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Oncology Essentials

Controlling Malglycemia in Patients Undergoing Treatment for Cancer

Susan Storey
Veronica J. Brady
Ashley Leak Bryant
Ellen D. Davis
Marilyn J. Hammer
Denise Soltow Hershey
Jill Olausson
Jane Jeffrie Seley
CJON 2016, 20(1), 92-94 DOI: 10.1188/16.CJON.92-94

Patients with or without preexisting diabetes undergoing treatment for cancer may be at risk for malglycemic events. Malglycemia, particularly hyperglycemia and diabetes in patients with cancer, may lead to adverse outcomes. Prevention, prompt recognition, and early intervention to regulate malglycemia can optimize the effects of cancer treatment, minimize the harmful consequences, and improve quality of life for patients with cancer. The development of evidence-based standards of care and protocols are needed to guide clinical practice when caring for patients with cancer.

At a Glance

  • Malglycemia has been associated with increased risk for adverse patient outcomes.
  • Multiple known and unknown factors contribute to the onset of malglycemia.
  • Formal guidelines or protocols are needed to best manage malglycemia in patients receiving cancer treatment.

Context should be carefully considered when planning disease management and treatment (Bayliss et al., 2014). Typically, members of the healthcare team are focused on isolated disease management strategies, often failing to consider other pathophysiologic processes that can diminish the effectiveness of those very treatments. Educating members of the healthcare team regarding the deleterious effects of malglycemia (hyperglycemia, hypoglycemia, and/or glycemic variability) (Hammer et al., 2009) is imperative for the comprehensive care of patients with cancer. Understanding the pathophysiology and subsequent ramifications of malglycemia can result in preemptive assessment, early identification, intervention, and opportunities to educate the patient. The development of evidence-based standards of care and protocols for the treatment of malglycemia are needed to guide clinical practice when caring for patients with cancer. These best practices can be integrated into patients’ individualized treatment plans, thereby mitigating the untoward effects of malglycemia.

Background

Patients with established diabetes (American Diabetes Association, 2015) are at increased risk for developing certain types of cancers, such as liver, pancreatic, endometrial, colorectal, breast, and bladder cancers (Giovannucci et al., 2010) (see Figure 1). In addition, patients with or without preexisting diabetes undergoing treatment for cancer may be at risk for malglycemic events because of numerous factors, including steroids (Mazali, Lalli, Alves-Filho, & Mazzali, 2008) and certain chemotherapeutic agents (e.g., docetaxel [Taxotere®], everolimus [Afinitor®], temsirolimus [Torisel®], androgen deprivation therapy) (Hershey et al., 2014). In addition, higher body mass index (Roumen, Blaak, & Corpeleijn, 2009), nutritional imbalances (Butler, Btaiche, & Alaniz, 2005), nutritional support, stress (Butler et al., 2005), physical inactivity (Katz, 2007), and older age (Campisi & d’Adda di Fagagna, 2007) are potential contributors. Studies in patients who underwent treatment for hematologic malignancies (Storey & Von Ah, 2012) and, in particular, those who received allogeneic or autologous hematopoietic cell transplantations (Derr, Hsiao, & Saudek, 2008; Fuji et al., 2007; Hammer et al., 2009; Olausson, Hammer, & Brady, 2014) have shown associations between malglycemia and increased risks for adverse events, such as infection, toxicity, morbidity, and mortality.

Unknown Contributors

Although these patient and clinical factors are likely contributors to malglycemia, how to integrate these factors into comprehensive management guidelines is not fully understood. Underlying genetic and epigenetic factors likely contribute to an individual’s risk as well. In addition, the biophysiologic mechanisms between malglycemia and adverse events in patients undergoing treatment for cancer are not thoroughly understood, but they seem to involve immune function that is altered through an inflammatory response to hyperglycemic-induced oxidative stress (Yu, Jhun, & Yoon, 2011). In addition, the optimal therapeutic range for blood glucose is unknown, as are the best protocols for controlling glucose in patients with cancer.

Current Guidelines

No formal established guidelines or protocols are available regarding how to best manage malglycemia in patients undergoing cancer treatment. Oyer, Shah, and Bettenhausen (2006) offered an overview of approaches to the management of steroid-induced diabetes in patients with cancer, which ranged from the use of oral agents to insulin. Metformin (Glucophage®, Glumetza®, Glucophage XR®) has gained popularity for use in patients with cancer and diabetes, in part because of its reported protective effect (Simon & Balkau, 2010). An article by Brady, Grimes, Armstrong, and LoBiondo-Wood (2014) noted that the glycemic management of inpatients receiving steroids consisted primarily of insulin therapy. Jacob and Chowdhury (2015) suggested a variety of approaches to the management of diabetes, ranging from correction doses of insulin (if patient is not eating) to multiple-dose insulin therapy. Basal-bolus insulin therapy has been recommended for use in patients receiving high-dose steroids (Brady, Thosani, et al., 2014; Gosmanov, Goorha, Stelts, Peng, & Umpierrez, 2013). Although many are aware that hyperglycemia and diabetes in patients with cancer may lead to adverse outcomes, a lack of consensus exists, and wide variations in treatment algorithms are reportedly being used, indicating the need for the development of evidence-based standards of care.

