Long-term HbA1c variability and the development and progression of diabetic retinopathy in subjects with type 2 diabetes

Abstract

This study aimed to investigate whether long-term HbA1c variability is associated with the development and progression of diabetic retinopathy (DR) in subjects with type 2 diabetes. We retrospectively reviewed 434 type 2 diabetes subjects without DR who underwent regular DR screening. We reviewed fundus findings, collected HbA1c levels, and calculated the coefficient of variation (CV) and average real variability (ARV) of each subject's HbA1c level. DR was developed in 55 subjects and progressed to moderate nonproliferative DR or worse DR in 23 subjects. On Cox proportional hazards regression analysis, HbA1c ARV, but not HbA1c CV, was significantly associated with DR development. However, the association between HbA1c variability and the DR progression rate to moderate nonproliferative DR or worse DR was not significant. The inter-visit HbA1c difference value on consecutive examination predicted DR development well and more careful screening for DR is needed for those with an absolute value change of 2.05%, an absolute increase of 1.75%, and an absolute decrease of 1.45% in HbA1c levels on consecutive examination. These results indicate that long-term glucose variability measured by HbA1c ARV might be an independent risk factor for DR development in addition to the mean HbA1c level in early diabetic subjects.

Figure 1

Schematic diagram for study design, inclusion criteria, and study flow chart. (A) Study design and timeline of the study. The date of the first fundus examination was designated as the baseline. The overlap period was defined as the length of the period when both serial fundus examination for diabetic retinopathy (DR) screening and serial HbA1c measurement were performed. (B) Inclusion criteria. The examination index was defined as the ratio of the overlap period to the fundus examination period, and in this study, only those with an examination index over 0.9 were included. (C) Study flow chart. After excluding those with insufficient examinations or a short follow-up period, 434 subjects were finally enrolled in this study.

Figure 2

Comparison of development and progression rate of diabetic retinopathy (DR) according to the mean and average real variability (ARV) of HbA1c level. (A) Subject grouping according to their mean and ARV value of HbA1c. The mean and ARV of HbA1c showed a significant positive correlation (r = 0.588, p < 0.001). (B,C) Comparison of the rate of the DR development (B) and DR progression to moderate nonproliferative DR or worse DR (C) in four groups.

Figure 3

Receiver operating characteristic (ROC) curve for predicting diabetic retinopathy development using inter-visit HbA1c differences. (A) The ROC curve of the absolute inter-visit HbA1c level difference, (B) The ROC curve of the increase in HbA1c difference, (C) The ROC curve of the decrease in HbA1c difference. AUC, area under the curve.