A Role for Glycemic Variation in Optimizing Management of Diabetes and Vascular Complications

血糖变化在优化糖尿病和血管并发症管理中的作用

• 批准号: 10040813
• 负责人: Peter D Reaven
• 金额: $ 12.28万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10040813
• 关键词: Algorithms; Blood Vessels; Cardiovascular system; Characteristics; Clinical; Clinical Trials; Data; Databases; Development; Diabetes Mellitus; Equilibrium; Event; Genetic; Genetic Markers; Genetic Risk; Glucose; Glycosylated hemoglobin A; Goals; Incidence; Individual; Lead; Life Style; Long-Term Effects; Measures; Microvascular Dysfunction; Modeling; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Patient risk; Patients; Play; Population; Principal Investigator; Reporting; Risk; Risk Factors; Risk stratification; Role; Sampling; Subgroup; Testing; Time; Variant; Visit; base; blood glucose regulation; cardiovascular disorder risk; cohort; comorbidity; database of Genotypes and Phenotypes; diabetes management; genetic variant; genome-wide; glycemic control; improved; individualized medicine; innovation; machine learning algorithm; macrovascular disease; patient subsets; predictive modeling; prevent; random forest; secondary analysis; standard care; success; treatment arm; treatment effect

PROJECT SUMMARY/ABSTRACT A role for glycemic variation in optimizing management of diabetes and vascular complications It is well demonstrated that high glucose levels lead to more rapid development of macrovascular and microvascular complications in people with diabetes. However, there is less consistent evidence that lowering glucose levels to near normal levels prevent or slows vascular complications, particularly in more advanced stages of type 2 diabetes. The recent VADT, ACCORD, and ADVANCE trials demonstrated that intensive efforts to lower glucose had only modest effects on the rate of vascular complications. Why glycemic control strategies that focused on reduction of glucose levels and HbA1c did not have the anticipated success in reducing vascular outcomes is not clear. This has raised the possibility that (1) there are glycemic metrics beyond those that reflect average glucose control, such as HbA1c, that can explain this paradox, and (2) there exists heterogeneous treatment effects of intensive glycemic therapy for macrovascular and microvascular complications, with subgroups of patients who do less well with intensive treatment counter-balancing those that do respond. In recent reports we have demonstrated long-term glycemic variability was associated with risk of cardiovascular disease (CVD) events, even after adjusting for traditional markers of glycemic control. Importantly, this appeared most relevant to those receiving intensive glycemic control. These preliminary findings support careful examination of determinants and consequences of glycemic variability. In this proposal, we therefore propose to (a) evaluate and compare the importance of glycemic variation, both short-term measured by 1,5-anhydroglucitol and long-term in the development of macro and microvascular complications; (b) to study whether intensive treatment is beneficial in preventing vascular outcomes when glycemic variation is constrained; (c) genetic variants associated with glycemic variation in T2D patients will explain additional risk in progression to vascular complications beyond the genetic variants associated with mean glycemic levels.

项目摘要/摘要 血糖变异在优化糖尿病治疗和血管并发症治疗中的作用 很好地证明，高葡萄糖水平会导致大血管和 糖尿病患者的微血管并发症。但是，有较少的证据表明降低 葡萄糖水平达到接近正常水平，预防或减慢血管并发症，尤其是在更先进的情况下 2型糖尿病的阶段。最近的VADT，ACCORD和ADVARDEAR表现表明，密集型努力 对于较低的葡萄糖，对血管并发症率的影响只有适中的影响。为什么血糖控制策略 重点是降低葡萄糖水平和HBA1C，在减少血管方面没有预期的成功 结果尚不清楚。这增加了（1）除反映的血糖指标之外的可能性 可以解释这种悖论的平均葡萄糖控制，例如HBA1C，并且（2）存在异质性 强化血糖治疗对大血管和微血管并发症的治疗作用， 在强化治疗中表现不佳的患者的亚组反应反应的患者。在 最近的报道我们已经证明长期血糖变异性与心血管风险有关 疾病（CVD）事件，即使在调整了血糖控制的传统标记后也是如此。重要的是，这出现了 与接受密集血糖控制的人最相关。这些初步发现支持谨慎 检查决定因素和血糖变异性的后果。因此，在此提案中，我们建议 （a）评估和比较血糖变异的重要性，这两者都是由1,5- 2烷基葡萄醇测量的短期 长期发展宏观和微血管并发症； （b）研究是否密集 当血糖差异受到限制时，治疗对预防血管结局是有益的。 （c）遗传 T2D患者与血糖变异相关的变异将解释进展为血管的额外风险 超出与平均血糖水平相关的遗传变异的并发症。