Drugs Show Promise as Treatment for Diabetes

United Press International

A new class of drugs is showing promise for treating and possibly preventing one of the most common and serious complications of diabetes that can lead to amputations.

Known as aldose reductase inhibitors, the drugs may be effective in treating diabetic neuropathy, a deterioration of nerve fibers that causes a variety of nervous system symptoms.

As many as 1 million of the 10 million diabetic Americans experience severe diabetic neuropathy. Symptoms include a loss of coordination and sensation in various parts of the body. The loss of sensation can become so severe that victims break bones or damage the skin on their feet to the point where amputation is necessary.

The cause of the condition is unknown. But researchers believe chronic high levels of sugar in the blood may lead to the damaging accumulation of certain types of sugars on nerve fibers.


Researchers speculate that an enzyme, aldose reductase, converts blood sugar into another form of sugar, known as sorbitol, which accumulates on and damages the nerve fibers.

That has led several drug companies to begin testing agents that inhibit the enzyme in the hopes that it will prevent the accumulation of the sugar and the resulting damage.

Two studies published recently in the New England Journal of Medicine provide new evidence that the approach may work.

“I think this is the first evidence that this disease is actually potentially reversible,” said Dr. Douglas Greene, head of one of the studies and professor of internal medicine at the University of Michigan medical school in Ann Arbor.


In Greene’s study, 10 diabetics were given an aldose reductase inhibitor known as Sorbinil for one year. The researchers took samples of a nerve behind their ankles before they began treatment and after 12 months. The samples were compared to those taken from six diabetics who did not take the drug.

The researchers reported that patients who took the drug had about a 25% increase in the number of nerve fibers, and the regeneration of nerves was increased by about four times compared to those who did not take the drug.

Although the patients did show some signs of a decrease in symptoms, another larger study involving the same patients and others aimed at gauging symptoms had not yet been analyzed, Greene said.

But the findings indicate that the drug should be effective for treating diabetic neuropathy and may also succeed in preventing the condition, Greene said.

“I think it gives a lot of hope to people with diabetes,” said Greene in a telephone interview. “If this drug can reverse this disease this late in the game, it gives a lot of hope.”

Although none of the patients in the study experienced any significant side effects, previous research indicates that one in every 10 diabetics may have adverse reactions to the drug, such as a severe rash, Greene noted.

In the second study, researchers at the Mayo Clinic in Rochester, Minn., found that six diabetics who received the drug for a year had lower levels of sorbitol accumulations.

In an editorial accompanying the studies, Dr. Arthur Asbury of the University of Pennsylvania in Philadelphia said the findings “must be interpreted cautiously” but raise hope that the drugs will be effective.


But both Asbury and other researchers said the study must be duplicated with larger numbers of patients. “The preliminary indications are that this class of drugs may be effective,” Asbury added in a telephone interview. “But the data isn’t in yet.”

Two other aldose reductase inhibitors, tolrestat and statil, appear less likely to cause side effects. But there has yet to be any definitive evidence of their effectiveness, he said.

Dr. Gordon Weir, medical director of the Joslin Diabetes Center in Boston, said the findings in the new studies were encouraging that this type of drug may prove effective.

But he cautioned that small studies evaluating the effectiveness of Sorbinil on alleviating actual symptoms have been disappointing.

“The general approach seems to be promising,” said Weir. “But this particular drug does not seem to be a magical drug for people who are suffering from neuropathy. There may be better drugs.”