Obesity risk in African American women is determined by a diet-by-phenotype interaction

摘要 非裔美国人(AA)女性的肥胖负担不成比例。我们公布的数据显示 导致了一种挑衅性的假设，即这种差异是有生理基础的。具体地说，AA女性是 以对葡萄糖刺激的高急性胰岛素分泌反应为特征，以及肝脏的减少 胰岛素提取，这两项共同导致餐后循环中的胰岛素浓度可以增加几倍 高于高加索(欧洲裔美国人，EA)女性。胰岛素的生脂作用 可能有利于将能量分配给脂肪组织，但代价是ATP(能量)的产生。事实上，AA 女性的能量需求比电针女性低，而且能量效率更高。高胰岛素 然而，分泌只是决定胰岛素作用的一个因素；另一个主要因素是胰岛素敏感性。 我们的数据显示，随着时间的推移，容易肥胖的AA女性的体重(脂肪)增加比那些 对胰岛素更敏感，而“肥胖抵抗”(体质偏瘦)的AA女性的胰岛素相对较低 胰岛素敏感性。我们的数据还表明，再生障碍性贫血妇女中胰岛素的生脂作用因 高血糖饮食，促进胰岛素分泌。最后，我们的数据表明，随着时间的推移，体重(脂肪) AA女性的增加是通过胰岛素敏感性和饮食血糖负荷的组合来预测的。已被占用 综上所述，这些观察表明，许多再生障碍性贫血女性由于她们的 内分泌成分，这种倾向会因高血糖饮食而加剧。一位天生的 这一假设的推论是，为了实现有意的减肥，低(与高)血糖饮食 将促进身体脂肪的更大减少，并将通过增加能量来成功地保持减肥 支出。这一推论得到了我们的初步数据的支持，这些数据表明， AA妇女在受控条件下的低血糖饮食与高血糖饮食。本文提出的项目将测试 这些假说是通过肥胖AA患者高血糖饮食与低血糖饮食的随机临床减肥试验得出的 女人。这项研究有一个有效阶段(减肥期间的控制喂养)来探索生理学 机制(能量消耗、代谢效率)和有效阶段(6个月自由生活 后续)，以检验低血糖饮食在促进减肥方面更有效的假设 维持的部分原因是改善了坚持和生活质量，以及实施饮食的简便性。这 这项研究的创新之处在于，它提出了测试一种特定的生理机制，这种机制可能是导致 肥胖；它包括疗效和效果结果；它包括数量和质量 方法；它解决了减肥和减肥维护的优化问题。这项研究是 旨在为改进减肥的临床护理方法提供必要的证据基础。

Summary African-American (AA) women are disproportionately burdened by obesity. Our published data have led to the provocative hypothesis that this disparity has physiologic underpinnings. Specifically, AA women are characterized by a high acute insulin secretory response to a glucose challenge, as well as reduced hepatic insulin extraction, which together lead to postprandial circulating insulin concentrations that can be several fold higher than those observed in Caucasian (European-American, EA) women. The lipogenic actions of insulin could favor partitioning of energy to adipose tissue at the expense of ATP (energy) production. In fact, AA women have lower energy requirements than EA women, and are more energetically efficient. High insulin secretion, however, is only one factor that determines insulin action; another major factor is insulin sensitivity. Our data have shown that over time, weight (fat) gain in obesity-prone AA women is higher in those who are more insulin sensitive, whereas “obesity-resistant” (constitutionally lean) AA women have relatively lower insulin sensitivity. Our data also suggest that the lipogenic actions of insulin in AA women are exacerbated by a high-glycemic diet, which promotes insulin secretion. Finally, our data have shown that over time weight (fat) gain in AA women is predicted by the combination of insulin sensitivity and dietary glycemic load. Taken together, these observations suggest that many AA women are predisposed to obesity by their endocrine make-up, and that this predisposition is exacerbated by a high-glycemic diet. A natural corollary of this hypothesis is that for implementation of intentional weight loss, a low- (vs high-) glycemic diet will promote greater loss of body fat, and will enable successful weight loss maintenance by increasing energy expenditure. This corollary is supported by our preliminary data that indicate a 50% greater loss of fat with low- vs high-glycemic diet under controlled conditions in AA women. The project proposed herein will test these hypotheses through a randomized clinical weight loss trial of high- vs low-glycemic diets in obese AA women. The study has both an efficacy phase (controlled feeding during weight loss) to probe physiologic mechanisms (energy expenditure, metabolic efficiency), and an effectiveness phase (6-month free-living follow-up) to test the hypothesis that the low-glycemic diet will be more effective at promoting weight loss maintenance due in part to improved adherence and quality of life, and ease of implementing the diet. This study is innovative in that it proposes to test a specific physiologic mechanism that may underlie propensity to obesity; it includes both efficacy and effectiveness outcomes; it involves both quantitative and qualitative methodology; and it tackles optimization of both weight loss and weight loss maintenance. This study is intended to provide the evidence base necessary to improve the clinical care approach to weight loss.