January 2001

From University of North Carolina at Chapel Hill

Expert: diabetes treatments undergoing quiet revolution

CHAPEL HILL -- Between the 1950s and 1994, treatments for diabetes patients changed little, a leading physician says, but in the past five years, a quiet and highly beneficial revolution has taken place. Now patients can control their blood sugar levels far more precisely than in the past and dodge complications of the illness until late life.

"Pretty much every year since 1995 there's been a major to moderate advance in our drug treatment possibilities in diabetes," said Dr. John B. Buse, associate professor of medicine at the University of North Carolina at Chapel Hill School of Medicine.

"There also have been great improvements in the old treatments as well - better drug delivery systems for the old sulfonylureas, better insulin delivery systems, better glucose monitoring and a greater understanding of the most appropriate doses to give," Buse said. "So diabetes treatment in 2001 is about as different as it could be from 1994, and that creates certain opportunities and challenges."

The greatest opportunity is that now just about everyone's diabetes can be controlled, the physician said, but the therapies are expensive. Another challenge is that because most U.S. doctors finished their training before the advances occurred, many still are not yet up to date on them.

"Still another major challenge is that more than half the children who develop diabetes now have type 2, which classically developed in adults," he said. "Now, our children are often as overweight and sedentary as 50- and 60-year-old people of a generation ago. They are actually developing the middle-aged form of the disease."

Buse spoke Thursday (Jan. 18) at an American Medical Association briefing in New York at the New York Academy of Sciences. His talk, "New and Future Treatments of Hyperglycemia in Type 2 Diabetes," aimed to bring the new developments in diabetes care to the attention of other doctors and the general public.

"Recent clinical trials have shown that maintaining normal blood sugar can pay off in fewer complications," said the physician, who also directs UNC-CH's Diabetes Care Center. "Among these complications are heart disease, peripheral vascular disease, stroke, nerve damage, eye problems and kidney disease in both type 2 and type 1 diabetes."

Drug improvements include:
new sulfonylureas that stimulate the pancreas to produce more insulin.
metformin, which improves the liver's natural response to insulin, which is to prevent excessive sugar release into the blood.
alpha-glucosidase inhibitors, which function by slowing starch breakdown and thus delivery of sugars from the intestines to the bloodstream.
megitinides, fast-acting, sulfonylurea-like compounds that also stimulate natural insulin production.
thiazolidinediones, which are insulin sensitizers that allow insulin to be used more efficiently and promise to reduce heart risks associated with diabetes.

Insulin, generated by the pancreas in healthy people, supplements or replaces insulin in the blood to enable the body to metabolize sugars, Buse said. Its purpose is to signal the liver to stop making glucose. When insulin levels are low, the liver starts pumping glucose out and muscles and fat stop storing it so that the brain will get enough. When glucose levels fall, such as after exercise or not eating for prolonged periods, less insulin is needed.

"The body is really blind to what the level of glucose is, and so it needs the insulin signal to stop making glucose and to start storing it," he said. "The old techniques for artificial insulin delivery didn't allow us to match up things very well," he said. In type 1 diabetes, cells that make insulin are destroyed by a selective immune process. Treatment involves the best possible replacement of insulin production. New faster-acting insulin analogs created by recombinant DNA techniques behave more like the natural insulin that flows directly into the pancreas' portal vein and then throughout the body.

In type 2 diabetes two problems occur. One is that the body doesn't produce quite enough insulin, and the other is that the insulin that is generated doesn't work as well as it should in tissues that respond to it. Metformin improves the liver sensitivity to counteract that second problem, while other drugs boost production.

"The future of diabetes treatment is promising," Buse said. "This year we should get a new long-lasting insulin, a new short-acting insulin and several other drugs. The recent gains are just the beginning."

The scary thing is that 20 to 30 years after a diagnosis of diabetes "all kinds of bad things are happening to people," he said. "It makes perfect sense to me that we're not taking future diabetes seriously because there's no money in preventive health care. Food's getting cheaper and cheaper, and drugs are getting more expensive. We live in a crazy world."

Note: Buse can be reached at (919) 949-2126, via pager at 1-800-593-6916 or through the AMA's news department at (312) 464-5374. After returning to Chapel Hill, he can be reached at (919) 484-0931.











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