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Drug Aimed at Treating Root Cause of Diabetes Might Help At-Risk Amputees

Type 2 diabetes affects an estimated 28 million Americans, according to the American Diabetes Association, but current medications only treat symptoms, not the root cause of the disease. New research from Rutgers University shows promising evidence that a modified form of a different drug, niclosamide-now used to eliminate intestinal parasites-may hold the key to battling the disease at its source.

The study, led by Victor Shengkan Jin, PhD, an associate professor of pharmacology at Rutgers Robert Wood Johnson Medical School, has been published online by the journal Nature Medicine.

Jin said it is important to find a suitable medication to correct the cause of the disease as quickly as possible because the only way now known to “cure” the disease involves major gastric bypass surgery. “The surgery can only be performed on highly obese people,” Jin explained, “and carries significant risks that include death, so it is not a realistic solution for most patients.”

And the number of patients continues to rise. The Centers for Disease Control and Prevention projects that 40 percent of all Americans now alive will develop type 2 diabetes. Many amputees are also at an increased risk for the disease because of a sedentary lifestyle.

Type 2 is the form of diabetes once known as “adult onset,” in which the body produces insulin that ordinarily would keep blood sugar under control, but either it does not produce enough insulin or the body’s ability to use that insulin is degraded.

According to Jin, a major cause of insulin resistance is the accumulation of excess fat in the cells of the liver, as well as in muscle tissue. The fat disrupts the process where, ordinarily, insulin would cause body tissues to correctly absorb glucose-blood sugar-and use it as fuel.

With nowhere else to go, much of the excess glucose remains in the bloodstream, where in high concentrations it can damage tissues throughout the body-potentially leading to blindness, amputation, kidney damage, cardiovascular diseases, and other severe health problems.

“Our goal in this study was to find a safe and practical way of diminishing fat content in the liver. We used mice to perform proof-of-principle experiments in our laboratory,” Jin said. “We succeeded in removing fat, and that in turn improved the animals’ ability to use insulin correctly and reduce blood sugar.”

The modified medication-niclosamide ethanolamine salt (NEN)-burned the excess fat in liver cells.

“Without the interference of fat, you hope that sugar will then enter the cell normally,” Jin said.

Getting rid of the interference of fat in liver and muscle tissue is the key to restoring the cells’ ability to respond to insulin properly, which would allow the right amount of sugar to be taken up by cells and ultimately reverse the diabetes entirely. That outcome is far from certain, but Jin said the positive changes he saw in the mice are encouraging.

This article was adapted from information provided by Rutgers University.