Loke Michael, Sehgal Vishal, Gupta Niraj
Ascension St. Vincent Internal Medicine, Indianapolis, Indiana.
Ascension St. Vincent Endocrinology, Indianapolis, Indiana.
AACE Clin Case Rep. 2024 Oct 18;11(1):40-44. doi: 10.1016/j.aace.2024.10.002. eCollection 2025 Jan-Feb.
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.
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.
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.
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.
背景/目的：阿哌利西布是一种磷脂酰肌醇3激酶抑制剂，用于治疗某些对激素疗法耐药的乳腺癌，它可通过抑制胰岛素信号级联反应导致高血糖。阿哌利西布起始治疗时引发糖尿病酮症酸中毒仍然是一种罕见的并发症。本报告的目的是描述一例发生阿哌利西布诱导的糖尿病酮症酸中毒的患者及其管理难点。
一名59岁女性因2型非胰岛素依赖型糖尿病病史服用二甲双胍，因糖尿病酮症酸中毒入院。此次住院前一个月，该患者开始服用阿哌利西布。就诊时，血糖水平为612mg/dL，糖化血红蛋白水平为11.9%（107mmol/mol），较2个月前升高了4.6%（27mmol/mol）。患者开始接受静脉胰岛素治疗，停用阿哌利西布后，高血糖和酮症酸中毒迅速缓解。然而，重新开始使用阿哌利西布后，患者的高血糖情况恶化。最终通过3种口服药物和高剂量胰岛素实现了相对血糖控制。
阿哌利西布直接抑制胰岛素信号会导致胰岛素抵抗性高血糖。大多数病例可用口服药物控制；然而，在罕见情况下需要胰岛素治疗。尽管胰岛素治疗对血糖控制更有效，但它有可能降低阿哌利西布的抗肿瘤作用。
糖尿病酮症酸中毒是阿哌利西布起始治疗时的罕见并发症，停用该药物后可迅速缓解。对于无法停用该药物的患者，可使用胰岛素和胰岛素增敏剂来实现血糖控制，但可能会对肿瘤治疗产生不利影响。
