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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。胰岛素抵抗现在被广泛认为是心血管风险的一个因素，并且被认为与代谢综合征的发展有因果关系，代谢综合征是心血管风险因素的聚集。因此，针对高血压的药物如何影响胰岛素抵抗是一个有趣的问题。噻嗪类利尿剂和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。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（angiotensin receptor blockers, ARBs）均可降低2型糖尿病的发病率，这表明ACEI对胰岛素敏感性的有益作用可能与人群水平相关，并且这种益处可能延伸至arb。arb是一类最新的降压药，其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、三组平行、多中心的研究。在为期4周的安慰剂磨合期评估受试者的研究依从性后，60名超重或肥胖（BMI 25-39 kg/m2），高血压（JNC VI标准）受试者将被随机分配到以下三个治疗组之一：“奥美沙坦美多索米（一种新的ARB，最近获得FDA批准）”“氯沙坦钾（一种已知对胰岛素敏感性有影响的ARB，阳性对照）”“阿替洛尔（一种β -肾上腺素能拮抗剂，阴性对照）”胰岛素敏感性将在安慰剂磨合期结束和12周治疗后使用金标准高胰岛素正糖钳夹程序进行评估。治疗前后稳态葡萄糖处理速率的变化将作为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.