Context: Low plasma adiponectin concentrations in smokers may contribute to the adverse consequences that occur in these individuals.

Objective: To define the relationship between smoking, plasma adiponectin concentrations, insulin resistance, and inflammation.

Design: Cross-sectional, observational, 2 x 2 factorial with a prospective longitudinal arm.

Setting: General Clinical Research Center.

Participants: Apparently healthy smokers (n = 30) and nonsmokers (n = 30), subdivided into insulin resistant (IR) [n = 15] and insulin sensitive (IS) [n = 15] subgroups.

Intervention: Pioglitazone administration for three months to12 IR smokers and 8 IS smokers.

Main outcome measures: 1) Fasting plasma adiponectin and C-reactive protein (CRP) concentrations; 2) Changes in adiponectin following pioglitazone treatment in IR and IS smokers.

Results: Being either a smoker or having insulin resistance was independently associated with lower adiponectin concentrations (P values, 0.046 and 0.001, respectively). The difference in mean adiponectin concentration between smokers and nonsmokers did not depend on the insulin resistance status of the subjects. No difference was detected in average CRP concentrations between smokers and nonsmokers (P = 0.18) and between IR and IS subjects (P = 0.13). CRP concentrations were unrelated to adiponectin in smokers (r = -0.05, P = 0.78) and nonsmokers (r = 0.03, P = 0.86). Finally, pioglitazone treatment increased adiponectin concentrations in both IR (P < 0.001) and IS smokers (P = 0.001).

Conclusion: Plasma adiponectin concentrations are lower in smokers and IR subjects and are unrelated to increases in CRP concentration. These findings suggest that low levels of adiponectin in smokers may be independent of both insulin resistance and a generalized inflammatory response.