Diabetic Retinopathy Linked to Inflammatory Markers

The investigators, headed by Dr. Barbara E. K. Klein from the University of Wisconsin School of Medicine and Public Health in Madison, stated that, "Traditional risk factors -- blood glucose levels, hypertension, and total cholesterol -- account for only a small portion of the incidence and progression of diabetic retinopathy in Type 1 diabetes."

People with diabetes tend to have elevated levels of cytokines and endothelial markers. Dr. Klein's group investigated the association of these biomarkers with diabetic retinal outcomes during long-term follow-up.

The study cohort was comprised of patients diagnosed with Type 1 diabetes before age 30. Included were 671 patients from whom serum samples were obtained and frozen in 1990-1992, with follow-up through 2005-2007.

From these samples the researchers determined levels of the inflammatory markers high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor. They also measured markers of endothelial dysfunction -- total homocysteine, soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (slCAM-1).

In cross-sectional analysis, when comparing the highest and lowest quartiles, serum levels of tumor necrosis factor (odds ratio, 5.46), total homocysteine (OR 7.46), and sVCAM-1 (OR 3.95) were associated with increased prevalence or more severe retinopathy, after controlling for conventional risk factors. Similar odds were found for proliferative diabetic retinopathy as well.

"These results are important," the team notes. "They indicate that, even in those with kidney disease, a complication that itself is associated with elevated markers of systemic inflammation and endothelial dysfunction, relatively high levels (of the markers) are associated with markedly elevated odds ratios for increasing severity of diabetic retinopathy and progression to diabetic retinopathy."

Total homocysteine level was also associated with increased odds of macular edema, irrespective of kidney disease.

The authors suggest that "There is a different pathophysiological process associated with retinal thickening compared with specific lesions of diabetic retinopathy that is operative in persons with Type 1 diabetes mellitus, irrespective of kidney function."

However, none of the markers was associated with incidence of proliferative diabetic retinopathy, macular edema, or progression of diabetic retinopathy 15 years later.

Dr. Klein and associates conclude, "More research is needed to understand whether the markers themselves or, perhaps more likely, the systemic causes of these elevated marker levels, are causally associated with the severity of diabetic retinopathy."