Department of Endocrinology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
Department of Public Health, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
Medicine (Baltimore). 2022 Aug 19;101(33):e29942. doi: 10.1097/MD.0000000000029942.
Visit-to-visit variability (VVV) of glycated hemoglobin (HbA1c) levels have been found to be associated with prognosis of diabetes. However, little is known about whether or to what extent sex and age may modify the effects of VVV.
To investigate age- and sex-specific rates of mortality from all causes and relative hazards of mortality in association with VVV of HbA1c levels, 47,145 patients with diabetes and prescription of any antidiabetic agents >6 months were identified from outpatient visits of a tertiary medical center in northern Taiwan during 2003-2018. VVV of HbA1c was measured by quartiles of standard deviation (SD), coefficient of variation (CV), and average real variability (ARV), respectively. The study subjects were linked to Taiwan's National Death Registry to identify all-cause mortality. The person-year approach with the Poisson assumption was used to assess the all-cause mortality rates, and Cox proportional hazard regression model was used to evaluate the relative hazards of all-cause mortality concerning various levels of VVV of HbA1c.
The lowest all-cause mortality rate was found in either the first or second quartile of various measures for VVV of HbA1c, but the highest mortality rate was consistently observed in the fourth quartile of VVV, regardless of SD, CV, or ARV across ages and sexes. Increased hazards of overall all-cause mortality were noticed from the second to fourth quartile of VVV of HbA1c. In detailed age- and sex-stratified analyses, elevated risk of mortality was seen in the fourth quartile of those aged <50 years while in those aged >69 years, increased risk of mortality was noticed in the third and fourth quartiles of any VVV of HbA1c irrespective of sex. In those aged 50-69 years, incremental increased hazards of mortality were consistently observed in the second to fourth quartiles of VVV of HbA1c.
HbA1c variability whether it was SD, CV, or ARV could strongly predict the risks of all-cause mortality. The extent of the relationship between VVV of HbA1c and all-cause mortality in different age groups was comparable between both sexes. Given the importance of long-term glucose fluctuation, the inclusion of HbA1c variability calculated from the standardized method should be considered by clinical guideline policymakers as part of the biochemical panel in daily diabetes management.
糖化血红蛋白（HbA1c）水平的变异性与糖尿病的预后有关。然而，关于性别和年龄是否会影响 HbA1c 水平变异性的影响程度，知之甚少。
为了研究年龄和性别特异性全因死亡率以及与 HbA1c 水平变异性相关的死亡率的相对危险度，我们从台湾北部一家三级医疗中心的门诊就诊患者中确定了 47145 名患有糖尿病且服用任何抗糖尿病药物>6 个月的患者。分别使用标准差（SD）、变异系数（CV）和平均真实变异性（ARV）的四分位距来测量 HbA1c 的变异性。研究对象与台湾国家死亡登记处相关联，以确定全因死亡率。采用泊松假设的人年方法评估全因死亡率，采用 Cox 比例风险回归模型评估 HbA1c 变异性各水平与全因死亡率的相对危险度。
在各种 HbA1c 变异性的第一或第二四分位数中发现全因死亡率最低，但无论 SD、CV 或 ARV 如何，在年龄和性别中，第四四分位数的死亡率始终最高。从 HbA1c 变异性的第二到第四四分位数观察到全因死亡率的危险度增加。在详细的年龄和性别分层分析中，在<50 岁的人群中，第四四分位数的死亡率风险升高，而在>69 岁的人群中，无论性别如何，第三和第四四分位数的任何 HbA1c 变异性都注意到死亡率风险增加。在 50-69 岁的人群中，在 HbA1c 变异性的第二到第四四分位数中，始终观察到死亡率危险度的递增。
HbA1c 变异性（无论是 SD、CV 还是 ARV）都可以强烈预测全因死亡率的风险。不同年龄组之间 HbA1c 变异性与全因死亡率之间的关系程度在两性之间相当。鉴于长期血糖波动的重要性，临床指南制定者应考虑将基于标准化方法计算的 HbA1c 变异性纳入日常糖尿病管理的生化指标。
