Chi Xu,1,2 Wu Dai,1 Yan Liu,1 Rong Zhang,1 Erlan Shi,1 Xiangxiang Shan,1 Yonghong Cao1,2 

1Department of Endocrinology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, 230011, People’s Republic of China; 2The Fifth Clinical Medical College, Anhui Medical University, Hefei, 230032, People’s Republic of China

Correspondence: Yonghong Cao, Department of Endocrinology, Hefei Hospital Affiliated to Anhui Medical University (Hefei Second People’s Hospital), Hefei, 230011, People’s Republic of China, Email fish1982cao@126.com

Aim: Our study aimed to investigate the association between time in range (TIR) and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) patients with hypoglycemia unawareness.
Methods: This is a retrospective cross-sectional study. In our study, 298 T2DM patients with hypoglycemia unawareness were recruited from the Department of Endocrinology, Hefei Second People’s Hospital from 01/09/2020 to 30/06/2023. Patients were divided into DR group (97 cases) and non-DR group (NDR, 201 cases). We compared the clinical data and blood glucose fluctuation indexes of the two groups. Meanwhile, we also observed these indicators, especially the prevalence of DR and the time below range (TBR) in groups with different TIR levels (Q1 group: TIR≤ 70%, 79 cases; Q2 group: 70% 95%, 74 cases). The influencing factors of DR in T2DM patients with hypoglycemia unawareness were analyzed by logistic regression.
Results: TIR of DR group was significantly lower than that of NDR group (P< 0.05). And TIR was an independent protective factor for DR after correcting confounding factors in logistic regression analysis (OR=0.937, P=0.032). ROC curve showed that the AUC of TIR for DR diagnosis prediction was 0.756. The comparison among TIR groups showed that the prevalence of DR in Q1 group was higher than that in Q2 to Q4 group; and the TBR in Q3 group was higher than that in other TIR groups (P< 0.05). Spearman analysis showed that TBR was negatively correlated with MG (r=− 0.221, P< 0.001). Only Q1 group (TIR≤ 70%) was a risk factor for DR in logistic regression with Q3 group as the reference group.
Conclusion: Lower TIR is associated with an increased risk of DR in T2DM patients with hypoglycemia unawareness. After weighing the risk of DR and TBR, TIR at 70– 85% is the satisfactory range for T2DM patients with hypoglycemia unawareness.

Keywords: T2DM, hypoglycemia unawareness, time in range, time below range, diabetic retinopathy