Diabetic ketoacidosis following PEG-asparaginase therapy

Ahmad, Miriam Hinaa; Shafiq, Ismat

doi:10.1530/edm-18-0064

Cited by 3 publications

(5 citation statements)

References 10 publications

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“…Asparaginase is used commonly in the management of acute lymphoblastic leukemia. Hyperglycemia is common with the use of asparaginase and in pediatric patients with cancer, it varies from 2.5% to 23% [109]. Diazoxide is a potassium channel activator and blocks insulin secretion by opening potassium channels of β cells, resulting in hyperglycemia.…”

Section: Miscellaneous Compoundsmentioning

confidence: 99%

Diabetes and Cancer: Risk, Challenges, Management and Outcomes

Shahid

Ahmed

et al. 2021

Cancers

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Background: Diabetes mellitus and cancer are commonly coexisting illnesses, and the global incidence and prevalence of both are rising. Cancer patients with diabetes face unique challenges. This review highlights the relationship between diabetes and cancer and various aspects of the management of diabetes in cancer patients. Methods: A literature search using keywords in PubMed was performed. Studies that were published in English prior to July 2021 were assessed and an overview of epidemiology, cancer risk, outcomes, treatment-related hyperglycemia and management of diabetes in cancer patients is provided. Results: Overall, 8–18% of cancer patients have diabetes as a comorbid medical condition. Diabetes is a risk factor for certain solid malignancies, such as pancreatic, liver, colon, breast, and endometrial cancer. Several novel targeted compounds and immunotherapies can cause hyperglycemia. Nevertheless, most patients undergoing cancer therapy can be managed with an appropriate glucose lowering agent without the need for discontinuation of cancer treatment. Evidence suggests that cancer patients with diabetes have higher cancer-related mortality; therefore, a multidisciplinary approach is important in the management of patients with diabetes and cancer for a better outcome. Conclusions: Future studies are required to better understand the underlying mechanism between the risk of cancer and diabetes. Furthermore, high-quality prospective studies evaluating management of diabetes in cancer patients using innovative tools are needed. A patient-centered approach is important in cancer patients with diabetes to avoid adverse outcomes.

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Section: Miscellaneous Compoundsmentioning

confidence: 99%

Diabetes and Cancer: Risk, Challenges, Management and Outcomes

Shahid

Ahmed

et al. 2021

Cancers

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“…At present, the mechanism of asparaginase‐associated DKA is still unknown. It is speculated that asparaginase can increase blood sugar and induce DKA by impairing insulin receptor function, increasing insulin resistance, damaging islet β cells, reducing insulin synthesis, and inducing hyperglucagonemia 14,17 …”

Section: Resultsmentioning

confidence: 99%

“…Seven case reports meeting the inclusion criteria were retrieved in PubMed, Embase and Web of Science (One of those case report contained two patients), [8][9][10][11][12][13][14] and a total of eight patient information was collected. The patients were aged between 11 and 25 years old with a median age of 16 years and consist of 4 females and 4 males.…”

Section: Resultsmentioning

confidence: 99%

“…It is speculated that asparaginase can increase blood sugar and induce DKA by impairing insulin receptor function, increasing insulin resistance, damaging islet β cells, reducing insulin synthesis, and inducing hyperglucagonemia. 14,17 In this study, the FAERS system data was used to mine adverse reaction signals by the ROR method. The results showed that L-asp provided a positive pharmacovigilance risk signal, while PEG-asp may not be related to DKA.…”

Section: Discussionmentioning

confidence: 99%

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Asparaginase‐related diabetic ketoacidosis: Analysis of the FDA Adverse Event Reporting System ( FAERS ) data and literature review

Gou

Dong

et al. 2022

Clinical Pharmacy Therapeu

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What is Known and Objective: Diabetic ketoacidosis (DKA) may occur during asparaginase use. However, limited by the study population, the association between asparaginase and DKA has not been elucidated. The purpose of this study was to determine the potential association between asparaginase and DKA and analyse related clinical characteristics and possible risk factor.Methods: Disproportionality analysis with the reporting odd ratio (ROR) was used to detect the adverse reaction signals of asparaginase-associated DKA in Food and Drug Administration Adverse Event Reporting System (FAERS). A literature review was conducted to further analyse clinical characteristics, possible risk factor and something noteworthy in asparaginaseassociated DKA.Results and Discussion: A total of 12 reports of DKA associated with L-asparaginase (L-asp) and 6 reports associated with pegaspargase (PEG-asp) were extracted in FAERS, more than 50% of the cases were classified as serious adverse events. DKA was a positive signal of L-asp (ROR = 2.397, 95% CI 1.360-4.226), while not closely related to the use of PEG-asp (ROR = 1.602, 95% CI 0.719-3.570). Searched in PubMed, Embase and Web of Science, a total of eight patients were collected. The patients were mainly adolescent patients, aged between 11 and 25 years old with a median age of 16 years. Drug dosage form distribution is unbalanced, 7 patients received L-asp and only 1 received PEG-asp.What is New and Conclusions: The ROR of KDA caused by L-asp was statistically significant, but there was not a statistical association for DKA caused by PEG-asp.Asparaginase dosage form may affect the occurrence of DKA, but further research is needed.

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“…Common adverse effects of PEG-asparaginase include hepatotoxicities such as increased AST/ALT and hyperbilirubinemia, hypertriglyceridemia, venous thromboembolism (VTE), and pancreatitis (7,8). While PEG-asparaginase-related pancreatitis has been well characterized, rare cases of additional endocrine complications, including diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS), have been reported (9)(10)(11)(12)(13). Although there have been cases of combined DKA and PEGasparaginase-associated pancreatitis (AAP), the reported case of HHS related to PEG-asparaginase occurred in the absence of AAP.…”

mentioning

confidence: 99%

Case report: Hyperosmolar hyperglycemic syndrome secondary to PEG-asparaginase-induced hypertriglyceridemia and pancreatitis

et al. 2023

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Pegylated (PEG)-asparaginase is an established treatment for acute lymphoblastic leukemias that exhibits an antitumor effect by depleting asparagine, an amino acid essential for leukemia cell protein synthesis. Pancreatitis with hypertriglyceridemia is a well-established toxidrome associated with PEG-asparaginase. However, impaired pancreatic synthetic function and hormone release have rarely been reported as a result of PEG-asparaginase pancreatitis. In this report, we present a 22-year-old woman recently diagnosed with T-acute lymphoblastic leukemia (T-ALL), who presented to the hospital with progressive weakness, confusion, blurry vision, hallucinations, and abdominal pain after induction treatment with daunorubicin, vincristine, PEG-asparaginase, and dexamethasone following the AYA protocol. She was found to have hypertriglyceridemia, acute pancreatitis, and hyperosmolar hyperglycemic syndrome. While pancreatitis and hypertriglyceridemia are commonly reported side effects of PEG-asparaginase, HHS related to these conditions has been sparsely reported. Providers should maintain awareness of this association and consider routine serial glucose monitoring of patients receiving PEG-asparaginase.

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Diabetic ketoacidosis following PEG-asparaginase therapy

Cited by 3 publications

References 10 publications

Diabetes and Cancer: Risk, Challenges, Management and Outcomes

Diabetes and Cancer: Risk, Challenges, Management and Outcomes

Asparaginase‐related diabetic ketoacidosis: Analysis of the FDA Adverse Event Reporting System ( FAERS ) data and literature review

Case report: Hyperosmolar hyperglycemic syndrome secondary to PEG-asparaginase-induced hypertriglyceridemia and pancreatitis

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