Insulin-resistance-fighting drug continues to protect against type 2 diabetes

USC study finds pioglitazone deters diabetes in women at high risk

NEW ORLEANS (June 17)- Administering a commonly available drug to lower insulin resistance in women who are at high risk for type 2 diabetes appears to prevent onset of the disease, according to a study by researchers at the Keck School of Medicine of the Univesity of Southern California presented at the American Diabetes Association’s 63rd Annual Scientific Sessions today.

The Pioglitazone in Prevention of Diabetes (PIPOD) study tested whether piglitazone could continue protecting women from diabetes just as troglitazone had done in the researchers’ prior study, TRIPOD. Both drugs appear to reduce the demands placed on beta cells, which must secrete large amounts of insulin to regulate glucose when patients become insulin resistant. The researchers switched to prescribing pioglitazone, known by the brand name Actos, after the Food and Drug Administration recalled troglitazone in 2000.

Although gestational diabetes usually disappears after childbirth, patients commonly remain resistant to their own insulin, and 30 to 50 percent of them develop type 2 diabetes within a few years after pregnancy, says Anny H. Xiang, Ph.D., assistant professor of research in preventive medicine at the Keck School of Medicine and study presenter.

For this study, Xiang and colleagues enrolled 117 young Latinas with recent gestational diabetes who had participated in their prior TRIPOD study. TRIPOD had found that women taking troglitazone were 55 percent less likely to develop diabetes than women who got a placebo, and their glucose levels remained stable for nearly five years. All 117 women in PIPOD were given pioglitazone.

Researchers now report that out of 76 PIPOD participants who started PIPOD without diabetes and who had an oral glucose tolerance test after being on pioglitazone for a year, only one woman (about 1 percent) developed diabetes. And of the 26 women who started PIPOD with mild diabetes, only nine still had a diabetic glucose level after a year.

The 46 women in PIPOD who had taken troglitazone during TRIPOD saw their blood sugar and insulin levels reduced by about the same amount during the first year of both studies. And the 56 women on placebo during the first study saw their glucose and insulin levels fall significantly during PIPOD compared to their levels in the first year of TRIPOD.

“So, the protection from diabetes that we saw in TRIPOD persisted during the first year of PIPOD,” says Thomas A. Buchanan, M.D., professor of medicine, obstetrics and gynecology and physiology and biophysics at the Keck School and a study author. “And starting pioglitazone treatment in women who were on placebo during TRIPOD lowered blood sugar and insulin levels appears to be protecting them against diabetes as well.”

Here is how it works: Beta cells, located in the pancreas, produce insulin in response to glucose, and they are the primary regulators of blood sugar. When they are overloaded over time, through the condition called insulin resistance, they begin to wear out. Their failure leads to diabetes.

Pioglitazone reduces chronic insulin resistance’s demands on beta cells. It does this by increasing the body’s sensitivity to insulin. With lower demands, beta cells do not fail as fast, and, in some patients, do not fail at all. When beta cells do not fail, patients do not get diabetes. Researchers will continue following the women for three more years to better understand protective effects.

The next question: Why do some people’s beta cells fail under a high workload, while other people’s beta cells do just fine?

Xiang, Buchanan and colleagues suspect genes are to blame. They are looking at families of women with gestational diabetes to see if their siblings have the same basic problem with their beta cells. They seek to identify genes that could contribute to diabetes risk among Mexican-Americans.

Collaborator Richard Watanabe, Ph.D., assistant professor of preventive medicine at the Keck School, reported at the meeting that the level of beta-cell function tends to run in families, as does (but to a lesser extent) the tendency to become insulin resistant. The finding underpins a large, family-based study to find genes predisposing Latinos to beta-cell problems leading to diabetes.

For abstracts and information about the meeting, go to

Anny H. Xiang, Ruth K. Peters, Siri L. Kjos, Jose Goico, Auro Marroquin, Cesar Ochoa, Sylvia Tan and Thomas A. Buchanan, “Continued Protection from Diabetes during Treatment of the TRIPOD Cohort with Pioglitazone,” American Diabetes Association’s 63rd Annual Scientific Sessions, Oral Presentation 322 in Treatment of Insulin Resistance session, 8 a.m. – 10 a.m., June 17, 2003.

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