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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 45  |  Issue : 3  |  Page : 129-135

Glucocorticoid-induced hyperglycemia in oncohematological patients


1 Department of Internal Medicine, Al-Azhar University, Faculty of Medicine, Cairo; College of Medicine, Shaqra University, Shaqra, Kingdom of Saudi Arabia KSA, Egypt
2 Department of Internal Medicine, Al-Azhar University, Faculty of Medicine, Cairo, Egypt
3 Departement of Oncology, Al-Azhar University, Faculty of Medicine, Cairo, Egypt
4 Clinical Pathology, Al Azhar University, Faculty of Medicine, Cairo, Egypt

Date of Submission29-Dec-2019
Date of Acceptance22-Jan-2020
Date of Web Publication23-Jun-2021

Correspondence Address:
Hosameldeen S Shabana
Department of Internal Medicine, Al-Azhar University, Faculty of Medicine, Cairo, Egypt. College of Medicine, Shaqra University, Shaqra
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejh.ejh_63_19

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  Abstract 


Background Glucocorticoids are a common component of systemic chemotherapy regimens for hematological malignancy. Steroid-induced hyperglycemia remains a common potentially harmful problem that must be considered when using any type of glucocorticoids. Little is known about the impact of hyperglycemia associated with steroid use on treatment morbidity, infectious complications, as well as disease remission and mortality.
Objective The aim of the current work is to study glucocorticoid-induced hyperglycemia in patients with hematologic malignancies receiving repeated short-term pulse cycles of glucocorticoids (5–7 days), to estimate its prevalence, to define the risk factors, and to assess treatment response.
Patients and methods The prospective study included 30 adult patients with acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, and chronic lymphocytic leukemia attending the outpatient clinic of Al Hussein Hospital, Al Azhar University during the period between November 2015 and April 2016. During the period of the study, 30 patients received a total of 60 cycles of chemotherapy including corticosteroid.
Results Out of the 30 study patients, 15 (50%) were men and 15 (50%) were women with a mean age of 44.17. Corticosteroid-induced hyperglycemia was documented in 12 patients after one or more than one cycle (12/30–40%). Among the 60 cycles, corticosteroid-induced hyperglycemia was documented after 19 cycles (19/60–31%). The age of the patient was found to be the most important factor that affected the occurrence of hyperglycemia after corticosteroid where younger patients were less likely to develop hyperglycemia (P=0.013). Patients with BMI less than or equal to 25 had the lowest chance to develop hyperglycemia after corticosteroid. However, this difference was not statistically significant. The three patients who developed persistent hyperglycemia received hypoglycemic medications.
Conclusion About one-third of patients with hematological malignancies receiving glucocorticoids may develop hyperglycemia. To allow for early detection and effective treatment, these patients should be screened for hyperglycemia at least before each cycle and 4–6 h after glucocorticoids intake, especially old obese patients Appropriate guidelines for the diagnosis and treatment of steroid-induced diabetes are needed in order to prevent complications associated with the hyperglycemic state

Keywords: glucocorticoid, induced hyperglycemia, oncohematological patients


How to cite this article:
Shabana HS, Bazeed M, Nayel H, Attia M, Elwan M. Glucocorticoid-induced hyperglycemia in oncohematological patients. Egypt J Haematol 2020;45:129-35

How to cite this URL:
Shabana HS, Bazeed M, Nayel H, Attia M, Elwan M. Glucocorticoid-induced hyperglycemia in oncohematological patients. Egypt J Haematol [serial online] 2020 [cited 2021 Sep 23];45:129-35. Available from: http://www.ehj.eg.net/text.asp?2020/45/3/129/319162




  Introduction Top


The prevalence of hyperglycemia in the course of steroid administration ranges according to various authors from 16 to 35% in patients with hematological diseases [1]. Mechanisms for glucocorticoid-induced hyperglycemia include alteration of insulin sensitivity in the peripheral tissue and promotion of proteolysis, lipolysis, and hyperglycemia by increasing hepatic gluconeogenesis [2]. The subgroup of higher risk for glucocorticoid-induced hyperglycemia consisted of patients who fulfilled at least one of the following criteria: old age, family history of diabetes mellitus (DM), or obesity in first-degree or second-degree relatives and BMI more than the 95th percentile [3],[4]. The negative influence of hyperglycemia on the human immune system is well acknowledged. Patients with hematologic malignancies who develop hyperglycemia during chemotherapy may face an increased risk of developing complicated life-threatening infections as well as increased overall mortality and disease recurrence [4]. The improvement of glucocorticoid-induced hyperglycemia detection may constitute the first step toward the reduction of unfavorable consequences of hyperglycemia in these subsets of patients. However, the diagnosis based on clinical symptoms is difficult. The majority of hyperglycemic status in oncohematological patients treated with glucocorticoid may remain undiagnosed. Only an active search for hyperglycemia in patients receiving glucocorticoid therapy enables early diagnosis and introduction of appropriate treatment allowing for reduction of hyperglycemia negative effects [1],[2],[4].

