ATENOLOL EXPOSURE AS RISK FOR ADVERSE METABOLIC RESPONSES TO BETA BLOCKERS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 心血管疾病--心血管疾病是美国人死亡的主要原因，高血压是重要的心血管危险因素。它也是中风、心脏病发作、肾功能衰竭和心力衰竭的危险因素。β-受体阻滞剂和利尿剂是治疗高血压的推荐一线药物。来自各种研究的数据表明，高血压患者患糖尿病的风险与降压药物策略有关。2型糖尿病约占新发糖尿病病例的90%，并发生在60%的高血压患者中。 数十年来，β-受体阻滞剂和利尿剂一直被用于治疗高血压，并已被证明可以降低高血压患者的心血管发病率和死亡率。反对主要使用β-受体阻滞剂的理由之一是担心对血脂和胰岛素敏感性的不利代谢影响。另一个副作用是β-受体阻滞剂导致体重增加的倾向。肥胖症现在被公认为是总死亡率的重要预测指标。体重增加是绝大多数高血压患者和几乎所有2型糖尿病高血压患者的临床问题。 虽然，各种报告表明，低剂量的利尿剂对血脂和胰岛素敏感性没有负面影响；但没有关于β-受体阻滞剂的研究报告。通过这项研究，我们将确定代谢效应的发生与β-受体阻滞剂全身血浆浓度之间的浓度反应关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular disease-CVD is the leading cause of mortality in the United States of America and hypertension is an important cardiovascular risk factor. It is also a risk factor for stroke, heart attack, renal failure and heart failure. Beta-blockers along with diuretics are among the recommended first-line agents for the treatment of hypertension. Data from various studies indicate that the risk of developing diabetes in hypertensive patients is related to the antihypertensive drug strategy. Type 2 diabetes comprises ~ 90% of new cases of diabetes and occurs in 60% of hypertensive patients. Beta-blockers and diuretics have been used for the treatment of hypertension for decades and have been shown to decrease cardiovascular morbidity and mortality rates in patients with essential hypertension. One of the arguments against the primary use of beta-blockers has been the concern about adverse metabolic effects on the lipid profile and on insulin sensitivity. Another side effect is the propensity of beta-blockers to cause weight gain. Obesity is now well recognized as an important predictor of overall mortality. Increased body weight is a clinical problem in the vast majority of hypertensive patients and almost all type 2 diabetic hypertensive patients. Although, various reports indicate low doses of diuretics to be free from negative effects on the lipid profile and insulin sensitivity; no such studies are reported for the beta-blockers. Through this study we will determine concentration response relationship between the occurrence of metabolic effects and beta-blocker systemic plasma concentrations.