Effect of imatinib on plasma glucose concentration in subjects with chronic myeloid leukemia and gastrointestinal stromal tumor

Abstract

BackgroundType 2 diabetes mellitus has become one of the most important public health concerns worldwide. Due to its high prevalence and morbidity, there is an avid necessity to find new therapies that slow the progression and promote the regression of the disease. Imatinib mesylate is a tyrosine kinase inhibitor that binds to the Abelson tyrosine kinase and related proteins. It enhances β-cell survival in response to toxins and pro-inflammatory cytokine. The aim of this study is to evaluate the effect of imatinib on fasting plasma glucose in subjects with normal fasting glucose, subjects with impaired fasting glucose and in subjects with type 2 diabetes mellitus.MethodsWe identified 284 subjects diagnosed with chronic myeloid leukemia or gastrointestinal stromal tumors from the Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran database. 106/284 subjects were treated with imatinib. We compared the effect of imatinib on fasting plasma glucose after 1 and 6 months of treatment. We used ANOVA test of repeated samples to determine statistical significance in fasting plasma glucose before imatinib treatment and the follow-up. Statistical analysis was performed with Statistical Package for the Social Sciences v22.ResultsWe included a total of 106 subjects: 76 with fasting plasma glucose concentrations < 100 mg/dL (normal FG), 19 subjects with fasting plasma glucose concentrations ≥100 mg/dL (impaired fasting glucose), and 11 subjects with ≥126 mg/dL (type 2 diabetes mellitus). We found a significant increase in fasting plasma glucose concentration in the normal fasting glucose group (p = 0.048), and a significant decrease in fasting plasma glucose concentration in the type 2 diabetes mellitus group (p = 0.042). In the impaired fasting glucose group, we also found a tendency towards a decrease in fasting plasma glucose (p = 0.076). We identified 11 subjects with type 2 diabetes mellitus, of whom, 7 (64%) had a reduction in their fasting plasma glucose concentrations after 6 months. A significant glycosylated hemoglobin reduction (p = 0.04) was observed.ConclusionSubjects with chronic myeloid leukemia or gastrointestinal stromal tumor with type 2 diabetes mellitus had a significant reduction in fasting plasma glucose and glycosylated hemoglobin at 1 and 6 months while using imatinib.Electronic supplementary materialThe online version of this article (10.1186/s12902-018-0303-x) contains supplementary material, which is available to authorized users.

Tyrosine kinase signaling in and on the endoplasmic reticulum

“…How exactly ABL is activated by ER stress is not completely understood, but nevertheless, inhibition of ABL could be used therapeutically to prevent the loss of β-cells due to secretory exhaustion. In support of this, it was observed that patients that are treated with imatinib exhibited lower fasting glucose levels, indicative of an anti-diabetic effect of imatinib (39).…”

The Effect of BCR-ABL Specific Tyrosine Kinase Inhibitors on the Thioredoxin System in Chronic Myeloid Leukemia

“…TXNIP is involved in glucose metabolism and has been shown to be upregulated when glucose levels are high, in order to ensure glucose is metabolized correctly [61]. However, Gomez-Samano et al [62] has shown that imatinib reduces levels of plasma glucose, which in turn could explain why TXNIP is downregulated following imatinib treatment.…”

Apoptosis in Type 2 Diabetes, Can It be Prevented?

“…Multitarget tyrosine kinase inhibitors (TKIs), as the second group of small molecules (with a wide range of factors available), have been reported for years as potential candidates in the treatment of diabetes symptoms [114,115]. Clinical trials have shown a beneficial antidiabetic effect in patients with type 2 diabetes who had their symptoms relieved from imatinib, sunitinib, desatinib and elrotinib [116][117][118][119][120]. Although today the main goal is cancer therapy, and their action is based on ERBB2/EGFR inhibition, it has been noticed (in clinical observations) that they additionally alleviate the symptoms of diabetes [121,122].…”