Bowman Christopher, Abramson Vandana, Wellons Melissa
Vanderbilt University Medical Center, Nashville, TN, USA.
J Investig Med High Impact Case Rep. 2017 Aug 23;5(3):2324709617725351. doi: 10.1177/2324709617725351. eCollection 2017 Jul-Sep.
. Many phosphoinositide-3-kinase (PI3K) inhibitors are under trial for cancer treatment. We present a patient taking taselisib who developed ketoacidosis within 1 week of starting canagliflozin. . A 69-year-old female patient with no previous history of diabetes mellitus was enrolled in a clinical trial for taselisib therapy in stage IV breast cancer. Hyperglycemia treatment with metformin was insufficient and not tolerated. The addition of canagliflozin daily resulted in ketoacidosis and hospitalization within 1 week. . This case report brings together 2 poorly understood and relatively understudied disorders of glucose homeostasis: hyperglycemia due to PI3K inhibition and euglycemic ketoacidosis due to dehydration/SGLT2 inhibition. It demonstrates the complexities of glucose management in the setting of PI3K inhibition. PI3K stimulation (via insulin) in this setting is counterintuitive; therefore, non-insulin-mediated therapies (eg, metformin, thiazolidinediones) might be favored over insulin-mediated therapies.
许多磷酸肌醇-3-激酶(PI3K)抑制剂正在进行癌症治疗试验。我们报告了一名服用塔西利西布的患者,在开始服用卡格列净后1周内发生了酮症酸中毒。一名69岁的女性患者,既往无糖尿病病史,参加了一项针对IV期乳腺癌的塔西利西布治疗的临床试验。使用二甲双胍治疗高血糖效果不佳且患者不耐受。每天加用卡格列净导致1周内发生酮症酸中毒并住院。本病例报告汇集了2种对葡萄糖稳态了解甚少且研究相对不足的疾病:PI3K抑制导致的高血糖和脱水/钠-葡萄糖协同转运蛋白2(SGLT2)抑制导致的正常血糖性酮症酸中毒。它证明了在PI3K抑制情况下葡萄糖管理的复杂性。在这种情况下,PI3K刺激(通过胰岛素)是违反直觉的;因此,非胰岛素介导的治疗(如二甲双胍、噻唑烷二酮类)可能比胰岛素介导的治疗更受青睐。