获得性全身性脂肪营养不良：抗 PD-1 免疫相关糖尿病的一个新病因。
Acquired Generalized Lipodystrophy: A New Cause of Anti-PD-1 Immune-Related Diabetes.
机构信息
French Network of Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS) and FIRENDO Network, Paris and Lyon, France.
Endocrinology, Diabetology, and Nutrition Department, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.
出版信息
Diabetes Care. 2019 Oct;42(10):2008-2010. doi: 10.2337/dc18-2535. Epub 2019 Aug 21.
OBJECTIVE
Anti-programmed cell death-1 (anti-PD-1) antibodies have revolutionized advanced cancer therapy. Anti-PD-1 therapy is responsible for immune-related adverse events, with frequent endocrine manifestations, including acute-onset type 1 diabetes. Acquired generalized lipodystrophy (AGL) is a rare disease, believed to be immune mediated, characterized by loss of adipose tissue and insulin resistance-associated complications.
RESEARCH DESIGN AND METHODS
We describe the first reported case of AGL induced by immune checkpoint therapy.
RESULTS
A 62-year-old woman with metastatic melanoma treated with nivolumab was referred for major hyperglycemia, hypertriglyceridemia, and nonalcoholic steatohepatitis. She had presented with a rapidly progressive generalized loss of subcutaneous adipose tissue. Diabetes was associated with severe insulin resistance and undetectable plasma leptin. Subcutaneous biopsy revealed atrophic adipose tissue infiltrated with cytotoxic CD8 T lymphocytes and fibrosis.
CONCLUSIONS
AGL is an additional immune-related adverse event of anti-PD-1 therapy that leads to severe insulin resistance-associated complications.
目的
抗程序性细胞死亡蛋白-1（抗 PD-1）抗体彻底改变了晚期癌症的治疗方法。抗 PD-1 治疗会引起免疫相关不良反应，常表现为内分泌系统症状，包括急性发作 1 型糖尿病。获得性全身性脂肪营养不良（AGL）是一种罕见疾病，被认为与免疫有关，其特征是脂肪组织丧失和与胰岛素抵抗相关的并发症。
研究设计与方法
我们描述了首例由免疫检查点治疗引起的 AGL 病例。
结果
一名 62 岁的转移性黑色素瘤女性患者接受了 nivolumab 治疗，因严重高血糖、高三酰甘油血症和非酒精性脂肪性肝炎而就诊。她迅速出现全身皮下脂肪丧失。糖尿病与严重胰岛素抵抗和不可检测的血浆瘦素有关。皮下活检显示脂肪组织萎缩，浸润着细胞毒性 CD8 T 淋巴细胞和纤维化。
结论
AGL 是抗 PD-1 治疗的另一种免疫相关不良反应，可导致严重的与胰岛素抵抗相关的并发症。
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