Alpelisib-Induced Diabetic Ketoacidosis and Insulin-Resistant Hyperglycemia
Background/Objective: Alpelisib is a phosphatidylinositol 3-kinase inhibitor used to treat certain hormone therapy resistant breast cancers that can cause hyperglycemia through inhibition of the insulin signaling cascade. Diabetic ketoacidosis with the initiation of alpelisib remains a rare complica...
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Elsevier
2025-01-01
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| Series: | AACE Clinical Case Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2376060524001111 |
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| author | Michael Loke, DO Vishal Sehgal, MD Niraj Gupta, MD |
| author_facet | Michael Loke, DO Vishal Sehgal, MD Niraj Gupta, MD |
| author_sort | Michael Loke, DO |
| collection | DOAJ |
| description | Background/Objective: Alpelisib is a phosphatidylinositol 3-kinase inhibitor used to treat certain hormone therapy resistant breast cancers that can cause hyperglycemia through inhibition of the insulin signaling cascade. Diabetic ketoacidosis with the initiation of alpelisib remains a rare complication. The objective of this report is to describe a patient with alpelisib-induced diabetic ketoacidosis and the difficulties of management. Case Report: A 59-year-old woman was admitted to the hospital with a history of noninsulin dependent type 2 diabetes on metformin presented with diabetic ketoacidosis. One month prior to this hospitalization, the patient was started on alpelisib. On presentation, blood glucose level was 612 mg/dL and hemoglobin A1c level was 11.9% (107 mmol/mol), a 4.6% (27 mmol/mol) increase from 2 months prior. The patient was started on intravenous insulin and alpelisib was held resulting in rapid resolution of the patient’s hyperglycemia and ketoacidosis. However, with reinitiation of alpelisib the patient developed worsening hyperglycemia. Relative glycemic control was ultimately obtained with 3 oral agents and high doses of insulin. Discussion: Direct inhibition of insulin signaling by alpelisib leads to insulin-resistant hyperglycemia. Most cases can be controlled with oral agents; however, insulin therapy is required in rare instances. Although more effective for glycemic control, insulin therapy has the potential to decrease the antitumor effects of alpelisib. Conclusion: Diabetic ketoacidosis is a rare complication of alpelisib initiation, which is quickly resolved with cessation of the agent. For patients where cessation is not an option, insulin and insulin sensitizing agents can be used to achieve glycemic control at the potential detriment of tumor treatment. |
| format | Article |
| id | doaj-art-9966219ac88241709156373868cc619d |
| institution | Kabale University |
| issn | 2376-0605 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | AACE Clinical Case Reports |
| spelling | doaj-art-9966219ac88241709156373868cc619d2025-01-15T04:11:45ZengElsevierAACE Clinical Case Reports2376-06052025-01-011114044Alpelisib-Induced Diabetic Ketoacidosis and Insulin-Resistant HyperglycemiaMichael Loke, DO0Vishal Sehgal, MD1Niraj Gupta, MD2Ascension St. Vincent Internal Medicine, Indianapolis, Indiana; Address correspondence to Dr Michael Loke, Ascension St. Vincent Internal Medicine, 8414 Naab Rd, Indianapolis, IN 46260.Ascension St. Vincent Endocrinology, Indianapolis, IndianaAscension St. Vincent Hematology and Oncology, Indianapolis, IndianaBackground/Objective: Alpelisib is a phosphatidylinositol 3-kinase inhibitor used to treat certain hormone therapy resistant breast cancers that can cause hyperglycemia through inhibition of the insulin signaling cascade. Diabetic ketoacidosis with the initiation of alpelisib remains a rare complication. The objective of this report is to describe a patient with alpelisib-induced diabetic ketoacidosis and the difficulties of management. Case Report: A 59-year-old woman was admitted to the hospital with a history of noninsulin dependent type 2 diabetes on metformin presented with diabetic ketoacidosis. One month prior to this hospitalization, the patient was started on alpelisib. On presentation, blood glucose level was 612 mg/dL and hemoglobin A1c level was 11.9% (107 mmol/mol), a 4.6% (27 mmol/mol) increase from 2 months prior. The patient was started on intravenous insulin and alpelisib was held resulting in rapid resolution of the patient’s hyperglycemia and ketoacidosis. However, with reinitiation of alpelisib the patient developed worsening hyperglycemia. Relative glycemic control was ultimately obtained with 3 oral agents and high doses of insulin. Discussion: Direct inhibition of insulin signaling by alpelisib leads to insulin-resistant hyperglycemia. Most cases can be controlled with oral agents; however, insulin therapy is required in rare instances. Although more effective for glycemic control, insulin therapy has the potential to decrease the antitumor effects of alpelisib. Conclusion: Diabetic ketoacidosis is a rare complication of alpelisib initiation, which is quickly resolved with cessation of the agent. For patients where cessation is not an option, insulin and insulin sensitizing agents can be used to achieve glycemic control at the potential detriment of tumor treatment.http://www.sciencedirect.com/science/article/pii/S2376060524001111alpelisibdiabetic ketoacidosisPI3K inhibitorresistant hyperglycemia |
| spellingShingle | Michael Loke, DO Vishal Sehgal, MD Niraj Gupta, MD Alpelisib-Induced Diabetic Ketoacidosis and Insulin-Resistant Hyperglycemia AACE Clinical Case Reports alpelisib diabetic ketoacidosis PI3K inhibitor resistant hyperglycemia |
| title | Alpelisib-Induced Diabetic Ketoacidosis and Insulin-Resistant Hyperglycemia |
| title_full | Alpelisib-Induced Diabetic Ketoacidosis and Insulin-Resistant Hyperglycemia |
| title_fullStr | Alpelisib-Induced Diabetic Ketoacidosis and Insulin-Resistant Hyperglycemia |
| title_full_unstemmed | Alpelisib-Induced Diabetic Ketoacidosis and Insulin-Resistant Hyperglycemia |
| title_short | Alpelisib-Induced Diabetic Ketoacidosis and Insulin-Resistant Hyperglycemia |
| title_sort | alpelisib induced diabetic ketoacidosis and insulin resistant hyperglycemia |
| topic | alpelisib diabetic ketoacidosis PI3K inhibitor resistant hyperglycemia |
| url | http://www.sciencedirect.com/science/article/pii/S2376060524001111 |
| work_keys_str_mv | AT michaellokedo alpelisibinduceddiabeticketoacidosisandinsulinresistanthyperglycemia AT vishalsehgalmd alpelisibinduceddiabeticketoacidosisandinsulinresistanthyperglycemia AT nirajguptamd alpelisibinduceddiabeticketoacidosisandinsulinresistanthyperglycemia |