Tokutsu Akemi, Okada Yosuke, Torimoto Keiichi, Tanaka Yoshiya
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
Diabetol Metab Syndr. 2021 Apr 15;13(1):45. doi: 10.1186/s13098-021-00663-2.
HbA1c variability is independent of mean HbA1c, and associated with mortality due to vascular complications. However, the significance of HbA1c variability is unknown at present. In this study, we used flash glucose monitoring (FGM) and evaluated glycemic intraday variations, and then examined the association with HbA1c variability.
We conducted a retrospective pilot study of 26 patients treated at the Outpatient department for type 2 diabetes mellitus (T2DM), and evaluated the following items associated with blood glucose levels and their changes/variations using FGM. The primary endpoint was factor(s) associated with standard deviation (SD) HbA1c over a 6-month period. To adjust for the effect of varying numbers of HbA1c measurements, we used the adjusted SD of HbA1c.
There were significant correlations between mean HbA1c and each of glucose management indicator, maximum, percent time at glucose > 180 mg/day, mean of daily difference of blood glucose, and high blood glucose index. Adjusted SD HbA1c correlated significantly with percent time at glucose < 70 mg/dL and low blood glucose index. We estimated the regression coefficient of adjusted SD HbA1c using multivariate linear regression analysis, and noted that the presence of hypoglycemia affected Adjusted SD HbA1c (β = 0.130, SE = 0.044, P = 0.008). Hypoglycemia was noted in 17 patients, and adjusted SD HbA1c was significantly higher (p = 0.001) in the hypoglycemic group (0.22 ± 0.12%), compared with the non-hypoglycemic group (0.08 ± 0.05%). The cut-off value of adjusted SD HbA1c was 0.109% in the hypoglycemic group.
The results showed that HbA1c variability is associated with hypoglycemia. For patients with high HbA1c variability, we recommend evaluation for the presence of hypoglycemia and reconsideration of their treatment regimen including their glucose-lowering medications. Trial registration The study protocol and opt-out method of informed consent were approved by the ethics committees of the University of Occupational and Environmental Health (Trial registration: H27-186, Registered 25 Dec 2015).
糖化血红蛋白（HbA1c）变异性独立于平均HbA1c水平，且与血管并发症导致的死亡率相关。然而，目前HbA1c变异性的意义尚不清楚。在本研究中，我们使用动态血糖监测（FGM）评估日内血糖变化，进而研究其与HbA1c变异性的关系。
我们对26例在门诊接受2型糖尿病（T2DM）治疗的患者进行了一项回顾性试点研究，并使用FGM评估了与血糖水平及其变化相关的以下项目。主要终点是与6个月期间HbA1c标准差（SD）相关的因素。为校正HbA1c测量次数不同的影响，我们使用了校正后的HbA1c标准差。
平均HbA1c与各血糖管理指标、血糖最大值、血糖>180 mg/dl的时间百分比、血糖每日差值均值以及高血糖指数之间均存在显著相关性。校正后的HbA1c标准差与血糖<70 mg/dl的时间百分比以及低血糖指数显著相关。我们使用多元线性回归分析估计校正后的HbA1c标准差的回归系数，发现低血糖的存在会影响校正后的HbA1c标准差（β=0.130，SE=0.044，P=0.008）。17例患者出现低血糖，低血糖组校正后的HbA1c标准差（0.22±0.12%）显著高于非低血糖组（0.08±0.05%）（p=0.001）。低血糖组校正后的HbA1c标准差的截断值为0.109%。
结果表明，HbA1c变异性与低血糖相关。对于HbA1c变异性高的患者，我们建议评估是否存在低血糖，并重新考虑其治疗方案，包括降糖药物。试验注册本研究方案和知情同意退出方法已获得日本产业医科大学伦理委员会批准（试验注册：H27-186，2015年12月25日注册）。
