Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Clin Chem. 2010 Aug;56(8):1252-60. doi: 10.1373/clinchem.2010.146779. Epub 2010 May 28.
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.
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.
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.
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.
之前的研究表明，脂蛋白(a)[Lp(a)]升高与心血管风险增加有关。Lp(a)浓度与 2 型糖尿病之间的关系尚不清楚。
在 26746 名美国健康女性（平均年龄 54.6 岁）中，我们前瞻性地检查了基线 Lp(a)浓度和 13 年的 2 型糖尿病（n=1670）发病情况。我们在丹麦 9652 名有糖尿病病史的男性和女性（n=419）中证实了我们的发现。分析调整了包括年龄、种族、吸烟、激素使用、家族史、血压、体重指数、糖化血红蛋白（Hb A(1c)）、C 反应蛋白和脂质在内的危险因素。
Lp(a)与糖尿病发病呈负相关，第 2-5 五分位组与第 1 五分位组的调整后风险比（HR）和 95%置信区间（CI）分别为 0.87（0.75-1.01）、0.80（0.68-0.93）、0.88（0.76-1.02）和 0.78（0.67-0.91）；趋势 P 值为 0.002。在非禁食女性中，关联更强，相应的 HR 分别为 0.79（0.58-1.09）、0.78（0.57-1.08）、0.66（0.46-0.93）和 0.56（0.40-0.80）；趋势 P 值为 0.001；与禁食状态的交互作用 P 值为 0.002。当我们将 Lp(a)≥10mg/L 和 Hb A(1c)＜5%作为参考值时，Lp(a)＜10mg/L 和 Hb A(1c)＜5%的调整 HR 为 1.62（0.91-2.89），Lp(a)≥10mg/L 和 Hb A(1c)5%-＜6.5%的调整 HR 为 3.50（3.06-4.01），Lp(a)＜10mg/L 和 Hb A(1c)5%-＜6.5%的调整 HR 为 5.36（4.00-7.19）。在非禁食的丹麦男性和女性中也得到了相似的结果，Lp(a)第 2-5 五分位组与第 1 五分位组的调整比值比（OR）分别为 0.75（0.55-1.03）、0.64（0.46-0.88）、0.74（0.54-1.01）和 0.58（0.42-0.79）；趋势 P 值为 0.002。
我们的结果表明，Lp(a)与 2 型糖尿病风险呈负相关，独立于危险因素，与之前 Lp(a)与心血管风险呈正相关的发现相反。