Glucocorticoid-induced hyperglycemia in leukemia patients under induction therapy receiving a prolonged course of high-dose glucocorticoids has been widely studied [3],[5]. However, few studies assessed hyperglycemia that may be induced by repeated short-term pulse cycles of glucocorticoid therapy (5–7 days), whereas Lee et al. [4] found that 32.5% of patients receiving cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (CHOP) developed glucocorticoid-induced diabetes.

The aim of the present work is to study glucocorticoid-induced hyperglycemia in patients with hematologic malignancies receiving repeated short-term pulse cycles of glucocorticoids (5–7 days), in an attempt to estimate the prevalence, define the risk factors, and to assess the treatment response of glucocorticoid-induced persistent hyperglycemia.


  Patients and methods Top


The current prospective study included 30 patients with hematologic malignancies (60 cycles) attending the Hematology Unit, Oncology Department, Faculty of Medicine, Al Hussein Hospital, Al Azhar University during the period between September 2015 and May 2016. The study protocol was approved by the Ethics Committee of the faculty of medicine Al-Azhar University. All participants signed informed consent for using their data in the study. Patients included in the current study were cases of high-grade non-Hodgkin’s lymphoma under CHOP combination chemotherapy, chronic lymphocytic leukemia or low-grade lymphoma under cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy, or acute lymphoblastic leukemia (ALL) under St Jude total XV protocol in remission on maintenance therapy (beyond week 21) ([Table 1]).
Table 1 Chemotherapy regimens

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All patients were asked about a family history of diabetes. The data about the diagnosis and the disease statuses as well as the history of previously received corticosteroids (date, dose, and duration) were collected from the medical files. Glycated hemoglobin level was asked for all patients before to be included in the study group. Patients with a known history of DM or glycated hemoglobin levels more than or equal to 6.5% were excluded from the study group.

The BMI was measured for the whole study group just before each cycle. In this study, the BMI more than 30 kg/m2 is used to diagnose central obesity instead of waist measurement. BMI is to be calculated according to the recommendation of the International Diabetes Federation (REF) as follows: an individual’s body mass (kg)/square of their height (m2). For the purpose of this study, glucocorticoid-induced hyperglycemia was defined as a plasma glucose concentration of more than or equal to 200 mg/dl in two or more determinations related to (during or just after) the cycle of chemotherapy. This definition is consistent with the guidelines of the American Diabetes Association [6].

The day before receiving the cycle of chemotherapy (day 0), fasting and random blood sugar and glycated hemoglobin were measured. Thereafter, the fasting and random blood sugar were repeated on the last day of therapy day 5 and day 8. If the patient is diagnosed to have glucocorticoid-induced hyperglycemia, the measurement was repeated every other day until the disappearance of transient hyperglycemia. If hyperglycemia persists for more than 3 weeks, the patient was considered to have persistent hyperglycemia and to receive antidiabetic drugs with close monitoring during the subsequent cycles.


  Results Top


The current study included 30 adult patients with ALL, non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia attending the outpatient clinic of Al Hussein Hospital, Al Azhar University during the period between November 2015 and April 2016. During the period of study, 30 patients received a total of 60 cycles of chemotherapy including corticosteroid.

Corticosteroid-induced hyperglycemia was documented in 12 patients after one or more cycles (12/30–40%). Among the 60 cycles, corticosteroid-induced hyperglycemia was documented after 19 cycles (19/60–31%) ([Figure 1],[Figure 2],[Figure 3],[Figure 4]).
Figure 1 Corticosteroid-induced hyperglycemia among patients with lympho-reticular neoplasm under chemotherapy (60 cycles).

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Figure 2 Corticosteroid-induced persistent hyperglycemia among patients with lympho-reticular neoplasm under chemotherapy (30 patients).

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Figure 3 Corticosteroid induced persistent hyperglycemia among patients with lympho-reticular neoplasm under chemotherapy (60 cycles).

