BACKGROUND: Previous studies have demonstrated that cardiovascular risk is higher with increased lipoprotein (a) [Lp(a)]. Whether Lp(a) concentration is related to type 2 diabetes is unclear. METHODS: In 26 746 healthy US women (mean age 54.6 years), we prospectively examined baseline Lp(a) concentrations and incident type 2 diabetes (n = 1670) for a follow-up period of 13 years. We confirmed our findings in 9652 Danish men and women with prevalent diabetes (n = 419). Analyses were adjusted for risk factors that included age, race, smoking, hormone use, family history, blood pressure, body mass index, hemoglobin A(1c) (Hb A(1c)), C-reactive protein, and lipids. RESULTS: Lp(a) was inversely associated with incident diabetes, with fully adjusted hazard ratios (HRs) and 95% CIs for quintiles 2-5 vs quintile 1 of 0.87 (0.75-1.01), 0.80 (0.68-0.93), 0.88 (0.76-1.02), and 0.78 (0.67-0.91); P for trend 0.002. The association was stronger in nonfasting women, for whom respective HRs were 0.79 (0.58-1.09), 0.78 (0.57-1.08), 0.66 (0.46-0.93), and 0.56 (0.40-0.80); P for trend 0.001; P for interaction with fasting status 0.002. When we used Lp(a) >= 10 mg/L and Hb A(1c) = 10 mg/L and Hb A(1c) 5%-