Section of Endocrinology and Metabolism, Department of Internal Medicine, Yale University, New Haven, CT.
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, San Francisco, CA.
Diabetes. 2018 Aug;67(8):1471-1480. doi: 10.2337/dbi18-0002. Epub 2018 Jun 24.
Insulin-dependent diabetes may occur in patients with cancers who are treated with checkpoint inhibitors (CPIs). We reviewed cases occurring over a 6-year period at two academic institutions and identified 27 patients in whom this developed, or an incidence of 0.9%. The patients had a variety of solid-organ cancers, but all had received either anti-PD-1 or anti-PD-L1 antibodies. Diabetes presented with ketoacidosis in 59%, and 42% had evidence of pancreatitis in the peridiagnosis period. Forty percent had at least one positive autoantibody and 21% had two or more. There was a predominance of HLA-DR4, which was present in 76% of patients. Other immune adverse events were seen in 70%, and endocrine adverse events in 44%. We conclude that autoimmune, insulin-dependent diabetes occurs in close to 1% of patients treated with anti-PD-1 or -PD-L1 CPIs. This syndrome has similarities and differences compared with classic type 1 diabetes. The dominance of HLA-DR4 suggests an opportunity to identify those at highest risk of these complications and to discover insights into the mechanisms of this adverse event.
胰岛素依赖型糖尿病可能发生于接受检查点抑制剂 (CPIs) 治疗的癌症患者中。我们回顾了在两个学术机构进行的为期 6 年的病例，发现有 27 例患者发生了这种情况，发病率为 0.9%。这些患者患有各种实体瘤，但均接受了抗 PD-1 或抗 PD-L1 抗体治疗。糖尿病以酮症酸中毒的形式出现，占 59%，42%的患者在诊断前有胰腺炎的证据。40%的患者至少有一种阳性自身抗体，21%的患者有两种或更多种。HLA-DR4 占优势，在 76%的患者中存在。其他免疫不良事件发生率为 70%，内分泌不良事件发生率为 44%。我们得出结论，接受抗 PD-1 或抗 PD-L1 CPIs 治疗的患者中，约有 1%会发生自身免疫性、胰岛素依赖型糖尿病。这种综合征与经典的 1 型糖尿病既有相似之处，也有不同之处。HLA-DR4 的优势表明有机会识别出那些处于发生这些并发症的最高风险的患者，并发现对这种不良事件的机制的见解。
