Issue 128 Item 11 Treating Pre-Diabetes Saves Beta Cells and Prevents Type 2 Dia

"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," said Thomas A. Buchanan, M.D., of Keck School of Medicine, University of California.

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 produce 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 percent to 50 percent develop type 2 diabetes within a few years after pregnancy, Buchanan said. These women are considered at high risk for developing diabetes.

The researchers randomly assigned 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 the researchers switched to prescribing pioglitazone, a similar-acting drug, in the ongoing study.

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.

The researchers are now seeking to understand why some peoples' beta cells wear out under high workloads, while others' do not.