酪氨酸激酶抑制剂（TKIs）治疗（尤其是尼洛替尼）常常导致高血糖，这可能进一步增加慢性髓细胞白血病（CML）患者心血管疾病的风险。 TKI诱导的葡萄糖失调的机制尚不清楚。建议TKIs会影响胰岛素分泌，但是外周组织的胰岛素敏感性也被提出在TKI诱导的高血糖的发病中发挥作用。因此，我们旨在评估非糖尿病CML患者接受TKI治疗时骨骼肌葡萄糖摄取和胰岛素反应是否改变。在一个缺乏糖原的锻炼会话之后，对14名接受尼洛替尼治疗的CML患者、14名接受伊马替尼治疗的CML患者和14个年龄和性别相匹配的非CML对照组患者进行静脉葡萄糖注射（0.3克/千克体重），以监测2小时的葡萄糖耐量和胰岛素反应。然后，在一个男性CML患者的子组中的动态[18F]-FDG PET扫描下进行高胰岛素-正常血糖稳定融合，以评估第四腰肌葡萄糖摄取。我们发现，接受尼洛替尼治疗的CML患者在肌肉糖原耗尽运动后，对静脉葡萄糖注射产生了增加的胰岛素反应。尽管接受尼洛替尼治疗的CML患者对葡萄糖注射产生了增加的胰岛素反应，但与控制组相比，在葡萄糖注射后的15分钟内，葡萄糖消失速率显著较慢。尽管[m.四头肌]的[18F]-FDG摄取没有差异，但接受尼洛替尼治疗的患者在正常血糖稳态下的葡萄糖输注速率有下降趋势，与接受伊马替尼治疗的患者相比。总之，这些发现表明接受尼洛替尼治疗的CML患者骨骼肌葡萄糖处理受到干扰。在这项研究中，我们发现接受尼洛替尼治疗的非糖尿病CML患者显示出早期的骨骼肌葡萄糖处理受到干扰的迹象，而在伊马替尼治疗患者中未观察到这种现象。这可能反映了尼洛替尼用户的肌肉胰岛素敏感性降低，可能成为对抗糖代谢失调的潜在靶点，此发现具有临床意义，因为这些患者患心血管疾病的风险增加。

Treatment with tyrosine kinase inhibitors (TKIs), especially nilotinib, often results in hyperglycemia, which may further increase cardiovascular disease risk in patients with chronic myeloid leukemia (CML). The mechanism underlying the TKI-induced glucose dysregulation is not clear. TKIs are suggested to affect insulin secretion but also insulin sensitivity of peripheral tissue has been proposed to play a role in the pathogenesis of TKI-induced hyperglycemia. Here, we aimed to assess whether skeletal muscle glucose uptake and insulin responses are altered in nondiabetic patients with CML receiving TKI treatment. After a glycogen-depleted exercise bout, an intravenous glucose bolus (0.3 g/kg body weight) was administered to monitor 2-h glucose tolerance and insulin response in 14 patients with CML receiving nilotinib, 14 patients with CML receiving imatinib, and 14 non-CML age- and gender-matched controls. A dynamic [18F]-FDG PET scan during a hyperinsulinemic-euglycemic clamp was performed in a subgroup of 12 male patients with CML to assess m. quadriceps glucose uptake. We showed that patients with CML treated with nilotinib have an increased insulin response to intravenous glucose administration after muscle glycogen-depleted exercise. Despite the increased insulin response to glucose administration in patients with CML receiving nilotinib, glucose disappearance rates were significantly slower in nilotinib-treated patients when compared with controls in the first 15 min after glucose administration. Although [18F]-FDG uptake in m. quadriceps was not different, patients receiving nilotinib showed a trend toward decreased glucose infusion rates during euglycemic clamping when compared with patients receiving imatinib. Together, these findings indicate disturbed skeletal muscle glucose handling in patients with CML receiving nilotinib therapy.NEW & NOTEWORTHY In this study, we have shown that non-diabetic patients with CML receiving nilotinib therapy show early signs of disturbed skeletal muscle glucose handling, which was not observed in imatinib-treated patients. These observations in nilotinib users may reflect decreased muscle insulin sensitivity, which could serve as a potential target to counteract glycemic dysregulation, and is of clinical importance since these patients have an increased cardiovascular disease risk.