ObjectiveTo stop smoking is commonly associated with significant weight gain, but the mechanisms for this are poorly understood. We assessed the effects of smoking cessation on body weight, insulin sensitivity, β-cell function, and appetite.Subjects and methodsTwenty-seven long-term smokers (n=27; nine females/18 males, 28±1 years, 22.9±0.6 kg/m2) attending an ambulatory smoking cessation program in a community hospital in Vienna, Austria were examined at baseline (Visit A; still smoking) and after a minimum of 3 months of smoking abstinence (Visit B;n=14); relapsed smokers were not followed up. Participants underwent 3-h oral glucose tolerance tests and body composition measurements at each study visit. Fasting (QUICKI) and dynamic (oral glucose insulin sensitivity (OGIS)) insulin sensitivity and β-cell secretion (insulinogenic index 140 (IGI40)) were calculated. Food intake was quantified with a free choice buffet. Fasting plasma concentrations of neuropeptide-Y (NPY), peptide-YY (PYY), glucagon-like peptide 1 (GLP1), leptin, ghrelin, and visfatin were measured.ResultsAfter >3 months' smoking abstinence, body weight, and fat mass were increased (+4 and +22% respectively,PP3 months' smoking abstinence (PP3 months (PConclusionSmoking cessation is associated with transient metabolic changes including increased β-cell secretion in response to glucose and fasting insulin resistance. These alterations may be associated with or contribute to the body weight gain after smoking cessation.