Chromium Picolinate in the Metabolic Syndrome

描述（由申请人提供）：代谢综合征（MetSyn）是一组代谢异常，其特征为腹部肥胖、空腹血糖受损（IFG）、血脂异常和血压升高。MetSyn与2型糖尿病（T2 DM）和动脉粥样硬化性心血管疾病（ASCVD）的风险增加有关。国家胆固醇教育计划（NCEP）的最新指南包括MetSyn的新定义，并将其确定为治疗的重要靶点。使用这个新定义，估计22%的美国人以某种形式拥有MetSyn。因此，这意味着专门针对MetSyn的治疗在降低T2 DM和ASCVD的发生率方面非常重要。补充三价铬（Cr+3）已被证明可以改善一些T2 DM患者的胰岛素敏感性，但其对T2 DM高风险患者的影响尚不清楚。还有有趣的文献表明，补充Cr+3可以减轻体重和改善血脂，所有这些都是MetSyn的重要组成部分。此外，最近的体外数据表明，Cr+3也可能具有抗氧化和抗炎特性，进一步表明补充Cr+3可能有助于预防T2 DM及其并发症。因此，我们建议在一项为期4个月的双盲、随机、安慰剂对照试验中，系统评价超生理剂量的Cr+3在患有NCEP定义的MetSyn和IFG的肥胖成人中的安全性和有效性。首先，这项试验将回答每天口服1000 mcg吡啶甲酸铬（CrPic）是否可以安全地改善这一高危人群的胰岛素敏感性，通过静脉频繁采样葡萄糖耐量试验获得的几个指标进行测量。本研究还将量化补充CrPic对MetSyn中观察到的其他重要临床特征的影响，包括：血清高密度脂蛋白胆固醇（HDL-C）和空腹甘油三酯（TG）;体重/身体成分;和血压。此外，这项研究将提供关于补充CrPic对氧化应激和炎症的最新读数的影响的第一个人体数据，这些读数是T2 DM和ASCVD发展的重要中间体。最后，该研究将提供证据证明铬状态和对胰岛素敏感性的影响之间的关系，以及MetSyn人群中铬缺乏症的患病率。这项临床试验的结果将为未来的R 01资助申请提供充足的初步数据，进一步研究补充CrPic对糖尿病和冠心病预防的影响。

DESCRIPTION (provided by applicant): The metabolic syndrome (MetSyn) is a cluster of metabolic abnormalities which is characterized by abdominal obesity, impaired fasting glucose (IFG), dyslipidemia and raised blood pressure. The MetSyn has been linked to an increased risk of developing both type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). The most recent guidelines from the National Cholesterol Education Program (NCEP) include a new definition for MetSyn, and have identified it as an important target of therapy. Using this new definition, it is estimated that 22% of Americans have the MetSyn in some form. Thus, the implication is that therapies aimed specifically at the MetSyn will be very important in reducing the incidence of T2DM and ASCVD. Supplemental trivalent chromium (Cr+3) has been shown to improve insulin sensitivity in some patients with T2DM, but its effect in patients at high risk of developing T2DM is unknown. There is also intriguing literature to suggest that supplemental Cr+3 may reduce weight and improve serum lipids, all of which are important components of the MetSyn. Additionally, recent in vitro data suggests that Cr+3 may also possess antioxidant and anti-inflammatory properties, further suggesting that supplemental Cr+3 might be useful in preventing T2DM and its complications. Thus, we propose to systematically evaluate the safety and efficacy of supra-physiologic doses of Cr+3 in obese adults with NCEP-defined MetSyn and IFG in a four-month, double-blind, randomized, placebo-controlled trial. Primarily, this trial will answer whether 1000 mcg of oral chromium picolinate (CrPic) taken daily can safely improve insulin sensitivity in this high risk population as measured by several indices obtained from an intravenous frequently sampled glucose tolerance test. This study will also quantify the effects of CrPic supplementation on other important clinical features seen in MetSyn including: serum high density lipoprotein cholesterol (HDL-C) and fasting triglycerides (TG); weight/body composition; and blood pressure. Additionally, this study will provide the first human data on the effects of CrPic supplementation on state-of-the art readouts of oxidant stress and inflammation, which are important intermediates in the development of both T2DM and ASCVD. Finally, the study will provide evidence of the relationship between chromium status and effects on insulin sensitivity as well as information on the prevalence of chromium deficiency in the MetSyn population. The results from this clinical trial will provide ample preliminary data for future R01 grant submissions further investigating the effects of CrPic supplementation in diabetes and coronary heart disease prevention.