Hyperglycemia secondary to phosphatidylinositol-3 kinase (PI3K) inhibition.

IF 0.7 Q4 ENDOCRINOLOGY & METABOLISM
Arunan Sriravindrarajah, Joshua Hurwitz, Elgene Lim, Jerry R Greenfield
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引用次数: 0

Abstract

Summary: Phosphatidylinositol-3 kinase (PI3K) is a critical intracellular pathway that regulates cell growth, metabolism, and survival and has been implicated in most human cancers. Targeting this pathway has been approved as a therapeutic option for breast cancer and lymphoma (e.g. alpelisib, idelalisib), and there are several clinical trials underway in additional types of cancer. However, PI3K is an important mediator of the action of insulin, and the use of PI3K inhibitors has been associated with hyperglycemia. We report the case of a 53-year-old female with metastatic breast cancer who developed acute grade 3 hyperglycemia from a novel PI3K inhibitor, inavolisib. We review the treatment options for PI3K inhibitor-associated hyperglycemia. Treatment strategies that minimize hyperinsulinemia may be preferable considering animal models have demonstrated that hyperinsulinemia may result in partial reactivation of the PI3K pathway and counter the anti-cancer effectiveness of PI3K inhibitors.

Learning points: Phosphatidylinositol-3 kinase (PI3K) is an intracellular pathway that regulates a range of physiological functions, including cell growth, metabolism, survival, and angiogenesis. Hyperactivation of the PI3K pathway is associated with almost all human cancers, and thus PI3K inhibition has been proposed as a treatment option for selected cancers. The action of insulin after binding to the insulin receptor on the cell surface (e.g. glucose uptake in skeletal muscle, inhibition of glycogenolysis and gluconeogenesis) is mediated by the intracellular PI3K pathway, and thus PI3K inhibition may lead to hyperinsulinemic hyperglycemia. All patients treated with PI3K inhibitors should receive pre-treatment screening for hyperglycemia, lifestyle advice, and a glucometer to measure fasting BGL and 2-h post-dinner BGL levels twice per week for at least the first 30 days of treatment. Insulin or insulin secretagogues (e.g. sulfonylurea) may inhibit the anti-tumor activity of PI3K inhibitors, and thus treatment of PI3K inhibitor-associated hyperglycemia should prefer alternative approaches such as a low carbohydrate diet, metformin, SGLT2i, or dose reduction of the PI3K inhibitor.

继发于磷脂酰肌醇-3 激酶(PI3K)抑制的高血糖。
摘要:磷脂酰肌醇-3 激酶(PI3K)是调节细胞生长、新陈代谢和存活的重要细胞内通路,与大多数人类癌症有关。靶向这一通路已被批准作为乳腺癌和淋巴瘤的治疗选择(如阿昔替尼、idelalisib),目前还有几项针对其他类型癌症的临床试验正在进行中。然而,PI3K 是胰岛素作用的重要介质,使用 PI3K 抑制剂与高血糖有关。我们报告了一例 53 岁女性转移性乳腺癌患者因服用新型 PI3K 抑制剂 inavolisib 而出现急性 3 级高血糖的病例。我们回顾了 PI3K 抑制剂相关高血糖症的治疗方案。考虑到动物模型已证明高胰岛素血症可能会导致PI3K通路的部分再激活,并抵消PI3K抑制剂的抗癌效果,因此尽量减少高胰岛素血症的治疗策略可能更可取:磷脂酰肌醇-3 激酶(PI3K)是一种细胞内通路,可调节一系列生理功能,包括细胞生长、新陈代谢、存活和血管生成。几乎所有人类癌症都与 PI3K 通路的过度激活有关,因此有人提出将抑制 PI3K 作为治疗某些癌症的一种选择。胰岛素与细胞表面的胰岛素受体结合后的作用(如骨骼肌中的葡萄糖摄取、糖原分解和葡萄糖生成的抑制)是由细胞内的 PI3K 途径介导的,因此 PI3K 抑制可能会导致高胰岛素血症性高血糖。所有接受 PI3K 抑制剂治疗的患者都应在治疗前接受高血糖筛查、生活方式建议,并在治疗的最初 30 天内至少每周两次使用血糖仪测量空腹血糖生成水平和餐后 2 小时血糖生成水平。胰岛素或胰岛素促泌剂(如磺脲类药物)可能会抑制 PI3K 抑制剂的抗肿瘤活性,因此治疗 PI3K 抑制剂相关高血糖症应首选低碳水化合物饮食、二甲双胍、SGLT2i 或减少 PI3K 抑制剂剂量等替代方法。
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来源期刊
CiteScore
1.50
自引率
0.00%
发文量
142
审稿时长
9 weeks
期刊介绍: Endocrinology, Diabetes & Metabolism Case Reports publishes case reports on common and rare conditions in all areas of clinical endocrinology, diabetes and metabolism. Articles should include clear learning points which readers can use to inform medical education or clinical practice. The types of cases of interest to Endocrinology, Diabetes & Metabolism Case Reports include: -Insight into disease pathogenesis or mechanism of therapy - Novel diagnostic procedure - Novel treatment - Unique/unexpected symptoms or presentations of a disease - New disease or syndrome: presentations/diagnosis/management - Unusual effects of medical treatment - Error in diagnosis/pitfalls and caveats
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