Weight gain and insulin resistance during nicotine replacement therapy

Background: Although the cessation of smoking reduces the increased risk fo r ischemic heart disease, it is associated with marked weight gain and pres umably insulin resistance, both of which heighten the risk of coronary hear t 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 se nsitivity was assessed by an insulin-enhanced, frequently sampled intraveno us glucose tolerance test with minimal model analysis. The subjects were st udied 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 (p hase 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 a 0.2 k g/week) (p = 0.3). Insulin sensitivity decreased by 14 +/- 2.6% luring nico tine replacement but increased by 16 +/- 5.1% (compared with phase 2) durin g 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 improveme nt in insulin resistance. Nicotine is the main ingredient in cigarette smok e causing insulin resistance, but the withdrawal of another, unknown ingred ient in cigarette smoke is responsible for the weight gain associated with smoking cessation.