Association of Lipoproteins, Insulin Resistance, and Rosuvastatin With Incident Type 2 Diabetes Mellitus : Secondary Analysis of a Randomized Clinical Trial.
Association of Lipoproteins, Insulin Resistance, and Rosuvastatin With Incident Type 2 Diabetes Mellitus : Secondary Analysis of a Randomized Clinical Trial.
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DOI：
10.1001/jamacardio.2016.0096
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发表时间：
2016-05-01
期刊：
影响因子：
24
通讯作者：
Mora S
中科院分区：
文献类型：
--
作者：
Dugani SB;Akinkuolie AO;Paynter N;Glynn RJ;Ridker PM;Mora S
他汀类药物降低低密度脂蛋白、甘油三酯和心血管事件，但增加被诊断为糖尿病的风险。与糖尿病发病相关的危险因素尚未完全确定。在随机接受高强度他汀类药物或安慰剂治疗的个体中，研究脂蛋白亚类和大小以及新型脂蛋白胰岛素抵抗（LPIR）评分（6种脂蛋白测量的复合物）与糖尿病发病率的相关性。JUPITER是一项国际、随机、双盲、安慰剂对照试验。预先设定的次要目的是评估瑞舒伐他汀对糖尿病的影响，并对糖尿病事件进行中位监测2.0年。该研究在26个国家的1315个研究中心进行。JUPITER纳入了17802例LDL胆固醇<130 mg/dL、hsCRP ≥2 mg/L和甘油三酯<500 mg/dL的男性≥50岁和女性≥60岁。糖尿病患者被排除。瑞舒伐他汀，每日20 mg，或安慰剂。在JUPITER的11918名参与者中，我们测量了基线脂质、载脂蛋白和脂蛋白的大小和浓度，其中9180名在随机分配至瑞舒伐他汀或安慰剂后12个月测量。LPIR评分（与胰岛素抵抗相关）计算为LDL、极低密度脂蛋白（VLDL）和高密度脂蛋白（HDL）颗粒大小和浓度的加权组合。瑞舒伐他汀降低了LDL颗粒（−49%）、VLDL颗粒（−20%）和甘油三酯（−15%），并使脂蛋白亚类分布向LDL尺寸较小（−2%）、VLDL尺寸较大（3%）和LPIR评分较低（−3%）的方向偏移。在校正了年龄、性别、种族/民族、运动、教育、家族史和吸烟的分析中，安慰剂组和瑞舒伐他汀组的糖尿病风险比（LPIR评分标准差）分别为1.99（1.64-2.42）和2.06（1.74-2.43）。在对收缩压、体重指数、hsCRP、糖化血红蛋白、HDL-胆固醇、LDL-胆固醇和甘油三酯进行额外校正后，LPIR评分仍然与安慰剂组（1.35[1.03-1.76]）和瑞舒伐他汀组（1.60[1.27-2.03]）的糖尿病相关。12个月时也出现了类似的趋势。LPIR评分改善了模型似然比（卡方= 18.23，p<0.001）和分类净重新分类指数（0.039[0.003，0.072];非事件[0.036];事件[0.002]）。c-统计量和综合辨别力改善指数没有改善。在表面健康的人群中，LPIR评分（一种脂蛋白胰岛素抵抗的测量方法）与包括瑞舒伐他汀治疗期间在内的糖尿病事件呈正相关。
Statins decrease low-density lipoproteins, triglycerides, and cardiovascular events, but increase the risk of being diagnosed with diabetes. The risk factors associated with incident diabetes are incompletely characterized. To investigate the association of lipoprotein subclasses and size, and a novel lipoprotein insulin resistance (LPIR) score (a composite of six lipoprotein measures), with incident diabetes among individuals randomized to high-intensity statin or placebo. JUPITER was an international, randomized, double-blind, placebo-controlled trial. A prespecified secondary aim was to assess the effect of rosuvastatin on diabetes, and incident diabetes was monitored for a median of 2.0 years. The study was conducted at 1315 sites in 26 countries. JUPITER comprised 17802 men ≥50 years and women ≥60 years with LDL cholesterol <130 mg/dL, hsCRP ≥2 mg/L, and triglycerides <500mg/dL. Those with diabetes were excluded. Rosuvastatin, 20mg daily, or placebo. Among 11918 participants in JUPITER, we measured baseline size and concentration of lipids, apolipoproteins, and lipoproteins and, in 9180 of these, at 12 months after randomization to rosuvastatin or placebo. LPIR score, a correlate of insulin resistance, was calculated as a weighted combination of size and concentration of LDL, very low-density lipoprotein(VLDL), and high-density lipoprotein(HDL) particles. Rosuvastatin lowered LDL particles(−49%), VLDL particles(−20%), and triglycerides(−15%), and shifted the lipoprotein subclass distribution towards smaller LDL size(−2%), larger VLDL size(3%), and lower LPIR score(−3%). In analyses adjusted for age, sex, race/ethnic origin, exercise, education, family history, and smoking, the hazard ratio for diabetes per standard deviation of LPIR score was 1.99 (1.64–2.42) in placebo and 2.06 (1.74–2.43) in rosuvastatin-allocated individuals. After additional adjustment for systolic blood pressure, body-mass index, hsCRP, glycated hemoglobin, HDL-cholesterol, LDL-cholesterol, and triglycerides, LPIR score remained associated with diabetes in placebo- (1.35[1.03–1.76]) and rosuvastatin-allocated individuals (1.60[1.27–2.03]). Similar trends were seen at 12 months. LPIR score improved the model likelihood ratio (chi-squared = 18.23, p<0.001) and categorical net reclassification index (0.039[0.003, 0.072]; non-events[0.036]; events[0.002]). The c-statistic and integrated discrimination improvement index did not improve. In apparently healthy people, LPIR score, a measure of lipoprotein insulin resistance, was positively associated with incident diabetes including during rosuvastatin therapy.