Obata Yoshinari, Takayama Kana, Nishikubo Hideyuki, Tobimatsu Aoki, Matsuda Izumi, Uehara Yuhei, Maruo Yumiko, Sho Hiroyuki, Kosugi Motohiro, Yasuda Tetsuyuki
Department of Diabetes and Endocrinology, Osaka Police Hospital, 10-31 Kitayama-cho, Tennojiku, Osaka 543-0035 Japan.
Diabetol Int. 2022 Dec 24;14(2):211-216. doi: 10.1007/s13340-022-00611-z. eCollection 2023 Apr.
Exogenous insulin can induce insulin antibodies that have a low affinity/high binding capacity. Similar to what is observed in insulin autoimmune syndrome, these insulin antibodies can cause fasting hypoglycemia and postprandial hyperglycemia, a phenomenon known as "exogenous insulin antibody syndrome" (EIAS). Cases of EIAS in patients with type 1 and type 2 diabetes have been sporadically reported, mainly in Asia. However, there has been no report on EIAS in patients with diabetes secondary to total pancreatectomy treated with insulin analogs. A 74-year-old man with diabetes after total pancreatectomy had been treated with continuous subcutaneous insulin infusion using an insulin analog, lispro, and developed recurrent early morning hypoglycemia even after discontinuation of nocturnal basal insulin. His fasting serum lispro level was high even approximately 9 h after the last lispro dose. He had a high titer (72.7%) of insulin antibodies, and a Scatchard analysis revealed low affinity/high binding capacity. These findings suggested that the patient's recurrent early morning hypoglycemia was associated with insulin antibodies against lispro, and we, therefore, switched from lispro to another insulin analog, glulisine. His hypoglycemia improved, accompanied by a dramatic decrease in his insulin antibodies and serum glulisine levels. Early morning hypoglycemia in patients with diabetes secondary to total pancreatectomy may often be explained by high glycemic variability, malnutrition, and/or glucagon deficiency. However, in cases of recurrent early morning hypoglycemia, EIAS should be considered as a potential differential diagnosis.
外源性胰岛素可诱导产生低亲和力/高结合能力的胰岛素抗体。与胰岛素自身免疫综合征中观察到的情况类似,这些胰岛素抗体可导致空腹低血糖和餐后高血糖,这一现象被称为“外源性胰岛素抗体综合征”(EIAS)。1型和2型糖尿病患者中EIAS的病例已有零星报道,主要在亚洲。然而,对于接受胰岛素类似物治疗的全胰腺切除术后继发糖尿病的患者,尚无关于EIAS的报道。一名74岁的全胰腺切除术后糖尿病男性患者,使用胰岛素类似物赖脯胰岛素进行持续皮下胰岛素输注治疗,即使停用夜间基础胰岛素后仍反复出现清晨低血糖。即使在最后一剂赖脯胰岛素给药约9小时后,他的空腹血清赖脯胰岛素水平仍很高。他的胰岛素抗体滴度很高(72.7%),Scatchard分析显示为低亲和力/高结合能力。这些发现表明,患者反复出现的清晨低血糖与针对赖脯胰岛素的胰岛素抗体有关,因此,我们将治疗从赖脯胰岛素改为另一种胰岛素类似物门冬胰岛素。他的低血糖情况得到改善,同时胰岛素抗体和血清门冬胰岛素水平显著下降。全胰腺切除术后继发糖尿病患者的清晨低血糖通常可能由高血糖变异性、营养不良和/或胰高血糖素缺乏来解释。然而,对于反复出现清晨低血糖的病例,应考虑EIAS作为一种潜在的鉴别诊断。