EFF BASAL/PREMEAL INS STRAT (DETEMIR/ASPART) TO IMP INS SECRETION/ACTION IN T2D

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：检查使用诺和诺德新胰岛素制剂的最佳胰岛素治疗，以确定其是否逆转葡萄糖毒性（或“糖脂毒性”）。 研究计划：将对30例未控制的T2 DM患者进行研究。 初次筛选访视后，所有受试者将入住综合临床研究中心（GCRC），为期2天半。 每例受试者将在三种情况下入院：1）治疗前; 2）步骤1（地特单药治疗后x12周）; 3）步骤2（地特+门冬胰岛素治疗后x12周）。 此后，30例患者中的20例（通过计算机生成的过程随机选择）将门冬胰岛素添加到治疗中，而另外10例患者将继续单独使用地特胰岛素。 将重复上述拟定的门诊和住院患者评价。 方法：简而言之，研究设计包括导入基线评价后的两步方法：第1步：为期3个月的地特胰岛素（诺和平）强化治疗，旨在通过这种独特的胰岛素制剂实现最佳血糖控制。 随后将进行与基线时相同的重复测量。 第二步：添加餐前门冬胰岛素（Novolog）3个月，以检查餐后血糖波动正常化的额外获益。 受试者将接受肝脏和肌肉MRS扫描。

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. OBJECTIVE: Examine optimal insulin therapy with the new insulin formulations from Novo Nordisk to determine if it reverses glucotoxicity (or "glucolipotoxicity"). RESEARCH PLAN: Thirty (30) patients with uncontrolled T2DM will be studied. After the initial screening visit all subjects will be admitted to the General Clinical Research Center (GCRC) for 2 1/2 days. Each subject will be admitted on three occasions: 1) pre-treatment; 2) Step 1 (after detemir alone x 12 weeks); and 3) Step 2 (after detemir plus aspart x 12 weeks). Following this, insulin aspart will be added to the treatment in 20 of the 30 patients (randomly chosen by a computer generated process) while the other 10 will be continued on insulin detemir alone. The outpatient and inpatient evaluations proposed above will be repeated. METHODS: In brief, the study design includes a two-step approach after the run-in baseline evaluations: Step 1: a three-month intensive insulin detemir (Levemir) treatment aimed at the best glycemic control possible with this unique insulin formulation. This will be followed by repeat measurements identical to those obtained at baseline. Step 2: addition of pre-meal insulin aspart (Novolog) for three months to examine the additional benefit of normalizing postprandial glucose excursions. Subjects will receive liver and muscle MRS scans.