Investigation of the mechanisms of therapy-related hypoglycaemia in children with acute lymphoblastic leukaemia
Investigation of the mechanisms of therapy-related hypoglycaemia in children with acute lymphoblastic leukaemia
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DOI：
10.1111/j.1651-2227.2003.tb00466.x
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发表时间：
2003-01-01
期刊：
影响因子：
3.8
通讯作者：
Mäkipernaa, A
中科院分区：
文献类型：
--
作者：
Halonen, P;Salo, MK;Mäkipernaa, A
目的：探讨儿童急性淋巴细胞白血病（ALL）维持治疗（MT）期间空腹低血糖发生的机制。方法：35名患有ALL的儿童和青少年，年龄在2.4-17.4岁，在MT期间禁食长达16小时。19名儿童在禁食11 - 16小时后出现低血糖。在禁食结束后采集血液样本以测定代谢变化。19例患者在MT期间禁食4 ~ 16小时后进行胰高血糖素刺激试验。空腹时测定甲氨蝶呤（E-MTX）和6-巯基嘌呤（E-TGN）代谢产物的红细胞浓度。19例低血糖患者中有15例在停止治疗3 - 4个月后重新研究。结果：低血糖组血浆糖异生氨基酸丙氨酸和谷氨酰胺水平低于正常血糖组（中位数分别为117和190 μ mol L-1， p = 0.009，中位数分别为396和448 μ mol L-1， p = 0.031）。血清游离肉碱水平较低（中位数为20.3 mmol - L-1 vs 29.8 mmol - L-1, p = 0.027），游离脂肪酸水平较高（中位数为3.09 mmol - L-1 vs 1.23 mmol - L-1, p < 0.001），显著的二羧酸尿在低血糖患者中更为常见（14/16组vs 2/14组，p < 0.001）。低血糖组对胰高血糖素刺激反应受损的比例为36%(4/11)，正常血糖组为12.5% (1/8)（p = 0.243）。各组间E-MTX和E-TGN无显著差异。大多数代谢异常在化疗停止后恢复正常。结论：低水平的糖异生氨基酸，尤其是丙氨酸，与低血糖有关。肝糖原储存减少也可能与病因有关。
Aim: To determine the mechanisms of fasting hypoglycaemia occurring during maintenance therapy (MT) for childhood acute lymphoblastic leukaemia (ALL). Methods: Thirty-five children and adolescents with ALL, aged 2.4-17.4 y, were fasted for up to 16 h during MT. Nineteen of the children developed hypoglycaemia after 11 to 16 h of fasting. Blood samples for determination of metabolic changes were taken on completion of fasting. Nineteen patients underwent a glucagon stimulation test after 4 to 16 h of fasting during MT. Erythrocyte concentrations of the metabolites of methotrexate (E-MTX) and 6-mercaptopurine (E-TGN) were measured at the time of fasting. Fifteen out of 19 patients who became hypoglycaemic were re-studied 3 to 4 mo after cessation of therapy. Results: In the hypoglycaemia group, plasma levels of gluconeogenic amino acids alanine and glutamine were lower (medians 117 vs 190 mumol L-1, p = 0.009, and medians 396 vs 448 mumol L-1, p = 0.031, respectively) than in the normoglycaemia group. Serum levels of free carnitine were lower (medians 20.3 vs 29.8 mumol L-1, p = 0.027), free fatty acids higher (medians 3.09 vs 1.23 mmol L-1, p < 0.001) and marked dicarboxylic aciduria was more common in the patients with hypoglycaemia (in 14/16 vs in 2/14, p < 0.001). Impaired responses to glucagon stimulation occurred in 36% (4/11) in the hypoglycaemia group and in 12.5% (1/8) in the normoglycaemia group (p = 0.243). No significant differences were detected in E-MTX and E-TGN between the groups. Most of the metabolic abnormalities returned to normal after cessation of chemotherapy.Conclusions: Low levels of gluconeogenic amino acids, especially of alanine, are associated with hypoglycaemia. Reduced hepatic glycogen stores may also be involved in the aetiology.