Implications for Nursing and Conclusion

Prevention and early intervention is important because malglycemia, particularly hyperglycemia, has been shown to affect diagnostic imaging studies (Rabkin, Israel, & Keidar, 2010), alter response to treatment (Biernacka et al., 2013; Zeng et al., 2010), and influence progression of cancer (Duan et al., 2014; Ryu, Park, & Scherer, 2014). In addition, reviews of studies examining the impact of malglycemia have noted less than desirable health outcomes for patients who experience malglycemia (Olausson et al., 2014; Storey & Von Ah, 2015).

Malglycemia can be monitored using blood glucose meters or continuous glucose monitors, both of which require patient engagement to understand trends and patterns. Prevention, prompt recognition, and early intervention to regulate malglycemia can optimize the effects of cancer treatment, minimize the harmful consequences, and improve quality of life for patients with cancer.

References

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Bayliss, E.A., Bonds, D.E., Boyd, C.M., Davis, M.M., Finke, B., Fox, M.H., . . . Stange, K.C. (2014). Understanding the context of health for persons with multiple chronic conditions: Moving from what is the matter to what matters. Annals of Family Medicine, 12, 260–269. doi:10.1370/afm.1643

Biernacka, K.M., Uzoh, C.C., Zeng, L., Persad, R.A., Bahl, A., Gillatt, D., . . . Holly, J.M. (2013). Hyperglycaemia-induced chemoresistance of prostate cells due to IGFBP2. Endocrine-Related Cancer, 20, 741–751. doi:10.1530/ERC-13-0077

Brady, V.J., Grimes, D., Armstrong, T., & LoBiondo-Wood, G. (2014). Management of steroid-induced hyperglycemia in hospitalized patients with cancer: A review. Oncology Nursing Forum, 41, E355–E365. doi:10.1188/14.ONF.E355-E365

Brady, V., Thosani, S., Zhou, S., Bassett, R., Busaidy, N.L., & Lavis, V. (2014). Safe and effective dosing of basal-bolus insulin in patients receiving high-dose steroids for hyper-cyclophosphamide, doxorubicin, vincristine, and dexamethasone chemotherapy. Diabetes Technology and Therapeutics, 16, 874–879. doi:10.1089/dia.2014.0115

Butler, S.O., Btaiche, I.F., & Alaniz, C. (2005). Relationship between hyperglycemia and infection in critically ill patients. Pharmacotherapy, 25, 963–976. doi:10.1592/phco.2005.25.7.963

Campisi, J., & d’Adda di Fagagna, F. (2007). Cellular senescence: When bad things happen to good cells. Nature Reviews. Molecular Cell Biology, 8, 729–740. doi:10.1038/nrm2233

Derr, R.L., Hsiao, V.C., & Saudek, C.D. (2008). Antecedent hyperglycemia is associated with an increased risk of neutropenic infections during bone marrow transplantation. Diabetes Care, 31, 1972–1977. doi:10.2337/dc08-0574

Duan, W., Shen, X., Lei, J., Xu, Q., Yu, Y., Li, R., . . . Ma, Q. (2014). Hyperglycemia, a neglected factor during cancer progression. BioMed Research International, 2014, 461917. doi:10.1155/2014/461917

Fuji, S., Kim, S.W., Mori, S., Fukuda, T., Kamiya, S., Yamasaki, S., . . . Takaue, Y. (2007). Hyperglycemia during the neutropenic period is associated with a poor outcome in patients undergoing myeloablative allogeneic hematopoietic stem cell transplantation. Transplantation, 84, 814–820. doi:10.1097/01.tp.0000296482.50994.1c

Giovannucci, E., Harlan, D.M., Archer, M.C., Bergenstal, R.M., Gapstur, S.M., Habel, L.A., . . . Yee, D. (2010). Diabetes and cancer: A consensus report. Diabetes Care, 33, 1674–1685. doi:10.2337/dc10-0666

Gosmanov, A.R., Goorha, S., Stelts, S., Peng, L., & Umpierrez, G.E. (2013). Management of hyperglycemia in diabetic patients with hematologic malignancies during dexamethasone therapy. Endocrine Practice, 19, 231–235. doi:10.4158/EP12256.OR

Hammer, M.J., Casper, C., Gooley, T.A., O’Donnell, P.V., Boeckh, M., & Hirsch, I.B. (2009). The contribution of malglycemia to mortality among allogeneic hematopoietic cell transplant recipients. Biology of Blood and Marrow Transplantation, 15, 344–351. doi:10.1016/j.bbmt.2008.12.488

