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Smoking, insulin resistance, and endothelial dysfunction

Institution: Stanford University
Investigator(s): Gerald Reaven, M.D.
Award Cycle: 2003 (Cycle 12) Grant #: 12RT-0159 Award: $814,989
Subject Area: Cardiovascular Disease
Award Type: Research Project Awards

Initial Award Abstract
Although it is well recognized that cardiovascular disease (CVD) is increased in cigarette smokers, the cause and effect relationship between smoking and CVD is not clear. The rationale behind this study is that cigarette smokers tend to be more resistant to the action of insulin than nonsmokers, and it is the subset of smokers that are the most insulin resistant, with its associated adverse consequences, that are the greatest risk of CVD. Furthermore, it is proposed that administration of pioglitazone (PIO), a drug that improves insulin sensitivity, will significantly decrease overall CVD risk when give to insulin resistant individuals, unwilling to stop smoking. In contrast, PIO treatment in the control group, insulin sensitive smokers unwilling to stop smoking, will have little, or no, effect on decreasing overall CVD risk.

During the first year of the study we have been successful in enrolling 17 cigarette smokers, unwilling to stop smoking, and have strong, but preliminary, evidence that PIO treatment is able to significantly enhance insulin sensitivity in insulin resistant smokers. We plan to continue to enroll subjects in both experimental groups, and evaluate the effects of PIO treatment on multiple CVD risk factors associated with smoking. If the preliminary results can be confirmed, it will provide a possible therapeutic approach to reduce CVD in individuals who are determined to continue smoking.