Pilot Trial Confirms Insulin's Role in Inhibiting Leading Cause of Blindness in Adults

BUFFALO, N.Y. -- Endocrinologists from the University at Buffalo have shown for the first time that insulin suppresses production of vascular endothelial growth factor (VEGF), a compound known to play a role in the development of blindness in persons with diabetes, a condition called diabetic retinopathy.

In addition, they found that insulin suppresses production of an enzyme known as MMP (matrix metalloproteinase) that works in concert with VEGF, helping to induce retinopathy.

Results of the study were presented at the recent annual meeting of the Endocrine Society held in Philadelphia and at the preceding American Diabetes Association meeting in New Orleans.

""Since VEGF and MMP contribute to the development of retinopathy, the suppression of these factors by insulin may provide a new role for insulin in the prevention of diabetic retinopathy," said lead author Paresh Dandona, professor in the Department of Medicine in the UB School of Medicine and Biomedical Sciences and director of the Diabetes-Endocrine Center of Western New York at Kaleida Health.

Diabetic retinopathy is the leading cause of blindness in adults. It begins with deterioration of the small blood vessels in the eye, which leak fluid and lipids (fat cells) onto the retina, causing blurred vision. As the condition progresses, fragile new blood vessels proliferate along the retina and into the vitreous humor, the clear gel-like substance that fills the inside of the eye, in a process called angiogenesis.

If the condition remains untreated, these tiny blood vessels bleed into the eye, destroying the retina and causing blindness.

Diabetes in adults - Type 2 diabetes -- is characterized by the body's inability to use insulin to metabolize sugar, which results in a toxic accumulation of glucose in the bloodstream.

The condition is associated closely with obesity; research has shown that increased storage of fat molecules in fatty tissue causes insulin resistance, a condition that progresses to diabetes if untreated.

To test the effect of insulin on the concentration of VEGF, and by extension, its potential to induce angiogenesis, the UB researchers infused insulin in a dextrose solution into 10 fasting, obese non-diabetic subjects for four hours. Following the insulin challenge, subjects received only the dextrose solution without insulin, which served a control. Blood samples were taken prior to infusions and at two, four and six hours after the start of infusions.

Analysis of samples showed that as insulin levels increased, levels of the angiogenesis inducers VEGF and MMP decreased. At the two-hour mark, VEGF decreased an average of 27 percent from the baseline concentration, results showed. By 4 hours, when insulin had been fully infused, VEGF had dropped to an average of 32 percent below baseline. By two hours post infusion, VEGF was rising again toward baseline levels.

MMP concentrations also decreased as insulin increased, but less significantly, dropping a maximum of 18 percent on average, which was measured at the 4-hour mark. There was no decrease in either compound when subjects were infused with the dextrose solution alone, analysis showed.

Angiogenesis is known to contribute to atherosclerosis, a condition in addition to retinopathy that is associated with diabetes, Dandona said.

"We now know that when there is hardening of the arteries, new vessels form in the arterial walls. These new vessels support the growth of arterial plaque and contribute to blood clots and additional blockage of arteries.

"The data in this study are consistent with a potential neovascular suppressive effect of insulin," Dandona said. "These findings may indicate a potential role for insulin as an antiretinopathic and antisclerotic in general, and could lead to new treatments for diabetic retinopathy in particular."

Additional researchers on the study were Ahmad Aljada, Ph.D., UB research assistant professor of medicine; Priya Mohanty, M.D. UB clinical instructor of medicine; Husam Ghanim, UB doctoral student working with Dandona; Tufail Syed, M.D.,UB research assistant, and Arindam Bandyopadhyay, M.D. UB assistant professor of medicine, all from the Diabetes-Endocrine Center of Western New York at Kaleida Health.