Heavy Metals, Obesity and Cardiovascular Risk

描述(由申请人提供)： 重金属是一组非均相的高活性物质，可能 作为生理过程的基本辅因子和/或有毒元素。 特别是，铬与肥胖、糖尿病和体重有关。 损失。其他重金属与以下一些后果有关 肥胖，包括高血压、高脂血症和心血管疾病。 前瞻性研究，一项大规模的强化的随机对照试验 生活方式干预对肥胖2型糖尿病患者体重减轻的影响 糖尿病，为解决铬的影响提供了一个极好的机会 关于减肥和糖尿病控制，以及评估其他 重金属对减肥的生理后果。我们提出了一个 前瞻试验内的辅助前瞻性观察性研究 收集所有参与者(n=5,000)在基线和 为期一年的访问，并分析脚趾甲的随机子集(1150 基线趾甲和480个1年访问趾甲)，以了解它们的重金属含量 使用仪器中子活化分析。脚趾甲提供了一种 重金属暴露量的时间积分测量，而仪器中子 活化分析提供了大约50种重金属在 脚趾甲样本，包括铬。这些信息将使我们能够评估 基线趾甲铬浓度与体重减轻的关系，AS 以及重金属之间的相互作用和重金属的有益影响 减肥。拟议的研究可能会为我们提供对 减肥干预效果的决定因素。事实上，你的眼神 先期试验，由于其规模，可能是为数不多的研究之一，在这些研究中 关系可以可靠地衡量。此外，附属研究将会 允许建立一个脚趾甲样本库，以供将来使用 重金属相关性的病例队列或嵌套病例对照研究 具有前瞻性终点，特别是心肌梗死和心血管疾病 死亡。

DESCRIPTION (provided by applicant): Heavy metals are a heterogeneous group of highly reactive substances, which may act as essential cofactors for physiologic processes and/or as toxic elements. Chromium, in particular, has been associated with obesity, diabetes, and weight loss. Other heavy metals have been associated with some of the consequences of obesity, including hypertension, hyperlipidemia, and cardiovascular disease. The Look AHEAD Study, a large randomized controlled trial of intensive lifestyle intervention for weight loss in obese patients with Type 2 diabetes mellitus, provides an excellent opportunity to address the impact of chromium on weight loss and diabetes control, as well as to assess the impact of other heavy metals on the physiologic consequences of weight loss. We propose an ancillary prospective observational study within the Look AHEAD trial to collect toenail clippings from all participants (n = 5,000) at baseline and at the 1-year visit, and to analyze a random subset of the toenails (1,150 baseline toenails and 480 1-year visit toenails) for their heavy metal content using instrumental neutron activation analysis. Toenails provide a time-integrated measure of heavy metal exposure, while instrumental neutron activation analysis provides the concentrations of about 50 heavy metals in the toenail samples, including chromium. This information will allow us to evaluate the relationship of baseline toenail chromium concentrations to weight loss, as well as the interaction between heavy metals and the beneficial effects of weight loss. The proposed study may provide, valuable insight into the determinants of the efficacy of weight loss interventions. In fact, the Look AHEAD trial, because of its size, may be one of the few studies in which these relationships can be measured reliably. In addition, the ancillary study will permit the setup of a specimen bank of toenails to be used in future case-cohort or nested case-control studies of the association of heavy metals with Look AHEAD endpoints, especially myocardial infarction and cardiovascular death.