Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study.
Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study.
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DOI：
10.2337/dc18-0884
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发表时间：
2018-11
期刊：
影响因子：
16.2
通讯作者：
Gorden P
中科院分区：
文献类型：
--
作者：
Klubo-Gwiezdzinska J;Lange M;Cochran E;Semple RK;Gewert C;Brown RJ;Gorden P
由于针对胰岛素受体的自身抗体而引起的B型胰岛素抵抗的特征在于对大剂量胰岛素难治的糖尿病、严重的高钙血症、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治疗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，包括确诊为胰岛素受体自身抗体的患者，监测中位数为72个月（第25，75四分位数间距25，88），并接受利妥昔单抗，高剂量脉冲类固醇和环磷酰胺治疗，直到缓解，随后用硫唑嘌呤维持治疗。缓解定义为高血糖改善和胰岛素停药和/或高雄激素血症正常化。所有数据均以中位数（第25、75四分位数间距）表示。22例患者年龄为42（25，57）岁，86.4%为女性，符合入选标准。基线时，空腹血糖为307（203，398）mg/dL，HbA 1c为11.8%（9.7，13.6），总睾酮（女性）为126（57，571）ng/dL（正常8-60），每日胰岛素需求量为1，775（863，2，700）单位。5（4，6.3）个月后，86.4%（19/22）的患者达到缓解，记录为所有患者停用胰岛素，空腹血糖正常80（76，92）mg/dL，HbA 1c为5.5%（5.2，6），睾酮（女性）为28（20，47）ng/dL。在72（25，88）个月的随访中，13.6%（3/22）的患者在初次缓解后24（22，36）个月出现疾病复发，对重复治疗有反应。无患者死亡。联合免疫抑制治疗改变了这种疾病的自然史，从54%的死亡率到糖尿病的可治愈形式，因此，应推荐用于B型胰岛素抵抗患者。
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, HbA1c 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, HbA1c 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.
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影响因子：
5.9
作者：
Furst, Daniel E.;Tseng, Chi-Hong;Schraufnagel, Dean E.
通讯作者：
Schraufnagel, Dean E.
影响因子：
3.3
作者：
Meunier, Godelieve;Ysebaert, Loic;Feugier, Pierre
通讯作者：
Feugier, Pierre
DOI：
10.1038/ncpendmet0693
发表时间：
2007-12-01
期刊：
NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM
影响因子：
--
作者：
Page, Kathleen A.;Dejardin, Stephanie;Inzucchi, Silvio E.
通讯作者：
Inzucchi, Silvio E.
影响因子：
16.2
作者：
Eriksson, JW;Bremell, T;Yu, ZW
通讯作者：
Yu, ZW
影响因子：
3.5
作者：
Iseri, K.;Iyoda, M.;Shibata, T.
通讯作者：
Shibata, T.