Mentored Patient-Oriented Research Career Development Aw

提案(改编自申请人的摘要)：提案的目标 研究是为了确定胰岛素抵抗所起的作用 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)肥胖者的减肥能力；以及 2)非糖尿病个体和2型患者患冠心病的风险 糖尿病。这些问题很重要，因为肥胖症在中国的流行 美国已经达到了流行的程度，并正在推动 2型糖尿病和冠心病。而肥胖、胰岛素抵抗和糖尿病 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/或增加的趋势中起着重要作用 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 以下是：1)比较胰岛素抵抗和胰岛素敏感 非糖尿病、超重的个人，关于他们失去的能力 低卡路里饮食的体重。减肥前后冠心病危险因素分析 也将进行评估，以确定胰岛素抵抗的程度 与非糖尿病超重个体的冠心病风险增加有关，因为 以及胰岛素抵抗的差异对 减肥对新陈代谢的好处。2)确定体重减轻及其 相关的新陈代谢益处随以下物质的相对量而变化 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，与饮食构成的关系 循环胰岛素浓度的变化将在以下方面进行分析 体重减轻和冠心病危险因素。3)量化和比较 与体重相关的血糖控制和冠心病危险因素的改善 肥胖型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(噻唑二酮)。 使用这些药物控制血浆胰岛素浓度将 提供一种评估循环胰岛素影响的机制 在所描述的结果测量上的浓度。

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.