Relationship Between Glycemic Intraday Variations Evaluated in Continuous Glucose Monitoring and HbA1c Variability in Type 2 Diabetes: Pilot Study
Abstract Background: 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.Methods: 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 six-month period. Results: There were significant correlations between mean HbA1c and each of glucose management indicator, maximum, percent time at glucose >180 mg/d, mean of daily difference of blood glucose, and high blood glucose index. SD HbA1c correlated significantly with percent time at glucose <70 mg/dL and low blood glucose index. We estimated the regression coefficient of SD HbA1c using multivariate linear regression analysis, and noted that the presence of hypoglycemia affected SD HbA1c (β=0.132, SE=0.055, P=0.026). Hypoglycemia was noted in 17 patients, and SD HbA1c was significantly higher (p<0.001) in the hypoglycemic group (0.24±0.13%), compared with the non-hypoglycemic group (0.09±0.06%). The cut-off value of SD HbA1c was 0.126% in the hypoglycemic group.Conclusions: The results showed that HbA1c variability is associated with hypoglycemia. HbA1c variability reflects the risk of hypoglycemia, suggesting a possible association with the risk of cardiovascular mortality. 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).