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Figure 4 Corticosteroid-induced persistent/transient hyperglycemia among patients with lympho-reticular neoplasm under chemotherapy (19 cycles).

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To identify the impact and relative importance of the clinical risk factors for glucocorticoid-induced hyperglycemia, the risk factors for patients who developed corticosteroid-induced hyperglycemia ([Table 2]) as well as in a total of 60 cycles ([Table 3]) were compared with those of the other group, who did not develop corticosteroid-induced hyperglycemia. The age of the patient was found to be the most important factor that affected the occurrence of hyperglycemia after corticosteroid where younger patients were less likely to develop hyperglycemia (P=0.013). Patients with BMI less tha
Table 2 Clinical risk factors of patients who developed corticosteroid-induced hyperglycemia after one or more cycles compared with those who did not develop corticosteroid-induced hyperglycemia

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Table 3 Clinical risk factors of patients who developed corticosteroid-induced hyperglycemia in a total of 60 cycles compared with those of the other group who did not develop corticosteroid-induced hyperglycemia

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n or equal to 25 had the lowest chance to develop hyperglycemia after corticosteroid. However, this difference was not statistically significant (P=0.24)

In the current study, the course of corticosteroid-induced hyperglycemia that was documented in 12 out of the 30 patients was followed up. All the episodes of corticosteroid-induced hyperglycemia were transient not necessitating treatment except in three patients (3/12–25%). The three patients who developed persistent hyperglycemia received hypoglycemic medications to control blood glucose levels during the subsequent cycles. Two patients received subcutaneous insulin while the third patient refused insulin and was treated by oral hypoglycemic drug (metformin). The blood glucose level was well controlled on medications for the three patients during the subsequent cycles.


  Discussion Top


Glucocorticoids is the basis of almost all chemotherapy regimens used for hematologic malignancies, As is well known, abnormal glucose metabolism resulting in medication-induced DM is one of the major adverse effects in patients who receive glucocorticoid therapy [7]. Hyperglycemia can occasionally cause acute complications such as hyperosmolar hyperglycemia syndrome, diabetic ketoacidosis, or increased risk of infections. Moreover, hyperglycemia has been associated with reduced overall and disease-free survival in patients with some solid tumors and leukemia [4],[8].

In fact, comparing the results of different studies may not give a firm conclusion about the prevalence of corticosteroid-induced hyperglycemia, as it has been defined in diverse ways in the literature. Belgaumi et al. [9] documented hyperglycemia when the patient required dietary change or insulin use. However, Pui et al. [10] and Baillargeon et al. [11] defined hyperglycemia as at least two random plasma glucose values greater than 200 mg/dl or fasting levels greater than 140 mg/dl. In our study, the definition of hyperglycemia was similar to that reported by Pui et al. [10] and Baillargeon et al. [11].

As regards hematologic malignancies, the prevalence of glucocorticoid-induced hyperglycemia was 37% in patients with ALL [8] and ranged from 32.5 [4] to 43.2% [12] for patients with NHL. In our study, we reported results comparable to that reported in the literature for corticosteroid-induced hyperglycemia in hematologic malignancies. Corticosteroid-induced hyperglycemia was documented in 12 patients after one or more than one cycle (12/30–40%) and after 19 cycles (19/60–31%).

There is great controversy about the relative impact of the known possible risk factors on the development of glucocorticoid-induced hyperglycemia/DM. Family history of DM, previous steroid intake, type of corticosteroid, concurrent use of steroid and tacrolimus in patients with kidney transplantation, race and obesity represented with a BMI more than 30 kg/m2 at the initiation of treatment are considered as possible risk factor for gestional diabetes mellitus (GDM) development [13],[14].

In the current study, age of the patient was found to be the most important factor that affected the occurrence of hyperglycemia after corticosteroid, where younger patients were less likely to develop hyperglycemia (P=0.013). Patients with BMI less than or equal to 25 had the lowest chance to develop hyperglycemia after corticosteroid. However, this difference was not statistically significant (P=0.24). Family history of DM, previous use of steroids, and type of steroids was not a significantly associated risk factor.

Our study confirmed that the only risk factors that may have a positive impact on glucocorticoid-induced hyperglycemia/DM were obesity and age. Our results are comparable to those reported by Baillargeon et al. [11], Uzu et al. [15], and Lee et al. [4], who suggested that obesity and old age are consistently important risk factors for GDM development. However, Ha et al. [14] reported that age and a positive family history of DM, but not sex, were independent risk factors for DM.

