Experts Close in on Diabetic Retinopathy Cause
Researchers have found that a long-suspected molecule helps cause diabetic retinopathy, one of the leading causes of vision loss in the US, according to a report in the New England Journal of Medicine.
Some 700,000 Americans have diabetic retinopathy, with 63,000 new cases and 5,000 cases of diabetes-caused blindness every year, the authors say.
Diabetic retinopathy is caused by changes in the blood vessels of the retina. In some people with diabetic retinopathy, retinal blood vessels may swell and leak fluid, while in others, abnormal new blood vessels grow on the surface of the retina. These changes may result in vision loss or blindness.
Diabetic retinopathy cannot be completely avoided, but the risk can be greatly reduced. Better control of blood sugar level slows the onset and progression of retinopathy and reduces the need for laser surgery for severe retinopathy.
A person with an early stage of diabetic retinopathy may be asymptomatic [without symptoms] and without pain. Vision may not change until the disease progresses.
A condition called macular edema may occur when the macula, a part of the retina, swells from the leaking fluid and causes blurred vision. When new vessels grow on the surface of the retina, they can bleed into the eye, blocking vision.
The molecule found to be associated with diabetic retinopathy is erythropoietin, a protein hormone whose main function is to stimulate formation of red blood cells. The study by researchers at Kyoto University in Japan found excessively high levels of erythropoietin in the eye fluid of patients with diabetic retinopathy.
The 73 patients in the study, all of whom had diabetes, were in the last stages of retinopathy, in which overgrowth of blood vessels in the eye destroys vision. Levels of erythropoietin were more than 12 times higher in their eyes than in the eyes of 71 people without diabetes whose levels were also measured.
But the study also found that erythropoietin is just part of the molecular conspiracy that destroys vision in the diabetic eye.
The researchers detected extremely elevated levels of vascular endothelial growth factor (VEGF), another molecule that has long been identified as a contributor to diabetic retinopathy by stimulating blood vessel growth.
VEGF will occur in 60 percent of persons with diabetes unless something is done to prevent it, says an accompanying editorial in the journal by Dr. Lloyd Paul Aiello, who heads the section on eye research at the Joslin Diabetes Center in Boston.
"This is the first time folks have shown with extensive human data that erythropoietin is involved in diabetic retinopathy," Dr. Aiello notes. "Its action is independent of that of VEGF."
Attention has been focused on VEGF. Several medications designed to block its action are in advanced testing, and one has been approved by the US Food and Drug Administration (FDA) for use against a different cause of blindness, age-related macular degeneration, he says.
"But preclinical data suggests that VEGF might not be totally responsible, and this work now points out that another molecule is independently involved," Dr. Aiello says.
The finding opens a new area of research, he says, adding that "a good deal of work needs to be done to see if inhibiting erythropoietin can have a beneficial effect."
One issue is the safety of blocking erythropoietin in persons with diabetes, since there are studies indicating that it also acts to protect the retina from damage during times of stress, he explains.
"This is groundbreaking work," says Dr. John Loewenstein, associate chief of ophthalmology at the Massachusetts Eye and Ear Infirmary. "And like all groundbreaking work, it has to be confirmed by others. First it has to be confirmed by more experiments, and then we can look for inhibitors of erythropoietin."
Always consult your physician for more information.
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Two major health organizations in Europe and the US are calling for
closer examination of a syndrome that has been widely believed to predict the risk of developing heart
disease, questioning whether it has been appropriately defined and whether it is in fact a syndrome at
all.
In a joint paper published in Diabetes Care and Diabetologia, the American Diabetes Association and European Association for the Study of Diabetes argue that the metabolic syndrome - which has come to be regarded as a predictor of cardiovascular disease - is poorly defined, inconsistently used, and in need of further research to help understand whether and how it should be treated.
Physicians, the authors warn, should not be diagnosing people with this “syndrome” or attempting to treat it as a separate malady until the science behind it is clear.
“We shouldn’t be diagnosing people with the ‘metabolic syndrome,’" says Dr. Richard Kahn, chief scientific and medical officer of the American Diabetes Association.
"Doing so misleads the patient into believing he or she has a unique disease," he continues. "What they really have are well-known cardiovascular risk factors.
"The combination of risk factors does not add up to a more significant or higher cardiovascular risk than the individual components,” states Dr. Kahn.
The metabolic syndrome is often defined as having any three or more of the following:
a large waist circumference (more than 35 inches for women and more than 40 inches for men)
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high triglyceride levels (more than 150 mg/dl)
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high blood pressure (130/85 mm Hg or higher)
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low HDL (“good”) cholesterol (less than 50 mg/dl for women and less than 40 mg/dl for men)
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high blood glucose levels
The World Health Organization (WHO) offers a different definition, including anyone who has diabetes or insulin resistance and two of the following: high waist-to-hip ratio; high triglycerides or low HDL cholesterol; high blood pressure; and a high urinary albumin excretion rate.
Consequently, studies showing a correlation between a combination of these factors and the risk of developing heart disease are highly inconsistent, the authors say.
The fact that these are conflicting definitions implies that there is no clear evidence base for what should or should not be included, the authors note.
In patients with diabetes or known vascular disease, inordinate attention to the ‘metabolic syndrome’ can impede appropriate care, the authors report.
Similarly, treatment of each and every metabolic risk factor is indicated without requiring some arbitrary combination to drive clinical decision-making, they note.
“The metabolic syndrome requires much more study before its designation as a 'syndrome' is truly warranted and before its clinical utility is adequately defined,” the authors wrote in their conclusion.
Always consult your physician for more information.
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