Background and objectives To evaluate the association between high levels of glycemia and low serum uric acid levels in two independent population-based samples. Patients and methods The first sample was taken from the Pizarra Study, a population-based prospective study of 1.226 persons classified according to their glycometabolic status, as measured from an oral glucose tolerance test. Variables recorded included anthropometric data, serum fasting insulin, uric acid (UA) and HOMA-IR. The second sample was obtained from the Central Laboratory Database, which includes 81,754 laboratory requests for HbA 1c carried out over 30 months. We selected those that included measurements of UA, triglycerides and albuminuria. Results In the Pizarra Study, the fasting glucose levels showed a bell-shaped relation with serum UA levels in men and more especially in women (P < 0.0001). In the second sample, the UA levels in women showed a bell-shaped relation with HbA 1c, increasing as the HbA 1c rose to 7% and then falling with the further increase of HbA 1c (P < 0.0001). Men experienced a linear decrease in UA levels as the HbA 1c rose (r = −0.19; P < 0.0001), though only with effect from HbA 1c values > 7%. The odds ratio for hyperuricemia (≥ 6 mg/dL in women and ≥ 7 mg/dL in men) fell continuously as the HbA 1c levels rose. Conclusions This study, undertaken in two different populations, showed that serum UA levels are non-linearly correlated with the levels of glucose, HbA 1c and HOMA-IR, especially in women. The risk of hyperuricemia and gout may be higher in persons with prediabetic states or with better-controlled diabetes than in persons with poorly-controlled diabetes.