Mentored Patient-Oriented Research Career Development Aw

提案（改编自申请人的摘要）：提案的目标 研究的目的是确定对胰岛素介导的 葡萄糖处置（胰岛素抵抗）和循环胰岛素浓度 作为影响因素：1）肥胖个体减肥的能力;以及 2)非糖尿病个体和2型糖尿病患者的CHD风险 糖尿病 这些问题是重要的，因为肥胖的流行率在 美国已达到流行病的程度，并有助于增加 2型糖尿病与冠心病 虽然肥胖、胰岛素抵抗和糖尿病是 高度相关，尚不清楚胰岛素抵抗和代偿性 高胰岛素血症在体重增加和/或 无法减肥。 高胰岛素血症在冠心病中的作用也是 不清楚 在这方面，拟议研究的具体目标如下： 如下：1）比较胰岛素抵抗与胰岛素敏感 非糖尿病、超重的个体， 低热量饮食的体重。 减肥前后冠心病危险因素分析 也将被评估以确定胰岛素抵抗的程度， 与非糖尿病超重个体CHD风险增加相关， 以及胰岛素抵抗的差异对 减肥的代谢益处。 2)为了确定体重减轻及其 相关的代谢益处作为相对量的函数而变化， 低热量饮食中的膳食脂肪和碳水化合物。 因为高碳水化合物 饮食增加胰岛素分泌，饮食组成之间的关系 将分析循环胰岛素浓度的变化， 体重减轻和冠心病危险因素。 3)为了量化和比较 改善血糖控制和与体重相关的CHD危险因素 肥胖2型糖尿病患者在接受以下治疗时的损失：a）胰岛素 促分泌剂（磺酰脲）;或B）胰岛素增敏剂（噻唑烷二酮）。 用这些药物操纵血浆胰岛素浓度将 提供一种机制，通过该机制评估循环胰岛素的影响 浓度对所描述的结果测量的影响。

PROPOSAL (Adapted from the applicant's abstract): The goal of the proposed research is to define the roles played by resistance to insulin-mediated glucose disposal (insulin resistance) and circulating insulin concentrations as factors affecting: 1) the ability of obese individuals to lose weight; and 2) risk for CHD in both non-diabetic individuals and patients with Type 2 diabetes. These issues are important, as the prevalence of obesity in the U.S. has reached epidemic proportions, and is contributing to an increase in Type 2 diabetes and CHD. While obesity, insulin resistance, and diabetes are highly associated, it is not clear whether insulin resistance and compensatory hyperinsulinemia play important roles in the tendency to gain weight and/or inability to lose weight. The role of hyperinsulinemia in CHD is also unclear. In this regard, the specific aims of the proposed research are as follows: 1) to compare insulin resistant versus insulin sensitive nondiabetic, overweight individuals with respect to their ability to lose weight on a low calorie diet. CHD risk factors before and after weight loss will also be assessed to determine the degree to which insulin resistance is associated with increased CHD risk in non-diabetic overweight individuals, as well as the impact that differences in insulin resistance have on the metabolic benefits of weight loss. 2) To determine if weight loss and its associated metabolic benefits vary as a function of the relative amounts of dietary fat and carbohydrate in hypocaloric diets. Because high carbohydrate diets increase insulin secretion, the relationship between dietary composition and change in circulating insulin concentrations will be analyzed with respect to both weight loss and CHD risk factors. 3) To quantify and compare the improvement in glycemic control and CHD risk factors associated with weight loss in obese Type 2 diabetics, while being treated with: a) an insulin secretagogue (sulfonylurea); or b) an insulin sensitizer (thiazolidenedione). Manipulation of plasma insulin concentrations with these medications will provide a mechanism by which to evaluate the impact of circulating insulin concentrations on the described outcome measurements.