Diabetes medication produces unexpected benefits

August 1, 1997

A new drug, currently being tested as a way to help persons at risk prevent or delay the onset of diabetes, has more beneficial effects than anticipated, reveals a study from the University of Chicago Medical Center. Troglitazone (trade name Rezulin) not only helped "pre-diabetic" patients use glucose efficiently, butalso enabled them to produce more insulin.

The finding, published in the August issue of the Journal of Clinical Investigation, suggests that troglitazone may play "an even larger than anticipated role in our efforts to prevent the development of diabetes in those who are most at risk," said Kenneth Polonsky, MD, professor of medicine and chief of endocrinology at the University of Chicago Medical Center.

The Diabetes Prevention Program, a multi-centered, seven-year trial begun in June 1996, is currently enrolling thousands of pre-diabetic volunteers to try to determine whether either of two medications, troglitazone or metformin, or a rigorous program of weight loss, diet and exercise can prevent diabetes.

This encouraging finding reinforces the prospects for a medication-based approach. "Although diet and exercise can have a dramatic impact," said Dr. Polonsky, "most people find it very difficult to maintain long-term lifestyle alterations, so a medication that could help prevent this devastating disease might have considerable impact."

In type-2 diabetes, also known as non-insulin-dependent diabetes mellitus (NIDDM), the body either cannot produce enough insulin or does not use it effectively. If this goes untreated, glucose-a form of sugar-accumulates in the blood stream, slowly damaging the cardiovascular system, kidneys, eyes, and nerves.

NIDDM affects 15 million people in the United States where it is the seventh leading cause of death, the leading cause of blindness, kidney failure and foot and leg amputations in adults. In the United States, the direct costs of medical care for people with NIDDM exceed $45 billion, with an additional $47 billion lost to disability and premature death. Nearly 2,000 new cases are diagnosed every day, a total of 625,000 each year. An estimated 2,000 new cases a day go undiagnosed.

Eleven percent of the U.S. adult population is "pre-diabetic." They have impaired glucose tolerance, in which blood sugar levels are higher than normal but not high enough to be classified as diabetes. The elevation is caused by insulin resistance (decreased ability of the body to respond to insulin) and by decreased insulin production by the pancreas. Seven percent of this group will develop diabetes each year.

In this small but carefully controlled study, 14 participants with IGT received oral troglitazone once a day for 12 weeks; seven similar participants received a placebo (an inactive pill).

After 12 weeks, those who received troglitazone showed dramatic improvements in blood-sugar levels. As expected, the insulin they secreted was more effective at controlling glucose. And insulin secretion increased by an average of 52 percent, the first time this has been documented in humans. Participants who receive troglitazone also had more normal responses to fluctuations in glucose, producing bursts of insulin in response to infusion of glucose. No improvements of insulin action or secretion were seen in the placebo group.

Although insulin secretion remained below normal, the combination of increased secretion and decreased insulin resistance "suggest that administration of troglitazone to subjects with impaired glucose tolerance may arrest or slow the mechanisms that underlie the progression from impaired glucose tolerance to frank diabetes," conclude the authors.

Additional authors of the paper include Melissa Cavaghan, David Ehrmann and Maria Byrne, department of medicine, University of Chicago. The research was sponsored by grants from the National Institutes of Health.

Summary:
A new drug currently being tested as a way to help persons at risk prevent or delay the onset of diabetes has more beneficial effects than anticipated reveals a study from the University of Chicago Medical Center. Troglitazone not only helped "pre-diabetic" patients use glucose efficiently, but also enabled them to produce more insulin.

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