Preventing Type 2 Diabetes With TZDs

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The traditional medical approach to diabetes is simply to manage it after it has been diagnosed. Because there isn’t a cure, the emphasis is on keeping metabolism of glucose and lessens the liver’s production of new glucose.

What’s particularly interesting is that TZDs may actually increase the total amount of fat on a person, but they appear to cause a redistribution of fat in ways that may help increase insulin sensitivity. Visceral fat — fat surrounding the organs of the metformin [standard diabetes drugs].” Nathan tells WebMD the greatest benefit may come by combining TZDs with other drugs, although he cautions that the results of doing so are not yet fully understood.

Another potentially significant benefit of TZDs is that they appear to lower the levels of free fatty acids in the bloodstream, a new focus of attention for diabetes experts because of their connection to diabetic complications. “I think that’s an important aspect of TZDs,” says Paul Jellinger, MD, past president of the American Association of Clinical Endocrinologists. “It’s one of the apparent benefits of TZDs that hasn’t been widely appreciated yet.”

A New Direction?

Based in part on the results of the TRIPOD study, Buchanan believes the emphasis of diabetes treatment needs to be shifted.

“Basically, right now, we treat people whose glucose levels are already high enough to cause long-term complications and we try to get their levels lowered,” he says. “But by the time someone has gotten to the point of diabetes, they’ve probably lost about 80% of their beta-cell function. Someone with just Impaired glucose tolerance [an aspect of pre-diabetes] has already lost about 50% of their beta-cell function.”

Buchanan wants diabetics and doctors to understand better the difference between the manifestations of disease — heightened glucose levels — and the loss of beta-cell function that may be causing them.

“The current paradigm of diabetes treatment is focused on the sprint — what your glucose levels are — instead of the marathon, which is how the disease is progressing,” he says.

However, other experts caution that the results of the TRIPOD study and the effectiveness and safety of TZDs need to be confirmed.

“TZDs are an incredibly important addition to our set of tools,” says Fran Kaufman, president of the American Diabetes Association and division head of endocrinology at the Children’s Hospital Los Angeles. But she cautions that more studies need to be done. “Whether other studies will show a similarly robust effect of TZDs [as the TRIPOD study did] is something we just don’t know.”

The Risks and The Costs

There are potential dangers to TZDs. This was most evident in 2000, when the Food and Drug Administration asked the manufacturer of Rezulin to withdraw it after reports of severe and sometimes fatal edema — the build-up of fluid in tissue — from TZD use.

There have been reports of other potential problems, and one survey of patients using TZDs found that the risk of actually increased, in contrast to studies demonstrating the cardio-protective characteristics of the drugs.

Finally, the financial costs of TZDs may hamper their usefulness; they are significantly more expensive than other drugs used to treat diabetes. While Kaufman hopes that prices will drop as more TZDs are released, Buchanan is concerned that this may not happen until the patents on particular TZDs expire.

Who Needs TZDs?

Given the possible benefits of TZDs, you may wonder whether you should be using them yourself. They aren’t appropriate in all cases, and many of their benefits need to be confirmed.

For instance, despite the promise of the TRIPOD study, TZDs are not recommended for the treatment of pre-diabetes. “I get asked a lot whether you should treat everybody with insulin-resistance syndrome with a TZD,” says Buchanan, “and the answer is no.” Buchanan notes that insulin resistance is really marked by a cluster of things, and treatment should be based on what symptoms an individual has.

It is also crucial to know that other studies, such as the Diabetes Prevention Program (DPP), have demonstrated the effectiveness of behavioral interventions — such as regular exercise and weight loss — in slowing or preventing the progress of pre-diabetes to type 2 diabetes. Depending on your case, changes in your diet and an increase in exercise may be the best medicine.

For the time being, doctors are generally advised to use TZDs cautiously because of their potential risks. But the beneficial effects of TZDs point to a possible future in the treatment of diabetes.

“I think that if nothing else, TRIPOD showed that by focusing on the relieving the stress on beta cells, we can slow the progress of IGT and type 2 diabetes,” Buchanan says. “We can stabilize the process.”