N‐glycosylation of disease‐specific haptoglobin for the early screening of diabetic retinopathy

Purpose Diabetic retinopathy (DR), as one of the microvascular complications of diabetes, is a leading cause of acquired vision loss. Most DR cases are detected in the advanced stage through fundoscopy, making molecular biomarkers urgently needed for early diagnosis of DR. Experimental design Serum disease‐specific haptoglobin‐β (Hp‐β) chains of 100 patients with type 2 diabetes mellitus (T2DM) and 156 T2DM patients with non‐proliferative diabetic retinopathy (NPDR) were separated using polyacrylamide gel electrophoresis. After in‐gel digestion and enrichment, the intact N ‐glycopeptides were detected by mass spectrometry. Results Fucosylation of Hp‐β was significantly increased and sialylation of Hp‐β was significantly decreased in background DR (BDR, an early‐stage DR) patients compared with non‐diabetic retinopathy patients ( p < 0.05) and yielded area under curves (AUCs) of 0.801 and 0.829 in training and validation groups, respectively, which had an advantage over glycated hemoglobin A1c (AUC ≤ 0.691). Moreover, a significant increase in sialylated Hp‐β was found in severe NPDR patients compared with BDR patients and yielded an AUC of 0.828 to distinguish severe NPDR from BDR. Conclusion Changes in Hp‐β glycosylation are closely related to DR, and may be used for early diagnosis and screening of DR.