Kohnert Klaus-Dieter, Freyse Ernst-Joachim, Salzsieder Eckhard
Institute of Diabetes Gerhardt Katsch Karlsburg, Germany.
Curr Diabetes Rev. 2012 Sep;8(5):345-54. doi: 10.2174/157339912802083513.
The importance of glycaemic variability (GV) as a factor in the pathophysiology of cellular dysfunction and late diabetes complications is currently a matter of debate. However, there is mounting evidence from in vivo and in vitro studies that GV has adverse effects on the cascade of physiological processes that result in chronic β-cell dysfunctions. Glucose fluctuations more than sustained chronic hyperglycaemia can induce excessive formation of reactive oxygen (ROS) and reactive nitrogen species (RNS), ultimately leading to apoptosis related to oxidative stress. The insulin-secreting β-cells are particularly susceptible to damage imposed by oxidative stress. Evidence from experiments, using isolated pancreatic islets or β-cell lines, has linked intermittent high glucose, which mimicks GV under diabetic conditions, to significant impairment of β-cell function. Several clinical studies reported a close association between GV and β-cell dysfunction, although the deleterious effects are difficult to demonstrate. Notwithstanding, early therapeutic interventions in patients with type 1 as well as type 2 diabetes, using different strategies of optimising glycaemic control, have shown that favourable outcomes on recovery and maintenance of β-cell function correlated with reduction of GV. The purpose of the present review is to discuss the detrimental effects of GV and associations with β-cell function as well as upcoming therapeutic strategies directed towards minimising glucose excursions, improving β-cell recovery and preventing progressive β-cell loss. Measuring GV has importance for management of diabetes, because it is the only one component of the dysglycaemia that reflects the degree of dysregulation of glucose homeostasis.
血糖变异性（GV）作为细胞功能障碍和糖尿病晚期并发症病理生理学中的一个因素，其重要性目前仍存在争议。然而，体内和体外研究越来越多的证据表明，GV对导致慢性β细胞功能障碍的一系列生理过程具有不利影响。与持续性慢性高血糖相比，血糖波动更易诱导活性氧（ROS）和活性氮（RNS）过度生成，最终导致与氧化应激相关的细胞凋亡。分泌胰岛素的β细胞对氧化应激造成的损伤尤为敏感。使用分离的胰岛或β细胞系进行的实验证据表明，模拟糖尿病状态下GV的间歇性高血糖与β细胞功能的显著受损有关。尽管有害影响难以证实，但几项临床研究报告了GV与β细胞功能障碍之间存在密切关联。尽管如此，对1型和2型糖尿病患者采用不同的优化血糖控制策略进行早期治疗干预，结果显示β细胞功能恢复和维持的良好结果与GV降低相关。本综述的目的是讨论GV的有害影响及其与β细胞功能的关联，以及即将出现的旨在最小化血糖波动、改善β细胞恢复和预防β细胞进行性丢失的治疗策略。测量GV对糖尿病管理具有重要意义，因为它是血糖异常中唯一反映葡萄糖稳态失调程度的一个组成部分。
