Manikas Emmanouil-Dimitrios, Isaac Iona, Semple Robert K, Malek Rana, Führer Dagmar, Moeller Lars C
University Duisburg-Essen (E.-D.M., D.F., L.C.M.), Department of Endocrinology and Metabolism and Division of Laboratory Research, 45147 Essen, Germany; Wellcome Trust-Medical Research Council Institute of Metabolic Science (I.I., R.K.S.), Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; and University of Maryland School of Medicine (R.M.), Division of Endocrinology, Diabetes, and Nutrition, Baltimore, Maryland 21201.
J Clin Endocrinol Metab. 2015 May;100(5):1719-22. doi: 10.1210/jc.2014-3552. Epub 2015 Feb 12.
Type B insulin resistance is a very rare disease caused by autoantibodies against the insulin receptor. The mortality of type B insulin resistance is high (>50%), and management of this disease is not yet standardized. We report the successful treatment of a patient with type B insulin resistance with rituximab, cyclophosphamide, and prednisone.
A 45-year-old woman presented with unintended weight loss of 20 kg, unusually widespread acanthosis nigricans, and glucose levels > 500 mg/dL, which could not be controlled with up to 600 IU/d of insulin. Because of the severity of the insulin resistance combined with features of insulin deficiency, type B insulin resistance was suspected. Detection of high levels of insulin receptor autoantibodies confirmed the diagnosis. Neither immunosuppressive therapy with Ig iv nor plasmapheresis had an effect on glucose levels or insulin dose. Because the patient's condition was deteriorating, we started rituximab (750 mg/m(2) in two doses 2 wk apart) together with cyclophosphamide (100 mg/d orally) and dexamethasone 40 mg/d for 4 days. Two months after initiation of rituximab therapy, fasting glucose levels ranged from 80 to 110 mg/dL and could be controlled with very low insulin doses. Glycated hemoglobin decreased from 11.8 to 6.5%. Two months later, insulin therapy was stopped, and the patient showed normal blood glucose readings.
In this patient with type B insulin resistance, Ig treatment and plasmapheresis failed to improve the condition. Finally, treatment with rituximab, cyclophosphamide, and steroids was successful in inducing a complete remission.
B型胰岛素抵抗是一种由抗胰岛素受体自身抗体引起的极为罕见的疾病。B型胰岛素抵抗的死亡率很高（>50%），且该疾病的治疗尚未标准化。我们报告了1例使用利妥昔单抗、环磷酰胺和泼尼松成功治疗B型胰岛素抵抗患者的病例。
一名45岁女性出现意外体重减轻20 kg、异常广泛的黑棘皮病以及血糖水平>500 mg/dL，使用高达600 IU/d的胰岛素也无法控制。由于胰岛素抵抗严重并伴有胰岛素缺乏特征，怀疑为B型胰岛素抵抗。检测到高水平的胰岛素受体自身抗体确诊了该诊断。静脉注射免疫球蛋白（Ig）或血浆置换的免疫抑制治疗对血糖水平或胰岛素剂量均无效果。由于患者病情恶化，我们开始使用利妥昔单抗（750 mg/m²，分2剂，间隔2周），同时口服环磷酰胺（100 mg/d）和地塞米松40 mg/d，共4天。利妥昔单抗治疗开始2个月后，空腹血糖水平在80至110 mg/dL之间，可用极低剂量胰岛素控制。糖化血红蛋白从11.8%降至6.5%。2个月后，停止胰岛素治疗，患者血糖读数正常。
在该B型胰岛素抵抗患者中，Ig治疗和血浆置换未能改善病情。最终，利妥昔单抗、环磷酰胺和类固醇治疗成功诱导了完全缓解。
