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

BACKGROUND: Type 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 ß-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. METHODS: We 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. RESULTS: We 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. CONCLUSION: Subjects 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.

Fibroblast growth factor 21 is associated with increased serum total antioxidant capacity and oxidized lipoproteins in humans with different stages of chronic kidney disease.

Background and aims: Oxidative stress (OS) induces the production of fibroblast growth factor 21 (FGF21). Previous data have revealed that FGF21 protects cells from OS injury and death, making it a potential therapeutic option for many diseases with increased OS. However, the association of this growth factor with OS markers in humans with chronic kidney disease (CKD) remains unknown. This study aims to evaluate the association of serum FGF21 with serum total antioxidant capacity (TAC) and oxidized low-density lipoproteins (OxLDL) in subjects in different stages of kidney disease. Methods: This is a cross-sectional study that included 382 subjects with different stages of CKD, irrespective of type 2 diabetes (T2D) diagnosis. Associations of serum FGF21 with OxLDL, TAC, sex, age, body mass index (BMI), fasting plasma glucose, estimated glomerular filtration rate (eGFR), T2D, and smoking, were evaluated through bivariate and partial correlation analyses. Independent associations of these variables with serum FGF21 were evaluated using multiple linear regression analysis. Results: Serum FGF21 was significantly and positively correlated with age (r = 0.236), TAC (lnTAC) (r = 0.217), and negatively correlated with eGFR (r = -0.429) and male sex (r = -0.102). After controlling by age, sex, BMI, T2D, smoking, and eGFR; both TAC and OxLDL were positively correlated with FGF21 (r = 0.117 and 0.158 respectively, p < 0.05). Using multiple linear regression analysis, eGFR, male sex, T2D, OxLDL, and TAC were independently associated with serum FGF21 (STDß = -0.475, 0.162, -0.153, 0.142 and 0.136 respectively; p < 0.05 for all) adjusted for age, BMI, smoking, and fasting plasma glucose. Conclusion: A positive association between serum FGF21 and OS has been found independently of renal function in humans. Results from the present study provide novel information for deeper understanding of the role of FGF21 in OS in humans with CKD and T2D; mechanistic studies to explain the association of serum FGF21 with oxidative stress in CKD are needed.