THE EFFECTS OF OLMESARTAN MEDOXOMIL, LOSARTAN POTASSIUM, AND ATENOLOL ON INSU

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。胰岛素抵抗现在被公认为心血管风险的贡献者，并被认为与代谢综合征的发展有关，代谢综合征是心血管危险因素的聚集性。因此，以高血压为靶点的药物如何影响胰岛素抵抗是人们感兴趣的。硫氮化物、利尿剂和β-肾上腺素能拮抗剂对胰岛素抵抗的有害作用早已被认识到。已发现钙通道阻滞剂总体上是中性的，血管紧张素转换酶抑制剂(ACEI)可能会改善胰岛素抵抗。最近在心血管流行病学研究中发现ACEI和血管紧张素受体阻滞剂(ARB)都能降低2型糖尿病的发病率，这表明ACEI对胰岛素敏感性的有益影响可能与人群水平有关，也表明这种益处可能延伸到ARB。ARBS是一类最新的抗高血压药物，ARBS对胰岛素敏感性的影响在很大程度上尚不确定。这是一项开放标签、分层、随机、三臂平行分组、多中心研究。在为期4周的安慰剂试入期以评估受试者的研究依从性之后，60名超重或肥胖(BMI 25-39 kg/m2)、高血压(JNC VI标准)的受试者将被随机分为以下三个治疗组之一：“OMesartan medoxomil(一种新的ARB，最近获得FDA批准)”Losartan Key(一种已知对胰岛素敏感性有影响的ARB，阳性对照)“Atenolol(一种β肾上腺素能拮抗剂，阴性对照)，将在安慰剂试入期结束和12周治疗后使用黄金标准的高胰岛素正血糖钳夹程序评估胰岛素敏感性。治疗前后稳态糖代谢速率的变化将是统计分析的主要终点。血压和血脂参数也将作为次要终点进行评估和分析。我们计划为这项研究在当地招募6名受试者。

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. Insulin resistance is now well accepted as a contributor to cardiovascular risk, and is felt to be causally associated with development of the metabolic syndrome, a clustering of cardiovascular risk factors. It is therefore of interest how pharmacologic agents which target hypertension affect insulin resistance. Deleterious effects of thiazides diuretics and beta-adrenergic antagonists on insulin resistance have been long recognized. Calcium channel blockers have been found to be neutral overall and angiotensin-converting enzyme inhibitors (ACEI) likely improve insulin resistance. ACEI and angiotensin receptor blockers (ARBs) have both been recently found to reduce the incidence of type 2 diabetes mellitus in cardiovascular epidemiologic studies, suggesting that beneficial effects on insulin sensitivity of ACEI may be relevant at the population level, and also suggesting that this benefit may extend to ARBs. ARBs are the newest class of antihypertensive agents, and the effects of ARBs on insulin sensitivity are largely undetermined. This is an open-label, stratified, randomized, 3-arm parallel-group, multi-center study. Following a 4-week, placebo run-in period to assess subjects for study compliance, 60 overweight or obese (BMI 25-39 kg/m2), hypertensive (JNC VI criteria) subjects will be randomized to one of the following three treatment groups: " Omesartan medoxomil (a new ARB, recently FDA approved) " Losartan potassium (an established ARB with known effects on insulin sensitivity, positive control) " Atenolol (a beta-adrenergic antagonist, negative control) Insulin sensitivity will be assessed using the gold standard hyperinsulinemic euglycemic clamp procedures at the end of the placebo run-in period and following 12 weeks' therapy. The change in glucose disposal rate at steady state before and after therapy will be the primary endpoint for statistical analysis. Blood pressure and blood lipid parameters will also be assessed and analyzed as secondary endpoints. We plan to recruit 6 subjects locally for this study.