OBJECTIVE The association between high glycemic variability and all-cause mortality has been widely investigated in epidemiological studies but rarely validated in glucose-lowering clinical trials. We aimed to identify the prognostic significance of visit-to-visit HbA1c variability in treated patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial population. RESEARCH DESIGN AND METHODS We studied the risk of all-cause mortality in relation to long-term visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV), from the 8th month to the transition from intensive to standard glycemic therapy. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (HR) and 95% CI. RESULTS Compared with the standard therapy group (n = 4,728), the intensive therapy group (n = 4,755) had significantly lower mean HbA1c (6.6% [49 mmol/mol] vs. 7.7% [61 mmol/mol], P < 0.0001) and lower CV, VIM, and ARV (P < 0.0001). In multivariate adjusted analysis, all three HbA1c variability indices were significantly associated with total mortality in all patients as well as in the standard- and intensive-therapy groups analyzed separately. The hazard ratios for a 1-SD increase in HbA1c variability indices for all-cause mortality were 1.19 and 1.23 in intensive and standard therapy, respectively. Cross-tabulation analysis showed the third tertile of HbA1c mean and VIM had significantly higher all-cause mortality (HR 2.05; 95% CI 1.17-3.61; P < 0.01) only in the intensive-therapy group. CONCLUSIONS Long-term visit-to-visit HbA1c variability was a strong predictor of all-cause mortality. HbA1c VIM combined with HbA1c mean conferred an increased risk for all-cause mortality in the intensive-therapy group.

中文翻译：

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在ACCORD试验中，长期全基因死亡率的HbA1c变异的预后意义。

目的在流行病学研究中已广泛研究了高血糖变异性与全因死亡率之间的关联，但在降低血糖的临床试验中很少得到证实。我们的目的是在控制糖尿病风险的心血管活动（ACCORD）试验人群中确定接受治疗的患者访视HbA1c变异的预后意义。研究设计与方法我们研究了与长期就诊HbA1c变异性相关的全因死亡率的风险，以变异系数（CV），独立于均值（VIM）的变异性和平均实际变异性（ ARV），从第8个月到从强化血糖治疗到标准血糖治疗的过渡。使用多变量Cox比例风险模型估算调整后的风险比（HR）和95％CI。结果与标准治疗组（n = 4,728）相比，强化治疗组（n = 4,755）的平均HbA1c明显较低（6.6％[49 mmol / mol]比7.7％[61 mmol / mol]，P <0.0001） ）并降低CV，VIM和ARV（P <0.0001）。在多变量校正分析中，所有三个患者以及分别进行分析的标准治疗和强化治疗组的所有三个HbA1c变异性指数均与总死亡率显着相关。在强化治疗和标准治疗中，全因死亡率的HbA1c变异性指数1-SD升高的危险比分别为1.19和1.23。交叉表分析显示，仅在强化治疗组中，HbA1c平均值的第三位和VIM的全因死亡率显着较高（HR 2.05； 95％CI 1.17-3.61； P <0.01）。结论长期随访HbA1c变异性是全因死亡率的有力预测指标。HbA1c VIM联合HbA1c意味着强化治疗组的全因死亡率增加了风险。