DIET-INDUCED HYPERINSULINEMIA IN OBESE HYPERTENSION

原发性高血压构成了一种异质性疾病， 特别是在肥胖人群中，这一点是公认的。 高胰岛素血症与胰岛素抵抗关系的研究进展 对这种复杂疾病的病因学研究是这项研究的主要目标 求婚。但这一目标取决于DISTINCT的先前定义 亚群对降压效应的敏感性 减肥。我们的假设是高胰岛素血症和胰岛素 阻力是“体重”发展的主要因素 由肥胖引起的“敏感”高血压。 这项提案将调查胰岛素与 肥胖患者体重减轻后阻力与高血压的关系 计划(NIH ROL HL 31989)，其目的是评估 对减肥的抗升压作用敏感。分析 这些受试者的血压变化 失重率为10%呈双峰分布，均值为 (加或减SD)舒张压下降23+或 -3毫米汞柱和3正负5毫米汞。建议进行的研究 旨在证明胰岛素敏感性的变化 根据同时血糖和胰岛素计算的指数(SI) 根据Bergman的最小模型，数据是一个预测因子 血压对体重减轻的反应。为了确立这一点， 每个患者都将在体重减轻后进行研究；患者的子集 30%的累犯率和第二次体重减轻也将被研究。 协变量将包括Na+/K+排泄、儿茶酚胺 排泄，血浆肾素活性，血浆心钠素， 体重指数(Wt/HT2)、年龄和性别。 同时实验将在费舍尔和扎克进行 饲喂高脂肪或高碳水化合物饲料的FA/FA肥胖大鼠 描绘一个类似的动物模型。血液动力学 这些动物的特征将通过使用 心输出量和局部血流速度的测量 不同的组织。胰岛素增强血管功能的假说 对急性或慢性容量扩张的自动调节 将会受到考验。自动调节(对血管阻力的反应) 将在基础胰岛素状态下和在两个水平上测量 高胰岛素/正常血糖葡萄糖钳夹。 因此，在肥胖动物和人类受试者身上进行的平行实验 将被用来检验一个机械论假说 肥胖中的高胰岛素血症与原发性高血压有关。

That primary hypertension constitutes a heterogeneous disorder, particularly in the obese population, is well recognized. Elucidation of the role of hyperinsulinemia and insulin resistance in the etiology of this complex disorder is a primary goal of this proposal. But this goal hinges upon the prior definition of distinct subgroups with respect to sensitivity to the anti-pressor effects of weight loss. Our hypothesis is that hyperinsulinemia and insulin resistance are major factors in the development of "weight sensitive" hypertension due to obesity. This proposal will investigate the relationship between insulin resistance and hypertension in obese patients in a weight loss program (NIH ROL HL 31989), an aim of which is to evaluate sensitivity to the anti-pressor effects of weight loss. Analysis of the change in blood pressure achieved in those subjects whose weight loss was 10% reveals a bimodal distribution with mean (plus or minus SD) decline in diastolic blood pressure of 23 plus or minus 3 mmHg and 3 plus or minus 5 mmHg. The proposed study is designed to demonstrate that the change in Insulin Sensitivity Index (SI) calculated from simultaneous blood glucose and insulin data according to the Minimal Model of Bergman, is a predictor of the response of blood pressure to weight loss. To establish this, each patient will be studied after weight loss; a subset of patients with 30% recidivism and a second weight loss will also be studied. Covariates will include Na+/K+ excretion, catecholamine excretion, plasma renin activity, plasma atrial naturetic factor, body mass index (wt/ht2), age and sex. Concurrent experiments will be conducted in Fischer and Zucker fa/fa obese rats fed high fat or high carbohydrate diets in order to delineate an analogous animal model. The hemodynamic characteristics of these animals will be evaluated using measurements of cardiac output and regional blood flow rates in different tissues. The hypothesis that insulin potentiates vascular autoregulation in response to acute or chronic volume expansion will be tested. Autoregulation (response in vascular resistance) will be measured in the basal insulin state, and at two levels of hyperinsulinemic/euglycemic glucose clamps. Thus, parallel experiments in obese animals and human subjects will be used to test a mechanistic hypothesis about the role of hyperinsulinemia in obesity as it relates to primary hypertension.