COMBINED GLUCOTROL XL & ACARBOSE THERAPY IN TYPE II DM

本研究的目的是评估单独使用Glucotrol XL和阿卡波糖联合治疗无法达到足够血糖控制的II型糖尿病患者的益处。治疗的比较将包括评估空腹血糖、餐后血糖漂移、低血糖的发生率和频率、游离胰岛素、血脂和总体代谢控制。这是一项随机、双盲、平行对照试验，涉及26例2型糖尿病患者，他们在最大剂量的市售磺脲治疗后血糖升高。患者将接受筛查性实验室评估（包括CBC与差异、UA、OP16、对混合膳食反应的刺激c肽、脂蛋白谱、总胰岛素、HBA1c、EKG、空腹血糖和育龄女性的β HCG）和简短的访谈，以确定他们是否有资格参加研究。符合条件的患者将进行第2次访问，届时将进行病史和体格检查，并指导患者摄入60%的碳水化合物饮食。届时，尚未接受降糖药治疗的患者将改用降糖药。在6周的领先期后，患者必须在最大剂量的Glucotrol XL （20mg/dl）和60%的碳水化合物饮食下空腹血糖达到140mg/dl，才能进入研究。下一次访问（访问3）将包括进入杜克大学医学中心的普通临床研究中心（GCRC），在此期间将进行以下实验室测试：空腹血糖、HBA1c、c肽、总胰岛素、餐后1小时胰岛素和血糖水平、餐后2小时胰岛素和血糖水平以及脂蛋白谱。在入院期间，患者将被随机分配到两个治疗组中的一个。一种治疗将包括4个月的葡萄糖XL和安慰剂治疗。另一种治疗包括4个月的葡萄糖XL联合阿卡波糖治疗。阿卡波糖的初始剂量为25毫克/天，2周后增加到50毫克/天，如果需要，再增加2周后增加到100毫克/天。我们的终点将是空腹血糖低于120 mg/dl或最大剂量阿卡波糖。入院后大约2个月，患者将作为门诊患者返回第4次就诊。这次访问的目的是评估血糖控制水平和监测药物毒性。评估将包括家庭血糖监测和以下实验室检查：LFT和HbA1c。大约在就诊4 2个月后，患者将再次入院，重复第一次入院的实验室评估。这项研究仍在进行中，结果尚未公布。意义：2型糖尿病是一种以胰岛素抵抗和相对胰岛素缺乏为特征的综合征。虽然一些患者可以单独使用口服降糖药来控制和达到血糖，但其他患者需要胰岛素（通常是大剂量）。纠正空腹高血糖是一个主要问题，因为如果不改善空腹血糖，通常不可能纠正随后的每日高血糖。然而，在II型糖尿病患者中使用胰岛素治疗与几个问题相关，包括不变的体重增加和动脉粥样硬化的促进。因此，需要开发其他形式的治疗，以尽量减少这类患者的胰岛素使用。

The purpose of this study is to evaluate the benefits of combined Glucotrol XL and acarbose therapy in patients with type II diabetes mellitus who cannot achieve adequate glycemic control with Glucotrol alone. The comparison of treatments will include evaluation of fasting plasma glucose, post-prandial glucose excursions, incidence and frequency of hypoglycemia, free insulin, lipids, and overall metabolic control. This is a randomized, double-blinded, parallel controlled trial involving 26 patients with type II diabetes mellitus who are hyperglycemic on the maximum dose of a commercially-available sulfonylurea. Patients will undergo screening laboratory evaluations (including CBC with differential, UA, OP16, stimulated C-peptide in response to a mixed meal, lipoprotein profile, total insulin, HBA1c, EKG, fasting plasma glucose, and Beta HCG for females of reproductive age) and a brief interview to determine if they qualify for study participation. Patients who qualify will proceed to visit 2 at which time a history and physical examination will be conducted and the patients will be instructed in a 60% carbohydrate diet. At that time, patients will be switched to Glucotrol XL who are not already receiving it. Following a lead in period of 6 weeks, patients must have a fasting plasma glucose >140mg/dl on the maximum dose of Glucotrol XL (20mg/dl) and a 60% carbohydrate diet in order to enter the study. The next visit (visit 3) will consist of an admission to the General Clinical Research Center (GCRC) at Duke University Medical Center at which time the following laboratory tests will be performed: fasting plasma glucose, HBA1c, C-peptide, total insulin, 1 hr post prandial insulin and glucose levels, 2 hr post prandial insulin and glucose levels, and lipoprotein profile. During this admission, patients will be randomized to one of two treatment arms. One treatment will consists of therapy with Glucotrol XL and placebo for 4 months. The other treatment consists of 4 months of Glucotrol XL combined with acarbose therapy. The initial dose of acarbose will be 25 mg tid, increasing to 50mg tid after 2 weeks and, if necessary, to 100 mg tid after an additional 2 weeks. Our end point will be a fasting plasma glucose under 120 mg/dl or maximum dose acarbose. Approximately 2 months following the admission, patients will return for visit 4 as an outpatient. The purpose of this visit is to assess the level of glucose control and to monitor for drug toxicity. Assessment will include examination of home blood glucose monitoring and the following labs: LFT's and HbA1c. Approximately 2 months after visit 4, patients will be readmitted to repeat the laboratory evaluations of the first admission. The study is ongoing, and results are not available to date. SIGNIFICANCE: Type II diabetes mellitus is a syndrome characterized by resistance to insulin and relative insulin deficiency. While some patients can be managed and euglycemia achieved using oral hypoglycemic agents alone, others require insulin (frequently in substantial doses). Correction of fasting hyperglycemia is a main concern, since it is often impossible to correct subsequent daily hyperglycemia without improving the fasting blood glucose. However, the use of insulin therapy in patients with type II diabetes is associated with several problems, including invariable weight gain and facilitation of atherogenesis. It is therefore desirable to develop other forms of therapy which might minimize insulin use in this patient population.