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地塞米松治疗的小儿急性淋巴细胞白血病患者代谢综合征组分的急性激活

Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone.

作者信息

Warris Lidewij T, van den Akker Erica L T, Bierings Marc B, van den Bos Cor, Zwaan Christian M, Sassen Sebastiaan D T, Tissing Wim J E, Veening Margreet A, Pieters Rob, van den Heuvel-Eibrink Marry M

机构信息

Department of Pediatric Oncology, Erasmus MC- Sophia Children's Hospital, Rotterdam, The Netherlands.

Department of Pediatric Endocrinology, Erasmus MC- Sophia Children's Hospital, Rotterdam, The Netherlands.

出版信息

PLoS One. 2016 Jun 30;11(6):e0158225. doi: 10.1371/journal.pone.0158225. eCollection 2016.

Abstract

Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating pediatric ALL with dexamethasone administration with respect to activation of components of metabolic syndrome (MetS); in addition, we investigated whether these side effects were correlated with the level of dexamethasone. Fifty pediatric patients (3-16 years of age) with ALL were studied during a 5-day dexamethasone course during the maintenance phase of the Dutch Childhood Oncology Group ALL-10 and ALL-11 protocols. Fasting insulin, glucose, total cholesterol, HDL, LDL, and triglycerides levels were measured at baseline (before the start of dexamethasone; T1) and on the fifth day of treatment (T2). Dexamethasone trough levels were measured at T2. We found that dexamethasone treatment significantly increased the following fasting serum levels (P<0.05): HDL, LDL, total cholesterol, triglycerides, glucose, and insulin. In addition, dexamethasone increased insulin resistance (HOMA-IR>3.4) from 8% to 85% (P<0.01). Dexamethasone treatment also significantly increased the diastolic and systolic blood pressure. Lastly, dexamethasone trough levels (N = 24) were directly correlated with high glucose levels at T2, but not with other parameters. These results indicate that dexamethasone treatment acutely induces three components of the MetS. Together with the weight gain typically associated with dexamethasone treatment, these factors may contribute to the higher prevalence of MetS and cardiovascular risk among survivors of childhood leukemia who received dexamethasone treatment.

摘要

尽管地塞米松在治疗儿童急性淋巴细胞白血病(ALL)方面非常有效,但它会引起严重的代谢副作用。由于关于地塞米松作用的研究规模较小,存在局限性,我们前瞻性地研究了地塞米松治疗儿童ALL对代谢综合征(MetS)各组分激活的直接影响;此外,我们还研究了这些副作用是否与地塞米松水平相关。在荷兰儿童肿瘤学组ALL - 10和ALL - 11方案的维持阶段,对50例年龄在3至16岁的ALL患儿进行了为期5天地塞米松疗程的研究。在基线(地塞米松开始使用前;T1)和治疗第5天(T2)测量空腹胰岛素、血糖、总胆固醇、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和甘油三酯水平。在T2测量地塞米松谷浓度。我们发现地塞米松治疗显著提高了以下空腹血清水平(P<0.05):HDL、LDL、总胆固醇、甘油三酯、血糖和胰岛素。此外,地塞米松使胰岛素抵抗(HOMA - IR>3.4)从8%增加到85%(P<0.01)。地塞米松治疗还显著提高了舒张压和收缩压。最后,地塞米松谷浓度(N = 24)与T2时的高血糖水平直接相关,但与其他参数无关。这些结果表明,地塞米松治疗可急性诱发MetS的三个组分。连同通常与地塞米松治疗相关的体重增加,这些因素可能导致接受地塞米松治疗的儿童白血病幸存者中MetS和心血管风险的患病率更高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/467c/4928792/e1409a7b5e92/pone.0158225.g001.jpg

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