Complications and Comorbidities of Type 1 Diabetes

1 型糖尿病的并发症和合并症

• 批准号: 8436645
• 负责人: Janet Kathleen Snell-Bergeon
• 金额: $ 73.03万
• 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 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8436645
• 关键词: Address; Adult; Advanced Glycosylation End Products; Age; Atherosclerosis; Biological Markers; Blood Pressure; Blood Vessels; Brain natriuretic peptide; Caliber; Cardiac; Cells; Clinical Trials Design; Cohort Studies; Comorbidity; Complication; Complications of Diabetes Mellitus; Coronary Arteriosclerosis; Development; Diabetes Mellitus; Diabetic Angiopathies; Endothelial Cells; Endothelium; Event; Functional disorder; General Population; Glycosylated hemoglobin A; Guidelines; Harvest; Hyperglycemia; Hypoglycemia; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Kidney; Kidney Diseases; Knowledge; Low-Density Lipoproteins; Measurement; Measures; Michigan; Microalbuminuria; 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; follow-up; glycemic control; high risk; instrument; macrovascular disease; mortality; non-diabetic; novel; point of care; premature; prevent; prospective; protein expression; public health relevance; screening; sex

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）：与一般人群相比，目前1型糖尿病（T1D）并发症的主要挑战之一是冠状动脉疾病（CAD）的风险大幅增加。虽然更严格的血糖、血压和血脂控制降低了肾病和视网膜病变的发生率，但T1D和非糖尿病患者之间CAD风险的差距仍然存在，这无法用传统的危险因素来解释。本研究将探讨不直接影响T1D血管并发症的新因素的作用