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

项目摘要/摘要 血糖变化在优化糖尿病和血管并发症管理中的作用 大量研究表明，高血糖水平会导致大血管和血管病变的快速发展。 糖尿病患者的微血管并发症。然而，有不太一致的证据表明，降低 血糖水平接近正常水平可预防或减缓血管并发症，尤其是在较晚期的患者 2型糖尿病的分期。最近的VADT、ACCORD和ADVANCE试验表明，密集的努力 降糖对血管并发症的发生率影响不大。为什么选择血糖控制策略 这项研究的重点是降低血糖水平，而糖化血红蛋白并没有在减少血管方面取得预期的成功 结果尚不清楚。这增加了这样一种可能性：(1)除了那些反映血糖的指标之外，还有其他的血糖指标 平均血糖控制，如糖化血红蛋白，可以解释这一悖论；(2)存在异质性 强化降糖治疗大血管和微血管并发症的疗效观察 在强化治疗中表现不佳的患者亚组，抵消了那些确实有反应的患者。在……里面 最近的报告表明，长期血糖变异性与心血管疾病的风险有关 疾病(CVD)事件，即使在对血糖控制的传统标志物进行调整后也是如此。重要的是，这一点似乎 与那些接受强化血糖控制的人最相关。这些初步发现支持谨慎行事 检查血糖变异性的决定因素和后果。因此，在这项建议中，我们建议 (A)评估和比较血糖变化的重要性，这两种变化都是用1，5-脱水葡萄糖醇短期测量的 和长期发展的宏微血管并发症；(B)研究是否加强 当血糖变化受到限制时，治疗有益于预防血管结果；(C)遗传 与T2D患者血糖变化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。

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.