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) > or =10 mg/L and Hb A(1c) <5% as reference values, the adjusted HRs were 1.62 (0.91-2.89) for Lp(a) <10 mg/L and Hb A(1c) <5%, 3.50 (3.06-4.01) for Lp(a) > or =10 mg/L and Hb A(1c) 5%-<6.5%, and 5.36 (4.00-7.19) for Lp(a) <10 mg/L and Hb A(1c) 5%-<6.5%. Results were similar in nonfasting Danish men and women, for whom adjusted odds ratios were 0.75 (0.55-1.03), 0.64 (0.46-0.88), 0.74 (0.54-1.01), and 0.58 (0.42-0.79) for Lp(a) quintiles 2-5 vs quintile 1; P for trend 0.002.
Conclusions: Our results indicated that Lp(a) was associated inversely with risk of type 2 diabetes independently of risk factors, in contrast to prior findings of positive associations of Lp(a) with cardiovascular risk.
Trial registration: ClinicalTrials.gov NCT00000479.