GLYCEMIC CONTROL AND COMPLICATIONS IN DIABETES MELLITUS TYPE 2

2 型糖尿病的血糖控制和并发症

• 批准号: 7378142
• 负责人: RALPH A DEFRONZO
• 金额: $ 24.84万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378142
• 关键词: GLYCEMIC; CONTROL; COMPLICATIONS; DIABETES; MELLITUS

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: Type 2 diabetes mellitus is a common metabolic disorder that affects approximately 15 million Americans and is associated with considerable morbidity and mortality. Several recent studies, including the United Kingdom Prospective Diabetes Study, have shown that intensive glycemic control with insulin, sulfonylureas, or metformin all decreased microvascular complications; only metformin decreased microvascular complications in this study. However, the diabetic patients were newly diagnosed, reasonably well controlled (HbA1c ~ 7.0%), and free of complications at the time of entry. Currently, no intervention study has examined the effect of intensive glycemic control with insulin in a high risk population of type 2 diabetic patients who are poorly controlled and on oral hypoglycemic agents. This study tests the hypothesis that improved glycemic control in persons with established type 2 diabetes will reduce the incidence of macrovascular complications -- specifically it will delay the onset and progression of incidence of coronary artery and peripheral vascular disease. RESEARCH PLAN AND METHODS: The present study is a 7 year prospective, randomized, multicenter, controlled trial to determine whether intensified glycemic control is effective in preventing macrovascular complications in type 2 diabetic patients who no longer are responsive to oral agents alone. The study will be performed at 20 centers within the Veterans Administration Health Care System. Subjects are randomized into one of two arms of intensive treatment vs. standard treatment. The randomization is stratified by hospital, current insulin use, and prior microvascular disease. The goals of glycemic control are: Hemoglobin A1c levels of 8.0 - 9.0% in the standard therapy arm and hemoglobin A1c levels 6.0% in the intensive treatment arm. The treatment steps are determined by the protocol and are designed to expose both groups of patients to the same agents, but at different dosages. Both groups receive Rosiglitazone and either Glimepiride (lean) or Metformin (obese). If the hemoglobin A1c or blood glucose goals for the arm are not met, insulin is added (morning in the standard arm, evening in the intensive arm). Further steps increase dose or add other oral agents to keep patient within goals. Patients are seen every 1.5 months, and Intensive patients are called at least every two weeks. Subjects enrolled in both arms receive nutritional counseling, advice about exercise, and diabetes education. Ancillary treatment for diabetic complications is the same for both groups and follows VA and American Diabetes Association Clinical Guidelines. Management of hypertension and hyperlipidemia is standardized for both groups. Smoking cessation advice is given to both groups. All subjects will be asked to take 325 mg of Aspirin daily. The goal is to have the primary difference between the two arms of the study primarily be level of glycemic control. At follow-up visits, subjects in both study arms will be assessed for: 1. Assessments of side effects, risk factors, and treatment adherence will be assessed at each follow-up visit. Specifically, symptoms of hyperglycemia, glyucosuria, or episodes of hypoglycemia; insulin or oral agent dosage and timing; non-smoking adherence; body weight; estimations of compliance with dietary treatment regimen and self-monitoring of glycemic control; blood pressure and pulse; and examination of lower extremities (skin, pulses, ulcers). 2. Neurological examination - every 12 months. 3. Ophthalmological examination - every 12 months. 4. Blood and urine chemistries - glucose each visit - other tests yearly 5. Electrocardiogram - every 6 months 6. Assessments of intercurrent illnesses, infections, and new events - each visit 7. Quality of Life and Activity Assessment - every 12 months. 8. Complete physical examination - every 12 months. 9. Concomitant medication assessment (including use of folate, vitamin B6, vitamins C and E) - every 3 months. 10. Dietary Assessment - every visit. The primary endpoint is time to occurrence of any of the following: myocardial infarction, new or worsening congestive heart failure, stroke, invasive revascularization, amputation for ischemia, cardiovascular death. The secondary endpoints include, in addition, new or worsening angina, new transient ischemic attack, new intermittent claudication, new critical limb ischemia, and all-cause mortality.

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。目的：2型糖尿病是一种常见的代谢紊乱，影响了大约1500万美国人，并与相当高的发病率和死亡率相关。最近的几项研究，包括英国前瞻性糖尿病研究，表明胰岛素、磺脲类药物或二甲双胍强化血糖控制均可减少微血管并发症；在这项研究中，只有二甲双胍减少了微血管并发症。然而，糖尿病患者为新诊断，控制较好（HbA1c ~ 7.0%），入院时无并发症。目前，没有干预研究检查胰岛素强化血糖控制在控制不良的2型糖尿病高危人群和口服降糖药的效果。本研究验证了一个假设，即改善2型糖尿病患者的血糖控制将减少大血管并发症的发生率，特别是它将延缓冠状动脉和周围血管疾病的发病和进展。研究计划和方法：本研究是一项为期7年的前瞻性、随机、多中心、对照试验，旨在确定强化血糖控制是否能有效预防对口服药物不再有反应的2型糖尿病患者的大血管并发症。这项研究将在退伍军人管理局医疗保健系统内的20个中心进行。受试者被随机分为强化治疗和标准治疗两组。随机分组根据医院、当前胰岛素使用情况和既往微血管疾病进行分层。血糖控制的目标是：标准治疗组糖化血红蛋白水平为8.0 - 9.0%，强化治疗组糖化血红蛋白水平为6.0%。治疗步骤由方案决定，旨在使两组患者暴露于相同的药物，但剂量不同。两组均接受罗格列酮和格列美脲（瘦）或二甲双胍（肥胖）治疗。如果患者的糖化血红蛋白或血糖指标未达到，则需添加胰岛素（标准组为早上，强化组为晚上）。进一步的步骤是增加剂量或添加其他口服药物以使患者保持在目标范围内。患者每1.5个月就诊一次，重症患者至少每两周就诊一次。两组受试者均接受营养咨询、运动建议和糖尿病教育。两组糖尿病并发症的辅助治疗是相同的，并遵循VA和美国糖尿病协会临床指南。两组的高血压和高脂血症的管理都是标准化的。这两组人都得到了戒烟建议。所有受试者将被要求每天服用325毫克阿司匹林。目的是让两组研究的主要差异主要体现在血糖控制水平上。在随访中，两个研究组的受试者将被评估：1。在每次随访中评估副作用、危险因素和治疗依从性。特别是高血糖、糖尿症或低血糖发作的症状；胰岛素或口服药物的剂量和时机；不吸烟的依从性;体重;饮食治疗方案依从性评估及血糖控制自我监测；血压和脉搏；下肢检查（皮肤、脉搏、溃疡）。2. 神经系统检查——每12个月一次。3. 眼科检查-每12个月一次。4. 血液和尿液化学检查——每次检查葡萄糖——其他检查每年一次。每6个月做一次心电图。评估并发疾病，感染和新事件-每次访问7。生活质素及活动评估-每12个月。8. 每12个月进行一次全面体检。9. 伴随的药物评估（包括使用叶酸，维生素B6，维生素C和E） -每3个月。10. 饮食评估-每次访问。主要终点是发生以下任何情况的时间：心肌梗死，新发或恶化的充血性心力衰竭，中风，有创性血运重建术，因缺血而截肢，心血管死亡。此外，次要终点包括新发或恶化的心绞痛、新发短暂性脑缺血发作、新发间歇性跛行、新发危重肢体缺血和全因死亡率。