Weight gain and insulin resistance during nicotine replacement therapy

Background: Although the cessation of smoking reduces the increased risk for ischemic heart disease, it is associated with marked weight gain and presumably insulin resistance, both of which heighten the risk of coronary heart disease. Hypothesis: We investigated the isolated effect of nicotine on body weight and insulin resistance during smoking cessation. Methods: Eleven healthy, middle-aged heavy smokers were studied. Insulin sensitivity was assessed by an insulin-enhanced, frequently sampled intravenous glucose tolerance test with minimal model analysis. The subjects were studied at baseline (last day of smoking) (phase 1), at the end of the 6-week nicotine replacement program (phase 2), and after 8 weeks without smoking or nicotine replacement (phase 3). Results: The subjects started to gain weight during nicotine replacement (phase 2) (0.3 ± 0.2 kg/week, mean ± standard deviation) and continued to do so at a steady rate after nicotine replacement was stopped (0.2 ± 0.2 kg/week) (p = 0.3). Insulin sensitivity decreased by 14 ± 2.6% during nicotine replacement but increased by 16 ± 5.1% (compared with phase 2) during phase 3, even though the weight gain continued (p = 0.047; 95% confidence interval: 0.05-5.73). Conclusions: Smoking cessation is associated with weight gain and improvement in insulin resistance. Nicotine is the main ingredient in cigarette smoke causing insulin resistance, but the withdrawal of another, unknown ingredient in cigarette smoke is responsible for the weight gain associated with smoking cessation.