Predictors of Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-Binding Protein-3 in Critical Illness.
Predictors of Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-Binding Protein-3 in Critical Illness.
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DOI：
10.1097/ccm.0000000000001314
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发表时间：
2015-12
影响因子：
8.8
通讯作者：
Christiani DC
中科院分区：
文献类型：
--
作者：
Ahasic AM;Tejera P;Wei Y;Su L;Mantzoros CS;Bajwa EK;Thompson BT;Christiani DC
描述急性危重病中胰岛素样生长因子（IGF）-1和IGF结合蛋白（IGFBP）-3的预测因子，假设与危重病相关的急性因素比慢性临床或遗传因素更能预测循环IGF-1和IGFBP-3。在一项大型前瞻性研究中嵌套的观察性研究，使用多变量线性回归对循环IGF-1和IGFBP-3与急性和慢性临床变量以及IGF途径基因中5种多态性的基因型进行建模。从两个大型学术医学中心的重症监护室（ICU）招募了543例具有急性呼吸窘迫综合征（ARDS）危险因素并可从危重病早期获得血浆的白人患者。没有。使用IMMULITE测定法测量血浆中的总IGF-1和IGFBP-3。我们检查了年龄、性别、体重指数（BMI）、肝硬化和糖尿病，以及APACHE III评分、急性肝功能障碍、肺炎和吸入、脓毒症/脓毒性休克、ARDS和皮质类固醇的接受情况。BMI、肝硬化和ARDS与IGF-1和IGFBP-3水平密切相关; APACHE III与IGF-1水平密切相关;年龄与IGFBP-3密切相关。分析了5种多态性（IGF 1：rs 1520220、rs35767、rs 2946834; IGFBP 1：rs 4619; IGFBP 3：rs 2854746）与血浆水平的相关性。当将基因型添加到模型中时，rs 2854746与血浆IGFBP-3显著相关。基因型解释了额外的2%的变异性，总体调整R方为0.18。尽管危重病的急性紊乱，急性和慢性健康因素显着影响IGF-1和IGFBP-3的循环水平在危重病的早期。在该ICU队列中，Rs 2854746也与IGFBP-3水平显著相关。总体而言，表型和基因型因素仅解释了IGF-1和IGFBP-3的适度变异。需要进一步的研究来了解如何将这些发现应用于患者护理。
To characterize predictors of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in acute critical illness with the hypothesis that acute factors associated with critical illness will more strongly predict circulating IGF-1 and IGFBP-3 than chronic clinical or genetic factors. Observational study nested within a large prospective study using multivariable linear regression to model circulating IGF-1 and IGFBP-3 with acute and chronic clinical variables, and genotype from five polymorphisms in IGF pathway genes. Five-hundred forty-three Caucasian patients with risk factors for acute respiratory distress syndrome (ARDS) and available plasma from early in critical illness, recruited from intensive care units (ICUs) of two large academic medical centers. None. Total IGF-1 and IGFBP-3 were measured in plasma using IMMULITE assays. We examined age, gender, body mass index (BMI), cirrhosis, and diabetes, as well as APACHE III score, acute hepatic dysfunction, pneumonia and aspiration, sepsis/septic shock, ARDS, and receipt of corticosteroids. BMI, cirrhosis, and ARDS were strongly associated with IGF-1 and IGFBP-3 levels; APACHE III was strongly associated with IGF-1 levels; and age was strongly associated with IGFBP-3‥ Five polymorphisms (IGF1: rs1520220, rs35767, rs2946834; IGFBP1: rs4619; IGFBP3: rs2854746) were analyzed for associations with plasma levels. When genotypes were added to models, rs2854746 was significantly associated with plasma IGFBP-3. Genotype explained an additional 2% of variability with an overall adjusted R-square of 0.18. Despite the acute derangements of critical illness, both acute and chronic health factors significantly influence circulating levels of IGF-1 and IGFBP-3 early in critical illness. Rs2854746 is also significantly associated with IGFBP-3 levels in this ICU cohort. Overall, phenotypic and genotypic factors explained only a modest amount of variability in IGF-1 and IGFBP-3. Further research is needed to understand how to apply these findings to patient care.