Hershey, D.S., Bryant, A.L., Olausson, J., Davis, E.D., Brady, V.J., & Hammer, M. (2014). Hyperglycemic-inducing neoadjuvant agents used in treatment of solid tumors: A review of the literature. Oncology Nursing Forum, 41, E343–E354. doi:10.1188/14.ONF.E343-E354

Jacob, P., & Chowdhury, T.A. (2015). Management of diabetes in patients with cancer. QJM, 108, 443–448. doi:10.1093/qjmed/hcu218

Katz, A. (2007). Modulation of glucose transport in skeletal muscle by reactive oxygen species. Journal of Applied Physiology, 102, 1671–1676. doi:10.1152/japplphysiol.01066.2006

Mazali, F.C., Lalli, C.A., Alves-Filho, G., & Mazzali, M. (2008). Posttransplant diabetes mellitus: Incidence and risk factors. Transplantation Proceedings, 40, 764–766. doi:10.1016/j.transproceed.2008.03.018

Olausson, J.M., Hammer, M.J., & Brady, V. (2014). The impact of hyperglycemia on hematopoietic cell transplantation outcomes: An integrative review. Oncology Nursing Forum, 41, E302–E312. doi:10.1188/14.ONF.E302-E312

Oyer, D.S., Shah, A., & Bettenhausen, S. (2006). How to manage steroid diabetes in the patient with cancer. Journal of Supportive Oncology, 4, 479–483.

Rabkin, Z., Israel, O., & Keidar, Z. (2010). Do hyperglycemia and diabetes affect the incidence of false-negative 18F-FDG PET/CT studies in patients evaluated for infection or inflammation and cancer? A comparative analysis. Journal of Nuclear Medicine, 51, 1015–1020. doi:10.2967/jnumed.109.074294

Roumen, C., Blaak, E.E., & Corpeleijn, E. (2009). Lifestyle intervention for prevention of diabetes: Determinants of success for future implementation. Nutrition Reviews, 67, 132–146. doi:10.1111/j.1753-4887.2009.00181.x

Ryu, T.Y., Park, J., & Scherer, P.E. (2014). Hyperglycemia as a risk factor for cancer progression. Diabetes and Metabolism Journal, 38, 330–336. doi:10.4093/dmj.2014.38.5.330

Simon, D., & Balkau, B. (2010). Diabetes mellitus, hyperglycaemia and cancer. Diabetes and Metabolism, 36, 182–191. doi:10.1016/j.diabet.2010.04.001

Storey, S., & Von Ah, D. (2012). Impact of malglycemia on clinical outcomes in hospitalized patients with cancer: A review of the literature. Oncology Nursing Forum, 39, 458–465. doi:10.1188/12.ONF.458-465

Storey, S., & Von Ah, D. (2015). Prevalence and impact of hyperglycemia on hospitalized leukemia patients. European Journal of Oncology Nursing, 19, 13–17. doi:10.1016/j.ejon.2014.08.005

Yu, T., Jhun, B.S., & Yoon, Y. (2011). High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission. Antioxidants and Redox Signaling, 14, 425–437. doi:10.1089/ars.2010.3284

Zeng, L., Biernacka, K.M., Holly, J.M., Jarrett, C., Morrison, A.A., Morgan, A., . . . Perks, C.M. (2010). Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: The role of fatty acid synthase. Endocrine-Related Cancer, 17, 539–551. doi:10.1677/ERC-09-0221

About the Author(s)

Susan Storey, PhD, RN, AOCNS®, is a research scientist in the School of Nursing at Indiana University in Indianapolis; Veronica J. Brady, PhD, FNP-BC, BCADM, CDE, is a nurse practitioner in the Department of Internal Medicine at the University of Nevada in Reno; Ashley Leak Bryant, PhD, RN-BC, OCN®, is an assistant professor in the College of Nursing at the University of North Carolina–Chapel Hill; Ellen D. Davis, MS, RN, CDE, FAADE, is a diabetes clinical nurse specialist at the Duke University Health System in Durham, NC; Marilyn J. Hammer, PhD, DC, RN, is an assistant professor in the College of Nursing at New York University in New York; Denise Soltow Hershey, PhD, FNPBC, is an assistant professor in the College of Nursing at Michigan State University in East Lansing; Jill Olausson, MSN, BSN, CDE, is an assistant professor in the School of Nursing at Azusa Pacific University in California; and Jane Jeffrie Seley, DNP, MSN, MPH, GNP, BC-ADM, CDE, CDTC, FAAN, is a diabetes nurse practitioner in the Weill Cornell Medical Center at New York–Presbyterian Hospital in New York, NY. The authors take full responsibility for the content of the article. The authors did not receive honoraria for this work. No financial relationships relevant to the content of this article have been disclosed by the authors or editorial staff. Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Clinical Journal of Oncology Nursing or the Oncology Nursing Society. Storey can be reached at sustorey@iu.edu, with copy to editor at CJONEditor@ons.org.

 

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