Division of Cardiology, University of Colorado School of Medicine, Aurora, CO
Division of Cardiology, University of Colorado School of Medicine, Aurora, CO.
Diabetes Care. 2021 May;44(5):1219-1227. doi: 10.2337/dc20-2842. Epub 2021 Mar 15.
In observational data, lower levels of lipoprotein(a) have been associated with greater prevalence of type 2 diabetes. Whether pharmacologic lowering of lipoprotein(a) influences incident type 2 diabetes is unknown. We determined the relationship of lipoprotein(a) concentration with incident type 2 diabetes and effects of treatment with alirocumab, a PCSK9 inhibitor.
In the ODYSSEY OUTCOMES trial alirocumab was compared with placebo in patients with acute coronary syndrome. Incident diabetes was determined from laboratory, medication, and adverse event data.
Among 13,480 patients without diabetes at baseline, 1,324 developed type 2 diabetes over a median 2.7 years. Median baseline lipoprotein(a) was 21.9 mg/dL. With placebo, 10 mg/dL lower baseline lipoprotein(a) was associated with hazard ratio 1.04 (95% CI 1.02-1.06, < 0.001) for incident type 2 diabetes. Alirocumab reduced lipoprotein(a) by a median 23.2% with greater absolute reductions from higher baseline levels and no overall effect on incident type 2 diabetes (hazard ratio 0.95, 95% CI 0.85-1.05). At low baseline lipoprotein(a) levels, alirocumab tended to reduce incident type 2 diabetes, while at high baseline lipoprotein(a) alirocumab tended to increase incident type 2 diabetes compared with placebo (treatment-baseline lipoprotein(a) interaction = 0.006). In the alirocumab group, a 10 mg/dL decrease in lipoprotein(a) from baseline was associated with hazard ratio 1.07 (95% CI 1.03-1.12; = 0.0002) for incident type 2 diabetes.
In patients with acute coronary syndrome, baseline lipoprotein(a) concentration associated inversely with incident type 2 diabetes. Alirocumab had neutral overall effect on incident type 2 diabetes. However, treatment-related reductions in lipoprotein(a), more pronounced from high baseline levels, were associated with increased risk of incident type 2 diabetes. Whether these findings pertain to other therapies that reduce lipoprotein(a) is undetermined.
在观察性数据中，脂蛋白(a)水平较低与 2 型糖尿病的患病率较高有关。降低脂蛋白(a)的药物治疗是否会影响 2 型糖尿病的发生尚不清楚。我们确定了脂蛋白(a)浓度与 2 型糖尿病发病的关系，以及使用 PCSK9 抑制剂阿利西尤单抗的治疗效果。
在 ODYSSEY OUTCOMES 试验中，阿利西尤单抗与安慰剂在急性冠状动脉综合征患者中进行了比较。通过实验室、药物和不良事件数据确定新发糖尿病。
在基线时无糖尿病的 13480 名患者中，中位数为 2.7 年的期间内，有 1324 人发生 2 型糖尿病。中位基线脂蛋白(a)为 21.9mg/dL。与安慰剂相比，基线脂蛋白(a)每降低 10mg/dL，2 型糖尿病发病的风险比为 1.04（95%CI，1.02-1.06，<0.001）。阿利西尤单抗使脂蛋白(a)中位数降低 23.2%，基线水平较高时绝对降低幅度更大，但对 2 型糖尿病的发病无总体影响（风险比 0.95，95%CI，0.85-1.05）。在低基线脂蛋白(a)水平时，阿利西尤单抗倾向于降低 2 型糖尿病的发病，而在高基线脂蛋白(a)水平时，阿利西尤单抗与安慰剂相比，倾向于增加 2 型糖尿病的发病（治疗-基线脂蛋白(a)交互作用=0.006）。在阿利西尤单抗组中，与基线相比，脂蛋白(a)降低 10mg/dL，2 型糖尿病发病的风险比为 1.07（95%CI，1.03-1.12；=0.0002）。
在急性冠状动脉综合征患者中，基线脂蛋白(a)浓度与 2 型糖尿病的发病呈负相关。阿利西尤单抗对 2 型糖尿病的总体发病效果呈中性。然而，与治疗相关的脂蛋白(a)降低，在基线水平较高时更为明显，与 2 型糖尿病发病风险增加相关。这些发现是否适用于其他降低脂蛋白(a)的治疗方法尚不确定。
