Imagawa Akihisa, Tachibana Megumi
Department of Internal Medicine (I), Osaka Medical College, 2-7 Daigaku-cho, Takatsuki, 569-8686 Japan.
Diabetol Int. 2020 Sep 16;11(4):336-341. doi: 10.1007/s13340-020-00466-2. eCollection 2020 Oct.
To clarify the clinical and etiological characteristics of fulminant type 1 diabetes, we reviewed data from patients who had developed type 1 diabetes following anti-programmed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) therapy, and research on pancreatic beta cells derived from induced pluripotent stem (iPS) cells from patients with fulminant type 1 diabetes. As determined from the disease classifications and clinical and genetic characteristics, anti-PD-1/PD-L1 therapy-related type 1 diabetes includes both fulminant type 1 diabetes and acute-onset type 1 diabetes. Using insulin-positive cells derived from iPS cells, beta-cell fragility to inflammatory cytokines, but not its regeneration failure, was observed in fulminant type 1 diabetes. Moreover, severe hyperglycemia was reported as a risk factor of sudden death or cardiac arrest at disease onset, diffusion-weighted magnetic resonance imaging was suggested as an additional tool for making a diagnosis, and the locus was genetically associated with fulminant type 1 diabetes. To fully understand fulminant type 1 diabetes, it is important to clarify the molecular mechanisms step by step through multifaceted approaches such as through analyses of the genetic factors, clinical features, histological findings, and cell biology. The careful and detailed study of patients is a great means for clarifying the etiology and pathophysiology of the disease.
为阐明暴发性1型糖尿病的临床和病因学特征，我们回顾了接受抗程序性细胞死亡蛋白1/程序性细胞死亡配体1（抗PD-1/PD-L1）治疗后发生1型糖尿病的患者的数据，以及对暴发性1型糖尿病患者诱导多能干细胞（iPS细胞）来源的胰腺β细胞的研究。根据疾病分类以及临床和遗传特征确定，抗PD-1/PD-L1治疗相关的1型糖尿病包括暴发性1型糖尿病和急性起病型1型糖尿病。在暴发性1型糖尿病中，利用iPS细胞来源的胰岛素阳性细胞，观察到β细胞对炎性细胞因子的脆弱性，但未观察到其再生失败。此外，严重高血糖被报道为疾病发作时猝死或心脏骤停的危险因素，扩散加权磁共振成像被建议作为一种辅助诊断工具，并且该位点与暴发性1型糖尿病存在遗传关联。为全面了解暴发性1型糖尿病，通过多方面的方法逐步阐明分子机制很重要，例如通过分析遗传因素、临床特征、组织学发现和细胞生物学。对患者进行仔细和详细的研究是阐明该疾病病因和病理生理学的重要手段。
