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Aims: Cholecystectomy is a risk factor for insulin resistance and diabetes, but the association between cholecystectomy and insulin release/sensitivity remains obscure. We investigated the association between cholecystectomy and the factors related to glycemia and glucose tolerance.Methods: A cross-sectional study was conducted in 2011 with 10,027 participants aged ≥40 in Nanjing, China. After applying exclusion criteria, 8,030 participants were divided into three groups: 1, without gallbladder disease (n = 6783); 2, with gallbladder disease but without cholecystectomy (n = 857); and 3, with cholecystectomy (n = 390).Results: Various indexes of blood glucose and insulin level after the oral glucose tolerance test (OGTT) were assessed. The association between gallbladder disease or cholecystectomy and diabetes was evaluated with logistic regression models. Group 3 had a higher prevalence of newly diagnosed diabetes by OGTT criteria compared with groups 2 and 1, respectively (20.5% vs. 12.4% vs. 10.6%, P < 0.001). The adjusted odds ratio and 95% confidence interval of diabetes associated with cholecystectomy were 1.546 (1.168, 2.046) (P = 0.002). Pattern 2, which was characterized by a lasting late insulin response, was more frequent in group 3 compared with groups 2 and 1, respectively (61.0% vs. 54.3% vs.48.3%, P < 0.001). After adjusting for confounding factors, a higher total insulin release and lower Matsuda insulin sensitivity index (P < 0.001) were found in group 3 compared with the other two groups.Conclusions: Cholecystectomized subjects demonstrated a higher prevalence of diabetes characterized by lower peripheral insulin sensitivity and higher total insulin release. [ABSTRACT FROM AUTHOR]