Smoking is associated with impaired glucose regulation and a decrease in insulin sensitivity and the disposition index in first-degree relatives of type 2 diabetes subjects independently of the presence of metabolic syndrome.

The aim of this study was to investigate glucose tolerance, insulin secretion and insulin resistance according to smoking habits in first-degree relatives of type 2 diabetes patients, a population at high risk for developing diabetes. One thousand three hundred (646 females and 654 males) subjects underwent an oral glucose tolerance test (OGTT) to investigate their glucose metabolism and answered questionnaires about their lifestyle habits. Smoker subjects showed significant impairment compared with non-smoker subjects in 2-h post-oral glucose tolerance test (2hOGTT, 129.3 ± 40.2 vs. 117.7 ± 37.6 mg/dl, p < 0.001), the OGTT insulin sensitivity (386.3 ± 54.9 vs. 400.5 ± 53.4 ml min(-1) m(2), p < 0.01) method and the insulin sensitivity and secretion index-2 (ISSI-2, 1.7 ± 0.8 vs. 2.0 ± 1.0, p < 0.005). Metabolic syndrome (MS) was higher in the smoker than in the non-smoker group (46.5 vs. 29.7 %, p < 0001), and smokers were more sedentary than non-smokers (3.94 ± 3.77 vs. 4.86 ± 4.41 h/week, p < 0.001). Smokers showed an increased risk of impaired glucose regulation (IGR: impaired glucose tolerance or diabetes mellitus) with a hazard ratio (HR) adjusted by gender, metabolic syndrome and physical activity of 1.78, 95 % CI 1.27-2.47 (p < 0.001). The association between smoking and MS conferred a risk of IGR that was five times higher (HR 5.495, 95 % CI 4.07-7.41, p < 0.001). Smoking habit was a significant explanatory variable in a multiple forward stepwise regression analysis performed using 2hOGTT and ISSI-2 as dependent variables (p < 0.0001, R = 0.313 and p < 0.0001, R = 0.347, respectively). In conclusions, our results show that tobacco smoking is tightly associated with impairments in glucose metabolism and insulin sensitivity and insulin secretion.