The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study.
The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study.
复制标题
DOI：
10.1136/bmj.b4909
复制
发表时间：
2010-01-08
期刊：
影响因子：
--
通讯作者：
Sweeney ME
中科院分区：
文献类型：
--
作者：
Bonds DE;Miller ME;Bergenstal RM;Buse JB;Byington RP;Cutler JA;Dudl RJ;Ismail-Beigi F;Kimel AR;Hoogwerf B;Horowitz KR;Savage PJ;Seaquist ER;Simmons DL;Sivitz WI;Speril-Hillen JM;Sweeney ME
目的探讨控制糖尿病心血管风险行动（雅阁）试验参与者的低血糖与死亡率之间是否存在联系。设计回顾性流行病学分析的数据从雅阁试验。设置糖尿病诊所，研究诊所和初级保健诊所。参与者如果患者患有2型糖尿病，筛选期间糖化血红蛋白（血红蛋白A1 C）浓度为7.5%或更高，并且年龄为40-79岁，患有心血管疾病或55-79岁，有亚临床疾病或两个额外的心血管风险因素的证据，则有资格参加雅阁研究。 强化干预（血红蛋白A1 C <6.0%）或标准（血红蛋白A1 C 7.0-7.9%）血糖控制。结果测量症状，严重低血糖，表现为血糖浓度低于2.8 mmol/l（<50 mg/dl）或经治疗后消退且需要他人协助或医疗协助的症状，以及所有原因和原因特异性死亡率，包括对低血糖参与的特定评估。 结果10251名参加雅阁研究的参与者中有10194名参与者在定期随访生命状态期间至少有一次低血糖评估。在强化血糖控制组中，发生一次或多次低血糖发作需要任何帮助的患者的未校正年死亡率为2.8%，而未发生低血糖发作的患者的未校正年死亡率为1.2（分别为53例死亡/1924人年和201例死亡/16315人年;调整后风险比（HR）1.41，95% CI 1.03 - 1.93）。在标准血糖控制组的参与者中观察到类似的模式（3.7%（每564人年21例死亡）vs 1.0%（每17297人年176例死亡）;校正的HR 2.30，95% CI 1.46至3.65）。另一方面，在至少发生1次需要任何帮助的低血糖发作的受试者中，强化治疗组的死亡风险低于标准治疗组，但无显著性差异（校正HR 0.74，95% 0.46 - 1.23）。与标准组相比，在至少发生过一次需要医疗救助的低血糖发作的受试者中，观察到强化组的风险显著降低（校正HR 0.55，95% CI 0.31 - 0.99）。截至强化治疗组关闭时，在雅阁中发生的451例死亡中，1例死亡被裁定为与低血糖明确相关。结论：在每个研究组中，症状性重度低血糖与死亡风险增加相关。然而，在至少经历过一次低血糖发作的参与者中，强化组中此类参与者的死亡风险低于标准组。严重低血糖似乎不能解释两个研究组之间死亡率的差异，直到雅阁强化低血糖组被停止了。试验注册NCT 00000620。
Objective To determine whether there is a link between hypoglycaemia and mortality among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Design Retrospective epidemiological analysis of data from the ACCORD trial. Setting Diabetes clinics, research clinics, and primary care clinics. Participants Patients were eligible for the ACCORD study if they had type 2 diabetes, a glycated haemoglobin (haemoglobin A1C) concentration of 7.5% or more during screening, and were aged 40-79 years with established cardiovascular disease or 55-79 years with evidence of subclinical disease or two additional cardiovascular risk factors. Intervention Intensive (haemoglobin A1C <6.0%) or standard (haemoglobin A1C 7.0-7.9%) glucose control. Outcome measures Symptomatic, severe hypoglycaemia, manifest as either blood glucose concentration of less than 2.8 mmol/l (<50 mg/dl) or symptoms that resolved with treatment and that required either the assistance of another person or medical assistance, and all cause and cause specific mortality, including a specific assessment for involvement of hypoglycaemia. Results 10 194 of the 10 251 participants enrolled in the ACCORD study who had at least one assessment for hypoglycaemia during regular follow-up for vital status were included in this analysis. Unadjusted annual mortality among patients in the intensive glucose control arm was 2.8% in those who had one or more episodes of hypoglycaemia requiring any assistance compared with 1.2% for those with no episodes (53 deaths per 1924 person years and 201 deaths per 16 315 person years, respectively; adjusted hazard ratio (HR) 1.41, 95% CI 1.03 to 1.93). A similar pattern was seen among participants in the standard glucose control arm (3.7% (21 deaths per 564 person years) v 1.0% (176 deaths per 17 297 person years); adjusted HR 2.30, 95% CI 1.46 to 3.65). On the other hand, among participants with at least one hypoglycaemic episode requiring any assistance, a non-significantly lower risk of death was seen in those in the intensive arm compared with those in the standard arm (adjusted HR 0.74, 95% 0.46 to 1.23). A significantly lower risk was observed in the intensive arm compared with the standard arm in participants who had experienced at least one hypoglycaemic episode requiring medical assistance (adjusted HR 0.55, 95% CI 0.31 to 0.99). Of the 451 deaths that occurred in ACCORD up to the time when the intensive treatment arm was closed, one death was adjudicated as definitely related to hypoglycaemia. Conclusion Symptomatic, severe hypoglycaemia was associated with an increased risk of death within each study arm. However, among participants who experienced at least one episode of hypoglycaemia, the risk of death was lower in such participants in the intensive arm than in the standard arm. Symptomatic, severe hypoglycaemia does not appear to account for the difference in mortality between the two study arms up to the time when the ACCORD intensive glycaemia arm was discontinued. Trial registration NCT00000620.