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
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
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