AUG 07, 2012
This prospective study found a significant association between advanced glycation end product (AGE)–LDL and oxidized LDL (oxLDL) immunocomplex (IC) levels and retinopathy progression in patients with type 1 diabetes.
The authors measured the IC levels of AGE-LDL and oxLDL in 517 patients from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications cohort. Retinopathy was assessed by stereoscopic fundus photography. Cox proportional hazards models were used to assess the effect of AGE-LDL-ICs and oxLDL-ICs on retinopathy progression.
After adjustment by study design variables and conventional risk factors, a significant relationship was found between high levels of AGE-LDL-ICs and oxLDL-ICs and progression to proliferative diabetic retinopathy, as well as to severe nonproliferative diabetic retinopathy. Specifically, one SD increase in IC levels was associated with a 47 percent and 45 percent increased risk of developing proliferative diabetic retinopathy for AGE-LDL-ICs and oxLDL-ICs, respectively, and a 37 percent increased risk (for both ICs) of progressing to severe nonproliferative retinopathy.
The authors write that AGE-LDL and oxLDL-containing ICs likely play a role in enhancing retinal leukostasis. Other possible mechanisms by which oxLDL and AGE-LDL–containing ICs may contribute to the changes observed in diabetic retinopathy include stimulation of growth factors and production of matrix proteins, leading to thickening of the retinal vascular basement membrane.
They conclude that further studies are needed to clearly detail the pathogenic mechanisms by which ICs containing AGE-LDL and oxLDL contribute to the development of diabetic retinopathy. However, this study provides strong clinical evidence that a link likely exists between their formation and/or deposition in the retina and the accelerated progression to retinopathy in patients with type 1 diabetes.