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Published in: BMC Endocrine Disorders 1/2018

Open Access 01-12-2018 | Research article

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

Authors: Miguel Ángel Gómez-Sámano, Jorge Enrique Baquerizo-Burgos, Melissa Fabiola Coronel Coronel, Buileng Daniela Wong-Campoverde, Fernando Villanueva-Martinez, Diego Molina-Botello, Jose Alonso Avila-Rojo, Lucía Palacios-Báez, Daniel Cuevas-Ramos, Francisco Javier Gomez-Perez, Alejandro Zentella-Dehesa, Álvaro Aguayo-González, Alfonso Gulias-Herrero

Published in: BMC Endocrine Disorders | Issue 1/2018

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Abstract

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 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.

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.
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Literature
2.
go back to reference Agostino NM, Chinchilli VM, Lynch CJ, Koszyk-Szewczyk A, Gingrich R, Sivik J, et al. Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice. J Oncol Pharm Pract. 2011;17:197–202. https://doi.org/10.1177/1078155210378913.CrossRefPubMed Agostino NM, Chinchilli VM, Lynch CJ, Koszyk-Szewczyk A, Gingrich R, Sivik J, et al. Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice. J Oncol Pharm Pract. 2011;17:197–202. https://​doi.​org/​10.​1177/​1078155210378913​.CrossRefPubMed
4.
go back to reference Mokhtari D, Welsh N. Potential utility of small tyrosine kinase inhibitors in the treatment of diabetes. Clin Sci (Lond). 2010;118:241–7.CrossRef Mokhtari D, Welsh N. Potential utility of small tyrosine kinase inhibitors in the treatment of diabetes. Clin Sci (Lond). 2010;118:241–7.CrossRef
5.
go back to reference Lau J, Zhou Q, Sutton SE, Herman AE, Schmedt C, Glynne R. Inhibition of c-kit is not required for reversal of hyperglycemia by imatinib in NOD mice. PLoS One. 2014;9:1–5. Lau J, Zhou Q, Sutton SE, Herman AE, Schmedt C, Glynne R. Inhibition of c-kit is not required for reversal of hyperglycemia by imatinib in NOD mice. PLoS One. 2014;9:1–5.
9.
go back to reference Dingli D, Wolf RC, Vella A. Imatinib and type 2 diabetes. Endocr Pract. 2007;13:126–30.CrossRef Dingli D, Wolf RC, Vella A. Imatinib and type 2 diabetes. Endocr Pract. 2007;13:126–30.CrossRef
10.
go back to reference Lee JP, Birnstein E, Masiello D, Yang D, Yang AS. Gender and ethnic differences in chronic myelogenous leukemia prognosis and treatment response: a single-institution retrospective study. J Hematol Oncol. 2009;2:30.CrossRef Lee JP, Birnstein E, Masiello D, Yang D, Yang AS. Gender and ethnic differences in chronic myelogenous leukemia prognosis and treatment response: a single-institution retrospective study. J Hematol Oncol. 2009;2:30.CrossRef
11.
go back to reference Akash MSH, Rehman K, Chen S. Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus. J Cell Biochem. 2013;114:525–31.CrossRef Akash MSH, Rehman K, Chen S. Role of inflammatory mechanisms in pathogenesis of type 2 diabetes mellitus. J Cell Biochem. 2013;114:525–31.CrossRef
12.
go back to reference Xia CQ, Zhang P, Li S, Yuan L, Xia T, Xie C, et al. C-Abl inhibitor imatinib enhances insulin production by β cells: C-Abl negatively regulates insulin production via interfering with the expression of NKx2.2 and GLUT-2. PLoS One. 2014;9:1–11. Xia CQ, Zhang P, Li S, Yuan L, Xia T, Xie C, et al. C-Abl inhibitor imatinib enhances insulin production by β cells: C-Abl negatively regulates insulin production via interfering with the expression of NKx2.2 and GLUT-2. PLoS One. 2014;9:1–11.
13.
