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

总结 非裔美国人（AA）妇女不成比例地承受着肥胖的负担。我们公布的数据显示， 导致了一个挑衅性的假设，即这种差异有生理基础。具体来说，AA女性 其特征在于对葡萄糖激发的高急性胰岛素分泌反应，以及降低的肝脏胰岛素分泌。 胰岛素提取，它们一起导致餐后循环胰岛素浓度可以是 高于在高加索人（欧洲-美国，EA）女性中观察到的。胰岛素的脂肪生成作用 可能有利于以ATP（能量）产生为代价将能量分配给脂肪组织。事实上，AA 女性比EA女性的能量需求更低，并且能量效率更高。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。 我们的数据表明，随着时间的推移，肥胖倾向的AA女性的体重（脂肪）增加高于那些 更胰岛素敏感，而“肥胖抵抗”（体质瘦）AA妇女有相对较低的 胰岛素敏感性我们的数据还表明，胰岛素在AA女性中的脂肪生成作用因以下因素而加剧： 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妇女的增重是通过胰岛素敏感性和饮食血糖负荷的组合来预测的。采取 总之，这些观察结果表明，许多AA妇女易患肥胖症， 内分泌组成，这种倾向是加剧了高血糖饮食。自然 这一假设的一个推论是，为了实施有意的减肥，低血糖饮食（对高血糖饮食） 将促进更大的损失身体脂肪，并将使成功的减肥维持增加能量 支出这个推论得到了我们初步数据的支持，这些数据表明， AA女性在受控条件下的低血糖与高血糖饮食。本文提出的项目将测试 这些假设通过一项随机临床减肥试验，在肥胖AA患者中进行高血糖与低血糖饮食的比较， 妇女该研究有一个有效性阶段（减肥期间控制喂养），以探索生理 机制（能量消耗，代谢效率）和有效性阶段（6个月自由生活 随访）以检验低血糖饮食在促进减肥方面更有效的假设 部分由于改善的依从性和生活质量，以及易于实施饮食，这 这项研究的创新之处在于，它提出测试一种特定的生理机制，这种机制可能是 肥胖;它包括疗效和有效性结果;它涉及定量和定性 方法;它解决了减肥和减肥维持的优化。本研究 旨在为改善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.