Metabolic Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow, U.K.
Diabetes Care. 2018 Nov;41(11):2353-2360. doi: 10.2337/dc18-0884. Epub 2018 Sep 10.
Type B insulin resistance due to autoantibodies against the insulin receptor is characterized by diabetes refractory to massive doses of insulin, severe hypercatabolism, hyperandrogenism, and a high mortality rate. We analyzed the efficacy of combined immunosuppressive therapy in the management of this extreme form of diabetes.
We performed a prospective cohort study including patients with confirmed insulin receptor autoantibodies, monitored for median 72 months (25th, 75th interquartile range 25, 88), and treated with rituximab, high-dose pulsed steroids, and cyclophosphamide until remission, followed by maintenance therapy with azathioprine. Remission was defined as the amelioration of the hyperglycemia and discontinuation of insulin and/or normalization of hyperandrogenemia.
All data are given as median (25th, 75th interquartile range). Twenty-two patients aged 42 (25, 57) years, 86.4% women, fulfilled inclusion criteria. At baseline, fasting glucose was 307 (203, 398) mg/dL, HbA was 11.8% (9.7, 13.6), total testosterone (women) was 126 (57, 571) ng/dL (normal 8-60), and daily insulin requirement was 1,775 (863, 2,700) units. After 5 (4, 6.3) months, 86.4% (19 of 22) of patients achieved remission, documented by discontinuation of insulin in all patients, normal fasting glucose of 80 (76, 92) mg/dL, HbA of 5.5% (5.2, 6), and testosterone (women) of 28 (20, 47) ng/dL. During follow-up of 72 (25, 88) months, 13.6% (3 of 22) of patients developed disease recurrence, occurring 24 (22, 36) months after initial remission, which responded to repeated therapy. None of the patients died.
Combined immunosuppressive therapy has changed the natural history of this disease, from 54% mortality to a curable form of diabetes and, as such, should be recommended in patients with type B insulin resistance.
由于针对胰岛素受体的自身抗体引起的 B 型胰岛素抵抗的特征是对大剂量胰岛素具有抗性的糖尿病、严重的高分解代谢、高雄激素血症和高死亡率。我们分析了联合免疫抑制疗法在管理这种极端形式的糖尿病中的疗效。
我们进行了一项前瞻性队列研究，纳入了已确诊的胰岛素受体自身抗体患者，中位随访时间为 72 个月（25%、75%四分位间距 25、88），并接受利妥昔单抗、大剂量脉冲类固醇和环磷酰胺治疗，直至缓解，然后用硫唑嘌呤维持治疗。缓解定义为改善高血糖和停止使用胰岛素和/或恢复正常的高雄激素血症。
所有数据均以中位数（25%、75%四分位间距）表示。22 名年龄为 42（25、57）岁、86.4%为女性的患者符合纳入标准。基线时，空腹血糖为 307（203、398）mg/dL，HbA1c 为 11.8%（9.7、13.6），总睾酮（女性）为 126（57、571）ng/dL（正常值 8-60），每日胰岛素需求量为 1775（863、2700）单位。5（4、6.3）个月后，86.4%（22 例中的 19 例）的患者达到缓解，所有患者均停止使用胰岛素，空腹血糖正常为 80（76、92）mg/dL，HbA1c 为 5.5%（5.2、6），睾酮（女性）为 28（20、47）ng/dL。在 72（25、88）个月的随访期间，13.6%（22 例中的 3 例）的患者出现疾病复发，复发发生在初始缓解后 24（22、36）个月，再次治疗后有效。无患者死亡。
联合免疫抑制疗法改变了这种疾病的自然病程，从 54%的死亡率变为可治愈的糖尿病形式，因此应推荐给 B 型胰岛素抵抗患者。
