Pioglitazone Prevents Restenosis in Diabetes by Reducing Leptin

Treating type 2 diabetes patients with pioglitazone after coronary stenting reduces restenosis.

The drug appears to exert its effects by reducing leptin levels, which in turn reduced insulin resistance and improved endothelial function.

Insulin resistance has recently been shown to predict early restenosis after stenting, Dr. Kazuaki Nishio of Showa University in Tokyo and colleagues note in the January issue of Diabetes Care. But the effectiveness of thiazolidinediones in preventing in-stent restenosis, they add, "remains controversial."

The researchers randomized 54 patients who underwent coronary stenting to 30 mg pioglitazone daily or placebo. All patients had homeostasis model of insulin resistance (HOMA-IR) above 2.

At six months, the researchers found, HOMA-IR was significantly reduced in patients on the drug, from 5.75 to 1.95, but was not significantly changed in those on placebo. Endothelial nitric oxide synthase fell from 25.7 to 14.4 pg/ml in the pioglitazone group, while it did not change in the placebo group. And leptin levels dropped from15.6 to 4.2 ng/ml in the drug group, but again did not change significantly in the control group.

Restenosis was 2% in patients on pioglitazone and 16% on control patients, while late luminal loss was 0.30 mm vs. 1.43 mm in patients on placebo.

Multiple regression analysis found an independent correlation between leptin levels and late luminal loss.

Given that not all patients with type 2 diabetes are insulin resistant, Dr. Nishio and colleagues note, it is possible that pioglitazone is only effective in preventing restenosis in patients with insulin resistance. Mixed results in past studies, they add, may have been due to the inclusion of non-insulin-resistant patients.

Diabetes Care 2006;29:101-106.

===============================

FACT: Chicago Named Fattest U.S. City: Baltimore has been named the fittest city in America by Men’s Fitness magazine, and Chicago has been named the fattest. Men’s Fitness magazine is out with its admittedly unscientific ranking of urban fitness and it puts Baltimore at the top, partly because of its parks, health care and air quality. But it’s also known as a place whose citizens like drinking and greasy foods. For the second year in a row, Honolulu ranks number two on the fit-cities list. Last year’s winner, Seattle, comes in eighth.