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Fifty Years with Diabetes and No Retinopathy

Posted: Wednesday, November 03, 2010

Many long-term survivors with diabetes show little or no progression of retinopathy after a certain point, and this resistance apparently has nothing to do with glycemic control, a researcher found.

A new study of "Medalists" -- a cohort of diabetes patients who have lived for 50 years or more with the disease, assembled by the Joslin Diabetes Center in Boston -- indicated that about half did not have proliferative diabetic retinopathy, and those individuals almost never showed any worsening of eye disease after the first 17 years.

Jennifer K. Sun, MD, MPH, of Harvard Medical School stated that, "The degree of glycemic control, as indicated by HbA1c levels, did not significantly predict which Medalist participants would develop proliferative retinopathy… It goes against every other diabetes study we've ever seen," Sun said.

Prospective studies such as ACCORD and the UKPDS have documented very strong correlations between lack of glycemic control and higher rates of complications, including retinopathy.

But Sun noted that glycemic control was not a central factor in diabetes treatment until relatively recently. As a result, Medalists are those who have survived -- for reasons that the Joslin program was formed to identify -- despite decades of presumably frequent excursions into hyperglycemia.

The other important finding was that decreased expression of a signaling molecule called SHP-1 was significantly associated with protection against development of retinopathy.

SHP-1 is a tyrosine phosphatase molecule involved in a variety of cellular processes, Sun explained. She said previous studies have indicated that its activity is increased in response to hyperglycemia, prefiguring apoptosis in certain retinal cells.

"The thought is that the activation of SHP-1 kind of tips the balance between pathways for cellular survival and pathways that lead to cellular death," Sun said. "We think that SHP-1 may be involved in some of the early processes of diabetes," including retinopathy.

Her study focused on 97 out of several hundred current Medalists, who not only had survived at least 50 years with diabetes but also had routine ophthalmic evaluations in an eye clinic associated with Joslin. The mean period covered by these exams was 20.6 years.

Records of these visits indicated that worsening of retinopathy was almost entirely confined to the first 17 years of ophthalmic follow-up, according to Sun.

She and her colleagues found that of 94 eyes in the cohort that did not develop proliferative disease, about 60% didn't worsen at all and of the remainder that did, only one showed worsening after the first 17 years.

On the other hand, of 54 eyes that eventually did develop proliferative disease, progression occurred early. More than 90% showed worsening disease within 20 years.

Although HbA1c levels did not predict which patients would develop proliferative disease, SHP-1 did, at least to an extent.

Individuals with relatively high levels of SHP-1 expression were from two to four times more likely to have proliferative retinopathy with disease duration of about 35 to 50 years, but with longer duration, the effect shrank.

Low levels were also significantly (P=0.004) associated with lower rates of any diabetic retinopathy development, Sun indicated.

Sun said the presumption is that the patients without proliferative disease have protective factors -- such as, perhaps, low SHP-1 expression -- that allow them to avoid the diabetic complications that end up killing most patients with the disease.

Not only do about 40% of the Medalists appear to have little or mild retinopathy, but the severity of the three other major types of complications -- cardiovascular, renal, and neurological -- is similarly low, she said.

The researchers are now looking more systematically at proteomic and genomic factors that may distinguish Medalists from diabetics with shorter disease duration, Sun said.
Practice Pearls:

    * Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

    * Note that this study of long-term survivors with diabetes shows that if progression of proliferative retinopathy did not occur in the first 17 years after diagnosis, it was not likely to progress after much longer follow-up.

Source: http://www.diabetesincontrol.com/index.php?option=com_content&view=article&id=10000&catid=53&Itemid=8, Sun J, et al "Reduced diabetic retinopathy progression in patients with 50 or more years of diabetes (Medalists) and nonproliferative diabetic retinopathy" AAO 2010; Abstract PO221.

 
 
 
 
 
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