During the period of our study, the course of corticosteroid-induced hyperglycemia was documented in 12 out of the 30 patients. All the episodes of corticosteroid-induced hyperglycemia were transient except in three patients (3/12–25%). Lee et al. [4] found that among the 80 patients with hematologic malignancies receiving glucocorticoids, 26 (32.5%) developed GDM and only four (4/26–15%) had persistent hyperglycemia. The incidence of persistent hyperglycemia among our patients seems higher than the study of Lee et al. [4]. However, this may be partly explained by the different definitions of glucocorticoid-induced hyperglycemia/diabetes in different studies. The three patients who developed persistent hyperglycemia in our study received hypoglycemic medications to control blood glucose levels during the subsequent cycles. Two patients received subcutaneous insulin while the third patient refused insulin and was treated by oral hypoglycemic drug (metformin). The blood glucose level was well controlled on medications for the three patients.

The current work was conducted to study glucocorticoid-induced hyperglycemia in patients with hematologic malignancies receiving repeated short-term pulse cycles of glucocorticoids (5–7 days) at our center in an attempt to assess the prevalence and to define the risk factors. Such data are mandatory as a first step for designing our protocol for early diagnosis and proper management of glucocorticoid-induced hyperglycemia among our patients with hematologic malignancies. Early diagnosis and management of such morbidity may alleviate its negative impact on prognosis and treatment results.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Irga N, Mysliwiec M, Osak M et al. Transient hyperglycemia − an underestimated problem of pediatric oncohaematology. Arch Med Sci 2012; 8:672–677.  Back to cited text no. 1
    
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Ferris HA, Kahn CR. New mechanisms of glucocorticoid-induced insulin resistance: make no bones about it. J Clin Invest 2012; 122:3854–3857.  Back to cited text no. 2
    
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Lowas S. Prevalence of transient hyperglycemia during induction chemotherapy for pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer 2009; 52:814–818.  Back to cited text no. 3
    
4.
Lee S, Kurita N, Yokoyama Y et al. Glucocorticoid-induced diabetes mellitus in patients with lymphoma treated with CHOP chemotherapy. Support Care Cancer 2014; 22:1385–1390.  Back to cited text no. 4
    
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Harris D et al. Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study. Curr Oncol 2013; 20:532–538.  Back to cited text no. 5
    
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American Diabetes Association. Type 2 diabetes in children and adolescents. Pediatrics 2000; 105:671–680.  Back to cited text no. 6
    
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Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer 2009; 16:1103–1123.  Back to cited text no. 7
    
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Weiser MA et al. Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with hypofractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer 2004; 100:1179–1185.  Back to cited text no. 8
    
9.
Belgaumi AF, Al-Bakrah M, Al-Mahr M et al. Dexamethasone associated toxicity during induction chemotherapy for childhood acute lymphoblastic leukemia is augmented by concurrent use of daunomycin. Cancer 2003; 97:2898–2903.  Back to cited text no. 9
    
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Pui C, Burghen G, Bowman W et al. Risk factors for hyperglycemia in children with leukemia receiving L-asparaginase and prednisone. J Pediatr 1981; 99:46–50.  Back to cited text no. 10
    
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Baillargeon J, Langevin AM, Mullins J et al. Transient hyperglycemia in Hispanic children with acute lymphoblastic leukemia. Pediatr Blood Cancer 2005; 45:960–963.  Back to cited text no. 11
    
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Brunello A, Kapoor R, Extermann M. Hyperglycemia during chemotherapy for hematologic and solid tumors is correlated with increased toxicity. Am J Clin Oncol 2011; 34:292–296.  Back to cited text no. 12
    
13.
Khanh VU, Busaidy N, Maria E et al. A randomized controlled trial of an intensive insulin regimen in hyperglycemic acute lymphoblastic leukemia patients. Clin Lymphoma Myeloma Leuk 2012; 12:355–362.  Back to cited text no. 13
    
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Ha Y, Lee KH, Jung S, Lee SW, Lee SK, Park YB. Glucocorticoid-induced diabetes mellitus in patients with systemic lupus erythematous treated with high-dose glucocorticoid therapy. Lupus 2011; 20:1027–1034.  Back to cited text no. 14
    
15.
Uzu T, Harada T, Sakaguchi M, Kanasaki M, Isshiki K, Araki S et al. Glucocorticoid-induced diabetes mellitus: prevalence and risk factors in primary renal diseases. Nephron Clin Pract 2007; 105:54–57.  Back to cited text no. 15
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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