Background: Elevated serum uric acid has been related to insulin resistance, but there are no studies regarding its association with beta-cell function. In this study, we examine the response of beta-cell function to compensate insulin resistance in hyperuricaemic subjects. Methods: Population-based cross-sectional study. A total of 212 healthy individuals, men and non-pregnant women, aged 20-65 years, were randomly recruited and allocated into groups with hyperuricaemia or normouricaemia that were matched by value of Belfiore index. Hyperuricaemia was defined by serum uric acid concentration >or=416 micromol/L in men and >or=357 micromol/L in women. To evaluate the compensation of insulin secretion to variation of insulin sensitivity, we used a surrogate of the hyperbolic model of beta-cell function based on Belfiore and Homeostasis Model Analysis beta-cell (HOMA-ss) indexes; the area under curves (AUC) was calculated. The association between the uric acid levels and the AUC was estimated using a multivariate regression analysis adjusted by age, sex, and waist circumference. Results: Hyperuricaemia was identified in 77 (36.3%) individuals. A total of 39 (50.6%) hyperuricaemic and 44 (32.6%) normouricaemic subjects had diagnosis of impaired glucose tolerance (IGT), p = 0.01. In the total population, the AUCs in the hyperuricaemic and normouricaemic groups were 1.60725 cm(2) and 3.9819 cm(2), respectively (odds ratio [OR] 3.9; CI 95% 1.4-8.9). Among the 83 individuals with IGT, the AUCs in the subgroups with and without hyperuricaemia were 0.8495 cm(2) and 2.42075 cm(2), respectively (OR 2.7; CI 95% 1.3-10.1). Conclusions: Our results show the failure of beta-cell function to compensate variation of insulin sensitivity in the hyperuricaemic individuals.