New biomarkers predict accelerated diabetic eye disease

Diabetic retinopathy (DR) is one of the late complications of diabetes and usually it affects people who have had diabetes for considerably longer duration. Research [1] from the Madras Diabetes Research Foundation (MDRF), India has now demonstrated that young onset type 2 diabetes patients possess an increased risk of developing diabetic retinopathy at an earlier stage and at a greater frequency accompanied by the elevated levels of certain biomarkers such as monocyte chemotactic protein 1 (MCP-1) and cathepsin-D.

Diabetes can lead to a wide variety of health complications, including heart disease, nerve damage, stroke, kidney disease, and vision loss. Diabetes is a risk factor for developing glaucoma, as well as for developing cataracts, but the most common and debilitating vision problem experienced by diabetics is diabetic retinopathy. The disease begins to damage the small blood vessels in the retina, the light-sensing layer of tissue in the back of the eye, causing them to leak fluid and blood. As the disease progresses, blood vessels become blocked and rupture or new vessels grow on the retina, leading to permanent and sometimes profound vision loss.

"Type 2 diabetes in younger adults represents an extreme phenotype with a paradoxically increasing trend in Asian Indians and these individuals are highly prone to the development of diabetic microvascular complications like diabetic retinopathy" -- says lead authors Muthuswamy Balasubramanyam & Viswanathan Mohan. This means 'earlier the onset of diabetes, faster and greater will be the vision problem'.

Earlier study from MDRF has reported a greater diabetic retinopathy prevalence of almost 52% in diabetic patients diagnosed with early onset of the disease. "The increased prevalence of diabetic retinopathy associated with early-onset diabetes is not simply a consequence of the longer duration of disease. We speculated that something specific to the diabetic milieu in younger patients might drive them and make them more prone to develop diabetic retinopathy" says Balasubramanyam. The two biomarkers MCP-1 and Cathepsin-D were progressively increased in diabetic patients with both non-proliferative and proliferative retinal disease. Correlation analysis revealed a positive association between MCP-1 and cathepsin-D levels. Interestingly, the study has also exposed a significant negative correlation of MCP1/cathepsin-D with C-peptide levels, implying certain level of early beta-cell dysfunction in these patients.

Although increased levels of vascular endothelial growth factor (VEGF) represent one of the foremost hallmarks of DR, VEGF inhibitors and VEGF-based intervention for DR have therapeutic limitations and hence it is important to look for biomarkers upstream of growth factor regulation. "While MCP-1 and cathepsin-D have both been proposed as biomarkers of angiogenic processes in other disease states, our work offers the first-line of data in the context of diabetic retinopathy that to in early-onset diabetic patients," says Balasubramanyam.

"It appears that higher levels of MCP-1 and cathepsin-D in young onset type 2 diabetes patients represent an accelerated aging phenotype -- a driving force for faster development of diabetic retinopathy. It is expected that targeting the pathways related to these biomarkers could be a future strategy for preventing the heightened risk of developing diabetic retinopathy in young-onset diabetic patients" -- concludes Balasubramanyam.