Researchers presented the study at the American Diabetes Association's 62nd Scientific Sessions.
"The study has important implications for treatment strategies to prevent type 2 diabetes. It also helps define the primary cause of the disease: the failure of insulin-secreting cells caused by high insulin demands when the body?s tissues become resistant to its own insulin," says Thomas A. Buchanan, M.D., professor of medicine, obstetrics and gynecology and physiology and biophysics at the Keck School and the study?s lead author.
The Troglitazone in Prevention of Diabetes (TRIPOD) study previously found that using a drug to lessen insulin resistance could reduce the demands on beta cells- which secrete insulin in response to glucose- and prevent or slow type 2 diabetes onset in Latinas with recent gestational diabetes.
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, Buchanan says. These women are considered at high risk for developing diabetes.
Buchanan and colleagues gave 121 young Latinas with recent gestational diabetes a daily dose of either troglitazone or a placebo. At that time, physicians nationwide commonly prescribed troglitazone to treat type 2 diabetes, because it helps the body's cells more effectively use insulin to absorb glucose. (The Food and Drug Administration recalled troglitazone in 2000, and USC researchers switched to prescribing pioglitazone, a similar-acting, FDA-approved drug in the ongoing study).
Any women in the placebo group who developed diabetes while participating in the study were switched to the anti-insulin-resistance drug. Thus, treatment in those women was begun later than in those who had taken the drug from the beginning of the study, before developing diabetes.
During the more than four years in which women were monitored, the group of 56 women who took the drug from the very start saw their insulin sensitivity and glucose tolerance tests remain stable. But among the 65 women who started on placebo, insulin sensitivity fell by 25 percent and acute insulin response fell by 39 percent. Glucose tolerance test levels rose by 10 percent, indicating growing levels of sugar in the blood.
When the researchers looked specifically at the group of women who originally received placebo, but were switched to troglitazone upon developing diabetes, they found that those women had an average decline in beta-cell function of 30 percent during the time they were developing diabetes while taking placebo. Once they developed diabetes and started taking the drug, the beta-cell decline stopped. Here is how it works:
When the body's muscle and fat cells grow resistant to insulin, the beta cells in the pancreas shift into overdrive to produce more insulin to compensate. Over time, this high workload causes beta cells to wear out in some people and produce less insulin, or stop altogether, causing type 2 diabetes. Buchanan and colleagues believe that lessening the workload might keep the beta cells from failing, thereby preventing diabetes. The results from this new analysis indicate that intervening early, before diabetes develops, saves about 30 percent more beta cells than can be saved if treatment is withheld until diabetes first develops.
Buchanan and colleagues are now furthering the research, seeking to understand why some peoples' beta cells wear out under high workloads, while others' do not.
Thomas Buchanan, Anny Xiang, Ruth Peters, Siri Kjos, Sylvia Tan, Aura Marroquin, Cesar Ochoa, Jose Goico and Stanley Azen, "Prevention of Type 2 Diabetes by Treatment of Insulin Resistance: Comparison of Early vs. Late Intervention in the TRIPOD Study," 62nd ADA Scientific Sessions, June 16. Category: Clinical Therapeutics. Abstract No. 140-OR.
TRIPOD lecture symposium on diabetes prevention, 10:15 a.m.-12:15 p.m. June 15, Moscone Center Rm. 305.