低血糖(hypoglycemia) 一直是糖尿病患者血糖控制的一大障礙，讓醫療從業人員對於積極血糖管控顯得投鼠忌器。一些大型的臨床試驗已經證實積極的血糖控制可以降低小血管疾病(microvascular disease)，但對於是否能有效降低大血管疾病(macrovasculardisease) 的證據則還不充分。最近一些大型的臨床試驗，針對病史較久的糖尿病患者，發現積極的血糖控制對於心血管疾病，可能是沒有好處，甚至是有害的。於是治療過程的低血糖，到底是不是元
兇，受到廣泛的討論。低血糖會造成交感腎上腺的活化(sympathoadrenal activation)、心臟再極化異常(abnormal cardiac repolarization)、血栓形成增加(increased
thrombogenesis)、發炎反應(inflammation)、內皮細胞功能異常(endothelial dysfunction)，以及心臟自主神經功能失調(impaired cardiac autonomic function)。從大型臨床試驗分析(ACCORD 及ADVANCE)，低血糖雖無法解釋積極血糖控制組較多的死亡率或抵銷了積極血糖管控的好處，卻發現不管是對照組或積極血糖管控組，發生嚴重低血糖的患者，大血管疾病、小血管疾病、任何原因造成的死亡及非心血管疾病的發生率，相較未發生嚴重低血糖的患者，均呈有意義的升高。故雖然無法確定低血糖與心血管疾病的因果關係，但低血糖對於糖尿病程長的患者，的確是一個代表預後不好的標記。

Hypoglycemia is always a barrier to control blood sugar in patients with diabetes. It makes physicians to have scruples in intensive glycemic control. Some large clinical trials have proven that intensive glycemic control could lower the rate of microvascular disease. Howevr, it is still controversial for macrovascular disease. Recent large clinical trials looking at intensive glycemic control have shown no benefit or potential harm in patients with a longer duration of diabetes. Thus, hypoglycemia as a risk factor for cardiovascular events is a topic of much dabate.Hypoglycemia causes sympathoadrenal activation, abnormal cardiac repolarization, increased thrombogenesis,inflammation, endothelial dysfunction, and impaired cardiac autonomic function. Despite hypoglycemia was not a likely explanation for the excess mortality in the ACCORD trial and no survival benefit in the ADVANCE trial, it was true both in standard glucose control and intensive glucose control that hypoglycemia was clearly associated with increased macrovascular, microvascular, and death from both cardiovascular and noncardiovascular
causes. In conclusion, hypoglycemia is really a marker of vulnerability to a wide range of adverse clinical outcomes. But current evidences cannot make sure that hypoglycemia has a direct cause of these outcomes.