Chromium Picolinate in the Metabolic Syndrome

吡啶甲酸铬在代谢综合征中的作用

• 批准号: 6675190
• 负责人: PHILIPPE O SZAPARY
• 金额: $ 19.81万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6675190
• 关键词: atherosclerosis; blood pressure; body composition; body weight; cholesterol; chromium; clinical research; clinical trials; dietary supplements; glucose metabolism; high density lipoproteins; human subject; human therapy evaluation; inflammation; insulin sensitivity /resistance; leptin; metabolic syndrome; metabolism disorder chemotherapy; noninsulin dependent diabetes mellitus; nutrition related tag; obesity; oxidative stress; pancreatic islet function; patient oriented research; triglycerides

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.

描述(申请人提供)：代谢综合征(MetSyn)是一组以腹部肥胖、空腹血糖受损(IFG)、血脂异常和血压升高为特征的代谢异常。MetSyn被认为与患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)的最新指南包括对MetSyn的新定义，并将其确定为重要的治疗目标。使用这个新的定义，估计有22%的美国人有某种形式的MetSyn。因此，这意味着针对MetSyn的治疗在减少T2 DM和ASCVD的发生率方面将非常重要。补充三价铬(Cr3+)已被证明可以改善一些T2 DM患者的胰岛素敏感性，但对T2 DM高危患者的效果尚不清楚。也有耐人寻味的文献表明，补充铬+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，铬+3还可能具有抗氧化和抗炎特性，进一步表明补充铬+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四个月的双盲、随机、安慰剂对照试验中，系统地评估使用NCEP定义的MetSyn和IFG的肥胖成年人服用超生理剂量的铬+3的安全性和有效性。首先，这项试验将回答每日服用1000微克的口服吡啶甲酸铬(CrPic)是否可以安全地改善这一高危人群的胰岛素敏感性，这是通过静脉频繁采样葡萄糖耐量试验获得的几项指数来衡量的。这项研究还将量化补充CrPic对MetSyn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；以及血压。此外，这项研究将首次提供补充CrPic对氧化应激和炎症的最新读数的影响的人类数据，这是T2 DM和ASCVD发展的重要中间产物。最后，这项研究将提供铬状况与胰岛素敏感性影响之间的关系的证据，以及关于MetSyn人群中铬缺乏症流行率的信息。这项临床试验的结果将为未来的R01拨款申请提供充足的初步数据，进一步研究CrPic补充剂在糖尿病和冠心病预防中的效果。