Complications and Comorbidities of Type 1 Diabetes

1 型糖尿病的并发症和合并症

• 批准号: 8846654
• 负责人: Janet Kathleen Snell-Bergeon
• 金额: $ 73.57万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8846654
• 关键词: Address; Adult; Advanced Glycosylation End Products; Age; Atherosclerosis; Biological Markers; Blood Pressure; Blood Vessels; Brain natriuretic peptide; Caliber; Cardiac; Cells; Cohort Studies; Comorbidity; Complication; Complications of Diabetes Mellitus; Coronary Arteriosclerosis; Development; Diabetes Mellitus; Endothelial Cells; Endothelium; Event; General Population; Glycosylated hemoglobin A; Guidelines; Harvest; Health; Hyperglycemia; Hypoglycemia; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Kidney; Kidney Diseases; Knowledge; Low-Density Lipoproteins; Measurement; Measures; Michigan; Microalbuminuria; Microvascular Dysfunction; Monitor; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Outcome Study; Oxidative Stress; Patients; Peripheral Nervous System Diseases; Persons; Phenotype; Population; Prevalence; Preventive; Radiation; Renal function; Retinal; Retinal Diseases; Risk; Risk Factors; Risk Marker; Role; Study Subject; Subgroup; Treatment Efficacy; Troponin; adjudication; aged; arterial stiffness; autonomic neuropathy; blood lipid; cohort; coronary artery calcification; disorder risk; endothelial dysfunction; follow-up; glycemic control; high risk; instrument; macrovascular disease; mortality; non-diabetic; novel; point of care; premature; prevent; prospective; protein expression; screening; sex; trial design

DESCRIPTION (provided by applicant): One of the key challenges in type 1 diabetes (T1D) complications today is the vastly increased risk of coronary artery disease (CAD), compared to the general population. While more intensive glycemic, blood pressure and lipid control has decreased the rates of nephropathy and retinopathy, the gap in CAD risk between T1D and non-diabetic persons has persisted, unexplained by conventional risk factors. This proposed study will examine the role of novel factors in vascular complications of T1D that are not directly addressed by current preventive guidelines: insulin resistance, AGEs, oxidative stress, and endothelial dysfunction. Anticipated results will inform the design of trials to prevent premature CAD and further delay microvascular complications in patients with T1D. The Coronary Artery Calcification in Type 1 Diabetes (CACTI) study has followed 1416 adults (652 with T1D, 764 non-diabetic controls) aged 19-56 years at the baseline examination in 2000-2002, and re-examined after 3 and 6 years. The unique features of this cohort include: population-representativeness of the T1D and non- diabetic (Non-DM) subjects, large size, and availability of prospectively defined cardio-renal phenotypes. We are proposing a 12-year follow-up examination of this cohort. Coronary artery calcification (CAC), the main study outcome, is an excellent marker of CAD risk in the general population. This proposed study will significantly expand our knowledge concerning CAC associations with macro- and micro-vascular complications of T1D, and will help to develop alternative biomarkers that do not involve radiation and can be administered at point of care to identify those T1D patients at high risk. Specific Aim 1: Evaluate development and progression of subclinical coronary atherosclerosis over 12 years in these well characterized cohorts of T1D patients and Non-DM controls to: i) Determine if there is evidence for continued divergence of progression of subclinical atherosclerosis in these groups; ii) Evaluate novel risk factors; and iii) Explore additional non-invasive measurements of CAD. iv) Continue annual ascertainment of CAD events (including revascularization) and mortality in all study subjects. Specific Aim 2: In all subjects, continue prospective assessment of renal function, and: i) Determine whether renal complications independently predict CAC progression, and whether T1D patients without renal complications have increased risk of CAC ii) Assess additional, novel microvascular complications to estimate the global burden of microvascular complications and their association with CAC; iii) Evaluate novel risk markers (insulin resistance, AGEs, glycemic control and variability) as factors common to all complications. Specific Aim 3: Examine endothelium-specific mechanisms of micro and macrovascular complications in a subgroup of T1D and Non-DM subjects identified from the study cohorts with complications vs. without.

描述（由申请人提供）：与普通人群相比，当今1型糖尿病（T1 D）并发症的关键挑战之一是冠状动脉疾病（CAD）的风险大幅增加。虽然更强化的血糖、血压和血脂控制降低了肾病和视网膜病变的发生率，但T1 D和非糖尿病患者之间CAD风险的差距仍然存在，无法用传统风险因素解释。这项拟议的研究将探讨新的因素在T1 D血管并发症中的作用，这些因素不是直接的。 目前的预防指南解决了以下问题：胰岛素抵抗、AGEs、氧化应激和内皮功能障碍。预期结果将为试验设计提供信息，以预防T1 D患者的过早CAD并进一步延迟微血管并发症。 1型糖尿病患者冠状动脉钙化（CACTI）研究在2000-2002年的基线检查中随访了1416名年龄在19-56岁的成人（652名T1 D患者，764名非糖尿病对照），并在3年和6年后重新检查。该队列的独特特征包括：T1 D和非糖尿病（非DM）受试者的人群代表性、大样本量和前瞻性定义的心肾表型的可用性。我们建议对该队列进行12年的随访检查。 主要研究结果是冠状动脉钙化（CAC），它是一般人群中CAD风险的一个极好标志物。这项拟议的研究将显著扩大我们对CAC与T1 D大血管和微血管并发症相关性的了解，并将有助于开发不涉及辐射的替代生物标志物，并可在护理点进行管理，以识别高风险的T1 D患者。具体目标1：在这些充分表征的T1 D患者和非DM对照队列中评价12年内亚临床冠状动脉粥样硬化的发展和进展，以：i）确定这些组中是否存在亚临床动脉粥样硬化进展持续差异的证据; ii）评价新的风险因素; iii）探索CAD的其他无创测量方法。iv）继续每年确定所有研究受试者的CAD事件（包括血运重建）和死亡率。具体目标二：在所有受试者中，继续对肾功能进行前瞻性评估，以及：i）确定肾脏并发症是否独立预测CAC进展，以及无肾脏并发症的T1 D患者是否具有CAC风险增加; ii）评估额外的新型微血管并发症，以估计微血管并发症的总体负担及其与CAC的相关性; iii）评估新的风险标志物（胰岛素抵抗、AGEs、血糖控制和变异性）作为所有并发症的共同因素。具体目标3：在从有并发症与无并发症的研究队列中确定的T1 D和非DM受试者亚组中检查微血管和大血管并发症的内皮特异性机制。