Staying a Step Ahead of Diabetes Eye Damage
A few simple blood tests for measuring risk factors
By A.Paul Chous, MA, OD, FAAO
A number of factors have been linked to the development and worsening of diabetic retinopathy, including the length of time a person has had diabetes, higher blood glucose levels, higher blood pressure and abnormal blood lipids (higher ‘bad' LDL cholesterol and triglycerides). There is now increasing interest in predicting which patients are most likely to develop diabetes-related eye disease, so that efforts can be directed at improving risk factors and toward monitoring high-risk patients more closely, so that vision-saving treatments like laser therapy can be performed before permanent vision loss occurs. Here, I'd like to familiarize you with some simple blood tests for measuring these newly identified risk factors.
A recent study appearing in Archives of Ophthalmology has suggested that higher hemoglobin levels are associated with an increased risk of proliferative diabetic retinopathy(1), the most serious form of the disease. Hemoglobin is the protein molecule contained within red blood cells (RBCs) that carries inhaled oxygen from the lungs to body tissues, and then returns carbon dioxide from those tissues back to the lungs to be exhaled. The study found that each 1 point rise (g/dl) in blood hemoglobin increased the risk of diabetic retinopathy in men with type 1 diabetes by 29% and in women by 10%. A number of factors may account for increased levels of hemoglobin in these patients, including an increased total number of red blood cells, or oxygen starvation in body tissues (known as hypoxia) caused by vascular damage. Hemoglobin levels are routinely measured when your physician orders a complete blood count (CBC). This is totally distinct from the hemoglobin A1C test, which measures the amount of glucose bound to a specific portion of hemoglobin molecules within our red blood cells and reflects average blood glucose levels over a two- to three-month period. Interestingly, retinopathy also has been linked to levels of hemoglobin that are too low (anemia).
Tumor Necrosis Factor Alpha
Another blood protein linked to increased risk of retinopathy is called tumor necrosis factor alpha (TNF-). This protein is associated with systemic inflammation and is primarily involved in regulating immune cells, including those which inhibit cancer cell growth. In one study of children with diabetes, higher levels of TNF- quadrupled the risk of having non-proliferative retinopathy.(2) In a Swedish study of older type 1 patients, TNF- was strongly associated with proliferative retinopathy, while a Korean study showed the same association in patients with type 2 diabetes.(3) Blood tests for measuring TNF- is becoming increasingly common, as it has been linked to autoimmune conditions like rheumatoid arthritis, and several TNF- inhibitors are now commercially available (e.g. Embrel). Interestingly, the statin drugs appear to lower TNF- levels in human retinal cells and may help prevent leakage of blood and fluid in diabetic retinopathy.(4)
Homocysteine is an amino acid found in the blood that appears to be associated with a higher risk of heart disease and stroke. A follow-up to the Wisconsin Epidemiology of Diabetic Retinopathy study (WESDR) showed that increased homocysteine nearly quadrupled the risk of < a href="http://www.dlife.com/diabetes/information/complications/eye-care/macular-edema.html">diabetic macular edema(fluid swelling within the central retina).(5) The Multi-ethnic Study of Atherosclerosis (MESA) study also found an association between homocysteine and proliferative retinopathy.(6) It is important to note, however, that the authors of both these studies found only a small added benefit for predicting diabetic retinopathy by measuring blood levels of either TNF- or homocysteine after adjusting for other established risk factors like HbA1c, duration of diabetes and blood pressure. Levels of homocysteine can be lowered in many patients by taking folic acid supplements.
The use of novel blood tests for predicting a patient's risk for developing diabetic retinopathy is alluring, but it should not distract us from the basics of good diabetes management and prevention of complications, including eye disease: good blood sugar, blood pressure and blood lipid control, and regular appointments with your health care team, including the eye doctor. It still appears that the best predictor is, in fact, a relatively simple and very common blood test - glycosylated hemoglobin (HbA1c). Newer blood tests do hold some promise, however. Not only for prediction but, perhaps even more importantly, for clarifying the causes of retinopathy that will lead to earlier and more effective treatments.
For more information on diabetic eye disease, consult Dr. Chous' book Diabetic Eye Disease: Lessons From a Diabetic Eye Doctor, Fairwood Press, Seattle, 2003.
NOTE: The information is not intended to be a replacement or substitute for consultation with a qualified medical professional or for professional medical advice related to diabetes or another medical condition. Please contact your physician or medical professional with any questions and concerns about your medical condition.
1 - Arch Ophthalmol. 2009 Nov;127(11): 1494-9.
2 - Mediators Inflamm. 2007;2007:92196
3 - Ann Clin Lab Sci. 2008 Autumn;38(4):361-7.
4 - Exp Eye Res. 2009 Jun 15;89(1):71-8
5 - Arch Ophthalmol. 20009 Sep;127(9):1175-82
6 - Diabetes Care. 2009 Sep;32(9):1704-9
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