Lipoprotein(a) and risk of type 2 diabetes

Abstract

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.

Fig. 1

Cumulative probability of incident type 2 diabetes according to quintiles of Lp(a) concentration in the Women’s Health Study, stratified by nonfasting or fasting state at the time of the blood draw.

Fig. 2

Additive association of Lp(a) (mg/dL) and HbA_1c (%) concentrations with incident type 2 diabetes in the Women’s Health Study. Hazard ratios were adjusted for age, race, randomized treatment assignment, smoking status, menopausal status, postmenopausal hormone use, blood pressure, body mass index, family history of diabetes, high-sensitivity C-reactive protein, LDL cholesterol, HDL cholesterol, and triglycerides.