Pioglitazone administration decreases cardiovascular disease risk factors in insulin-resistant smokers

Abstract

Insulin sensitivity varies in cigarette smokers, and there is evidence that cardiovascular disease (CVD) risk is greatest in those smokers who are also insulin resistant. To extend these observations, we sought to (1) compare CVD risk factors in smokers who do not plan to stop smoking, divided into insulin-resistant (IR) and insulin-sensitive (IS) subgroups, and (2) evaluate the ability of drug-induced changes in insulin sensitivity to decrease CVD risk. Thirty-six cigarette smokers were divided into IR (n = 19) and IS (n = 17) subgroups by determining their steady-state plasma glucose (SSPG) concentrations during the insulin suppression test (the higher the SSPG, the more insulin resistant the individual). In addition, baseline measurements were made of fasting lipid and lipoprotein concentrations; inflammatory markers; and daylong glucose, insulin, and free fatty acid responses to test meals. All subjects were treated with pioglitazone for 12 weeks, after which all baseline measurements were repeated. Baseline triglyceride and high-density lipoprotein cholesterol concentrations were significantly different in IR as compared with IS smokers ( P < .05) both before and after adjustment for differences in sex and body mass index. After pioglitazone treatment, SSPG concentration significantly fell in the IR smokers ( P < .001), associated with a significant improvement in the atherogenic lipoprotein profile seen at baseline ( P ≤ .03) and a decrease in soluble intercellular adhesion molecule 1 and C-reactive protein concentrations ( P = .01 and .02, respectively), whereas the IS smokers only had a significant increase in high-density lipoprotein cholesterol ( P = .004) and a decrease in soluble intercellular adhesion molecule 1 ( P = .02) and CRP ( P = .07) levels. In conclusion, cigarette smokers have profound differences in CVD risk factors related to their degree of insulin sensitivity. It is suggested that, in addition to smoking cessation efforts, attention should be given to identifying the subgroup of smokers most at risk for CVD, but unwilling or unable to stop smoking, and to initiating appropriate therapeutic interventions to decrease CVD in this high-risk group.