go back to reference Wolf AM, Wolf D, Rumpold H, Ludwiczek S, Enrich B, Gastl G, et al. The kinase inhibitor imatinib mesylate inhibits TNF-α production in vitro and prevents TNF-dependent acute hepatic inflammation. Proc Natl Acad Sci U S A. 2005;102:13622–7.CrossRef Wolf AM, Wolf D, Rumpold H, Ludwiczek S, Enrich B, Gastl G, et al. The kinase inhibitor imatinib mesylate inhibits TNF-α production in vitro and prevents TNF-dependent acute hepatic inflammation. Proc Natl Acad Sci U S A. 2005;102:13622–7.CrossRef
16.
go back to reference Fitter S, Vandyke K, Schultz CG, White D, Hughes TP, Zannettino ACW. Plasma adiponectin levels are markedly elevated in imatinib-treated chronic myeloid leukemia (CML) patients: a mechanism for improved insulin sensitivity in type 2 diabetic CML patients? J Clin Endocrinol Metab. 2010;95:3763–7. https://doi.org/10.1210/jc.2010-0086.CrossRefPubMed Fitter S, Vandyke K, Schultz CG, White D, Hughes TP, Zannettino ACW. Plasma adiponectin levels are markedly elevated in imatinib-treated chronic myeloid leukemia (CML) patients: a mechanism for improved insulin sensitivity in type 2 diabetic CML patients? J Clin Endocrinol Metab. 2010;95:3763–7. https://​doi.​org/​10.​1210/​jc.​2010-0086.CrossRefPubMed
18.
go back to reference Mokhtari D, Al-Amin A, Turpaev K, Li T, Idevall-Hagren O, Li J, et al. Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells: role of Src homology 2-containing inositol 5′-phosphatase interaction with c-Abl. Diabetologia. 2013;56:1327–38.CrossRef Mokhtari D, Al-Amin A, Turpaev K, Li T, Idevall-Hagren O, Li J, et al. Imatinib mesilate-induced phosphatidylinositol 3-kinase signalling and improved survival in insulin-producing cells: role of Src homology 2-containing inositol 5′-phosphatase interaction with c-Abl. Diabetologia. 2013;56:1327–38.CrossRef
22.
go back to reference Salaroli A, Loglisci G, Serrao A, Alimena G, Breccia M. Fasting glucose level reduction induced by imatinib in chronic myeloproliferative disease with TEL-PDGFRβ rearrangement and type 1 diabetes. Ann Hematol. 2012;91:1823–4.CrossRef Salaroli A, Loglisci G, Serrao A, Alimena G, Breccia M. Fasting glucose level reduction induced by imatinib in chronic myeloproliferative disease with TEL-PDGFRβ rearrangement and type 1 diabetes. Ann Hematol. 2012;91:1823–4.CrossRef
23.
go back to reference Iurlo A, Orsi E, Cattaneo D, Resi V, Orofino N, Sciumè M, et al. Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients : a real clinical problem ? Oncotarget. 2015;6:33944–51.CrossRef Iurlo A, Orsi E, Cattaneo D, Resi V, Orofino N, Sciumè M, et al. Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients : a real clinical problem ? Oncotarget. 2015;6:33944–51.CrossRef
24.
go back to reference Breccia M, Muscaritoli M, Cannella L, Stefanizzi C, Frustaci A, Alimena G. Fasting glucose improvement under dasatinib treatment in an accelerated phase chronic myeloid leukemia patient unresponsive to imatinib and nilotinib. Leuk Res. 2008;32:1626–8.CrossRef Breccia M, Muscaritoli M, Cannella L, Stefanizzi C, Frustaci A, Alimena G. Fasting glucose improvement under dasatinib treatment in an accelerated phase chronic myeloid leukemia patient unresponsive to imatinib and nilotinib. Leuk Res. 2008;32:1626–8.CrossRef
Metadata
Title
Effect of imatinib on plasma glucose concentration in subjects with chronic myeloid leukemia and gastrointestinal stromal tumor
Authors
Miguel Ángel Gómez-Sámano
Jorge Enrique Baquerizo-Burgos
Melissa Fabiola Coronel Coronel
Buileng Daniela Wong-Campoverde
Fernando Villanueva-Martinez
Diego Molina-Botello
Jose Alonso Avila-Rojo
Lucía Palacios-Báez
Daniel Cuevas-Ramos
Francisco Javier Gomez-Perez
Alejandro Zentella-Dehesa
Álvaro Aguayo-González
Alfonso Gulias-Herrero
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2018
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-018-0303-x

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