulin concentrations but lower glucose response and we are exploring further the quantitative contribution of incretin concentrations to hyperinsulinemia. We plan to continue recruitment and look forward to an expanded dataset with interim analyses of our primary outcome variable, triglyceride concentration, with key modifying factors (diet composition, physical activity, insulin sensitivity indices and hepatic fat). These analyses should provide population-specific evidence which elucidate important pathophysiological pathways and ultimately lead to enhanced screening and diagnostic guidelines which have the potential to minimize diabetes related health disparities worldwide.