Preventing Type 2 Diabetes
Can drugs prevent the onset of type 2 diabetes? One class of drugs shows promise, but it has its drawbacks.
TZDs and the TRIPOD Study continued...
The pancreatic cells respond by producing more insulin to make up for this resistance. While the beta cells may be able to produce enough insulin to keep blood glucose at normal levels for a time, the increased production of insulin eventually may take a toll. The beta cells may become compromised and their ability to produce insulin will diminish, causing insulin deficiency. The body will become less capable of processing blood sugar, blood sugar levels will rise, and type 2 diabetes can follow. About 70 to 80 million Americans are estimated to have insulin-resistance syndrome and 17 million have type 2 diabetes.
Buchanan believes that TZDs might prevent beta cells from becoming overloaded and wearing out. By averting this, insulin resistance wouldn't worsen and, by extension, the development of type 2 diabetes could be stopped.
In the TRIPOD study, 235 Hispanic women who previously had gestational diabetes -- diabetes that develops during pregnancy -- and were at high risk of developing type 2 diabetes were treated with the TZD Rezulin (troglitazone), then another TZD, Actos. Buchanan and his colleagues found that the TZDs stabilized beta-cell function and led to a 55% reduction in diabetes compared with a placebo group. Startlingly, the benefits of the drugs seemed to last even after use was stopped.
"That was one of the most striking results," Buchanan tells WebMD. "We found that in people who didn't have diabetes, the preventative effect of the drug persisted eight months after it was stopped."
The Technical Details: How TZDs Work
The exact mechanism of how TZDs improve beta-cell function isn't entirely understood. The most widely accepted theory is that TZDs activate a receptor common in fat cells called the nuclear peroxisomal proliferator-activated receptors-gamma, or PPAR-gamma. These receptors affect how glucose and fats are metabolized, and once they are activated, the uptake or absorption of fat cells is increased; this also stimulates the 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 abdomen -- seems to be connected to the development of insulin resistance while subcutaneous fat -- fat beneath the skin in other parts of the body -- is not. TZDs appear to decrease the amount of visceral fat and increase the amounts of subcutaneous fat.