Is glycemic control a quinidine‐like intervention? 控制血糖与使用奎尼丁治疗一样吗？
摘要
Six years ago three randomized controlled clinical trials directed at understanding the effect of glycemic control in prevention of cardiovascular disease (CVD) were published, with the counterintuitive finding that, despite extensive evidence from epidemiologic studies that individuals with higher glucose levels are more likely to have CVD and its complications, these largely effective glycemic interventions showed no overall evidence of reduction in CVD.1-3 The question is therefore frequently asked, “Does glycemic control benefit diabetic patients?” Of course, when phrased in this fashion one realizes that it is unlikely that any given intervention will have the same effect in all people with a given illness, and that perhaps by returning to these landmark trials we can, with hindsight, understand what may be a reasonable explanation of their apparent failure. An interesting example of the complexity of determining the circumstances under which an intervention may be considered beneficial is the example of quinidine given by Williams,4 who pointed out that its use in patients with atrial fibrillation was found to be associated with sudden death, leading to it being “virtually banned as a drug”, although this appears only to be the case in patients with heart failure, whose mortality is increased fivefold by the agent, whereas the (much larger) group with normal cardiac function actually has a 30% reduction in mortality when treated with quinidine. Might we then hypothesize that aggressive glycemic treatment may, under certain circumstances, and to a considerably lesser degree, increase mortality in a vulnerable “late” subgroup of diabetic patients, whereas it is likely to reduce CVD in responsive “early” disease? Indeed, there is some evidence that such a pattern occurs from epidemiologic analysis of “U-shaped” curves of the relationship between HbA1c levels and mortality among patients with diabetes.5, 6 Such a pattern was seen in the control arm of the Action t