目的:低血糖是否会增加糖尿病患者其他不良结局的风险仍存在争议,特别是对于不需要他人帮助的低血糖发作。低血糖症重新定义SOLutions以获得更好的生命(Hypo-RESOLVE)项目的目的是创建并使用1型或2型糖尿病患者的汇总临床试验数据集,以检查暴露于所有低血糖发作之间的关联严重程度与事件结果:死亡,CVD,神经病,肾病,视网膜疾病和抑郁症。我们还检查了低血糖发作后发生的连续结局的变化:eGFR的变化,HbA1c,血糖,血糖变异性和体重。
方法:收集来自84项试验的39,373名参与者的数据。对于事件结果,根据年龄调整的时间更新的Cox回归模型,性别,对糖尿病持续时间和HbA1c进行了拟合,以评估:(1)结果与低血糖发作的累积暴露之间的关联;(2)可能会出现急性影响的结果(即死亡,急性CVD,视网膜疾病)和最近10天内的任何低血糖暴露。检查了任何低血糖发作和给定严重程度(1、2和3级)的发作。然后对更广泛的潜在混杂因素进行了进一步调整。还总结了连续结局的人内变化(1型糖尿病的中位数为40.4周,2型糖尿病的中位数为26周)。分别按糖尿病类型进行分析。
结果:对1型糖尿病的最大调整关联分析发现,任何水平的低血糖发作的累积暴露与神经病变的高风险相关,肾病,视网膜疾病和抑郁症,风险比范围为1.55(p=0.002)至2.81(p=0.002)。当分别检查1级发作时,发现了相似方向的关联,但仅对抑郁症有意义。对于2型糖尿病,任何水平的低血糖发作的累积暴露与更高的死亡风险相关。急性CVD,肾病,视网膜疾病和抑郁症,风险比范围为2.35(p<0.0001)至3.00(p<0.0001)。当分别检查1级发作时,这些关联仍然很重要。有证据表明,在过去的10天中,任何类型的低血糖发作与死亡之间存在关联,1型和2型糖尿病的急性CVD和视网膜疾病,比率范围为1.32(p=0.017)至2.68(p<0.0001)。当通过低血糖水平单独检查时,这些关联在大小和显著性上有所不同。在1、2和3级定义的低血糖范围内,我们找不到任何证据表明这些后果的风险突然变得明显的阈值。
结论:这些数据与低血糖与糖尿病患者多个身体系统的不良事件风险增加相关一致。这些关联并不局限于需要帮助的严重低血糖。
OBJECTIVE: Whether
hypoglycaemia increases the risk of other adverse outcomes in diabetes remains controversial, especially for
hypoglycaemia episodes not requiring assistance from another person. An objective of the
Hypoglycaemia REdefining SOLutions for better liVEs (Hypo-RESOLVE) project was to create and use a dataset of pooled clinical trials in people with type 1 or type 2 diabetes to examine the association of exposure to all hypoglycaemia episodes across the range of severity with incident event outcomes: death, CVD, neuropathy, kidney disease, retinal disorders and depression. We also examined the change in continuous outcomes that occurred following a
hypoglycaemia episode: change in eGFR, HbA1c, blood glucose, blood glucose variability and weight.
METHODS: Data from 84 trials with 39,373 participants were pooled. For event outcomes, time-updated Cox regression models adjusted for age, sex, diabetes duration and HbA1c were fitted to assess association between: (1) outcome and cumulative exposure to hypoglycaemia episodes; and (2) outcomes where an acute effect might be expected (i.e. death, acute CVD, retinal disorders) and any hypoglycaemia exposure within the last 10 days. Exposures to any hypoglycaemia episode and to episodes of given severity (levels 1, 2 and 3) were examined. Further adjustment was then made for a wider set of potential confounders. The within-person change in continuous outcomes was also summarised (median of 40.4 weeks for type 1 diabetes and 26 weeks for type 2 diabetes). Analyses were conducted separately by type of diabetes.
RESULTS: The maximally adjusted association analysis for type 1 diabetes found that cumulative exposure to hypoglycaemia episodes of any level was associated with higher risks of neuropathy, kidney disease, retinal disorders and depression, with risk ratios ranging from 1.55 (p=0.002) to 2.81 (p=0.002). Associations of a similar direction were found when level 1 episodes were examined separately but were significant for depression only. For type 2 diabetes cumulative exposure to hypoglycaemia episodes of any level was associated with higher risks of death, acute CVD, kidney disease, retinal disorders and depression, with risk ratios ranging from 2.35 (p<0.0001) to 3.00 (p<0.0001). These associations remained significant when level 1 episodes were examined separately. There was evidence of an association between hypoglycaemia episodes of any kind in the previous 10 days and death, acute CVD and retinal disorders in both type 1 and type 2 diabetes, with rate ratios ranging from 1.32 (p=0.017) to 2.68 (p<0.0001). These associations varied in magnitude and significance when examined separately by hypoglycaemia level. Within the range of hypoglycaemia defined by levels 1, 2 and 3, we could not find any evidence of a threshold at which risk of these consequences suddenly became pronounced.
CONCLUSIONS: These data are consistent with hypoglycaemia being associated with an increased risk of adverse events across several body systems in diabetes. These associations are not confined to severe
hypoglycaemia requiring assistance.