George Institute for International Health, University of Sydney, Sydney, Australia.
N Engl J Med. 2010 Oct 7;363(15):1410-8. doi: 10.1056/NEJMoa1003795.
Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention. We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes.
We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes, using Cox proportional-hazards models with adjustment for covariates measured at baseline and after randomization.
During a median follow-up period of 5 years, 231 patients (2.1%) had at least one severe hypoglycemic episode; 150 had been assigned to intensive glucose control (2.7% of the 5571 patients in that group), and 81 had been assigned to standard glucose control (1.5% of the 5569 patients in that group). The median times from the onset of severe hypoglycemia to the first major macrovascular event, the first major microvascular event, and death were 1.56 years (interquartile range, 0.84 to 2.41), 0.99 years (interquartile range, 0.40 to 2.17), and 1.05 years (interquartile range, 0.34 to 2.41), respectively. During follow-up, severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events (hazard ratio, 2.88; 95% confidence interval [CI], 2.01 to 4.12), major microvascular events (hazard ratio, 1.81; 95% CI, 1.19 to 2.74), death from a cardiovascular cause (hazard ratio, 2.68; 95% CI, 1.72 to 4.19), and death from any cause (hazard ratio, 2.69; 95% CI, 1.97 to 3.67) (P<0.001 for all comparisons). Similar associations were apparent for a range of nonvascular outcomes, including respiratory, digestive, and skin conditions (P<0.01 for all comparisons). No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death.
Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes. It is possible that severe hypoglycemia contributes to adverse outcomes, but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events. (Funded by Servier and the National Health and Medical Research Council of Australia; ClinicalTrials.gov number, NCT00145925.).
严重低血糖可能会增加 2 型糖尿病患者接受强化血糖降低干预后发生不良结局的风险。我们分析了一项大型强化血糖降低研究的数据，以探讨严重低血糖与不良临床结局之间的关系。
我们使用 Cox 比例风险模型，对 11140 例 2 型糖尿病患者的严重低血糖与大血管或微血管事件风险和死亡风险之间的关系进行了分析，该模型调整了基线和随机分组后测量的协变量。
在中位 5 年的随访期间，231 例（2.1%）患者至少发生过一次严重低血糖事件；150 例患者被分配到强化血糖控制组（占 5571 例患者的 2.7%），81 例患者被分配到标准血糖控制组（占 5569 例患者的 1.5%）。从严重低血糖发作到首次主要大血管事件、首次主要微血管事件和死亡的中位时间分别为 1.56 年（四分位距，0.84 至 2.41）、0.99 年（四分位距，0.40 至 2.17）和 1.05 年（四分位距，0.34 至 2.41）。随访期间，严重低血糖与主要大血管事件（风险比，2.88；95%置信区间[CI]，2.01 至 4.12）、主要微血管事件（风险比，1.81；95%CI，1.19 至 2.74）、心血管原因死亡（风险比，2.68；95%CI，1.72 至 4.19）和任何原因死亡（风险比，2.69；95%CI，1.97 至 3.67）的风险显著增加相关（所有比较 P<0.001）。对于一系列非血管结局，包括呼吸道、消化道和皮肤疾病，也存在类似的关联（所有比较 P<0.01）。严重低血糖反复发作与血管结局或死亡之间没有关系。
严重低血糖与一系列不良临床结局风险的增加密切相关。严重低血糖可能导致不良结局，但这些分析表明，低血糖也可能是发生此类事件的脆弱性标志物。（由 Servier 和澳大利亚国家卫生与医学研究委员会资助；ClinicalTrials.gov 编号，NCT00145925。）
