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.

项目总结/摘要 血糖变化在优化糖尿病和血管并发症管理中的作用 已经充分证明，高葡萄糖水平导致大血管和血管内皮细胞的更快发展。 糖尿病患者的微血管并发症然而，没有一致的证据表明， 葡萄糖水平接近正常水平可以预防或减缓血管并发症，特别是在更先进的 2型糖尿病的早期症状最近的VADT、雅阁和ADVANCE试验表明， 降低血糖对血管并发症的发生率只有适度的影响。为什么血糖控制策略 专注于降低葡萄糖水平和HbA 1c的药物在降低血管生成方面没有预期的成功。 结果并不清楚。这提出了以下可能性：（1）存在超出反映血糖指标的血糖指标， 平均血糖控制，如HbA 1c，可以解释这一矛盾，（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效果， 强化治疗效果不佳的患者亚组抵消了那些确实有反应的患者。在 最近的报告表明，长期血糖变异性与心血管疾病的风险相关， 即使在调整了传统的血糖控制标志物后，也无法避免疾病（CVD）事件。重要的是，这似乎 与那些接受强化血糖控制的人最相关。这些初步调查结果支持谨慎的 检查血糖变异性的决定因素和后果。因此，在本建议中，我们建议 (a)评估和比较血糖变化的重要性，无论是短期测量的1，5-脱水葡萄糖醇 和长期的大血管和微血管并发症的发展;（B）研究是否强化 当血糖变化受到限制时，治疗有益于预防血管结局;（c）遗传 T2 D患者中与血糖变异相关的变异将解释进展为血管性糖尿病的额外风险。 与平均血糖水平相关的遗传变异之外的并发症。