New-Onset Post-Transplant Diabetes Mellitus after Allogeneic Hematopoietic Cell Transplant Is Initiated by Insulin Resistance, Not Immunosuppressive Medications
New-Onset Post-Transplant Diabetes Mellitus after Allogeneic Hematopoietic Cell Transplant Is Initiated by Insulin Resistance, Not Immunosuppressive Medications
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DOI：
10.1016/j.bbmt.2019.02.001
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发表时间：
2019-06-01
影响因子：
4.3
通讯作者：
Abumrad, Naji N.
中科院分区：
文献类型：
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作者：
Engelhardt, Brian G.;Savani, Ujjawal;Abumrad, Naji N.
新发移植后糖尿病（PTDM）在异基因造血细胞移植（HO '）后频繁发生。虽然钙调磷酸酶抑制剂和皮质类固醇被认为是高血糖症的原因，但发生PTDM的患者在HO之前和免疫抑制药物之前空腹C肽水平升高。为了确定PTDM是否由移植前存在的胰岛素抵抗引起，我们对20例无移植前糖尿病的患者进行了口服葡萄糖耐量试验（OGTT），并在HLA相同的同胞供体HO'之前和之后90天用正葡萄糖高胰岛素钳夹测量了全身、外周和肝脏的胰岛素敏感性。对HO受体进行前瞻性随访，以确定新发PTDM的发展，新发PTDM定义为每周空腹血糖≥ 126 mg/dL或随机血糖≥ 200 mg/dL。在最初的100天内，所有患者均接受钙调磷酸酶抑制剂治疗，11名患者（55%）被前瞻性诊断为新发PTDM。PTDM诊断先于皮质类固醇治疗。在移植前OGTT期间，空腹血糖水平升高（87 mg/dL vs 101 mg/dL; P= 0.005）但餐后2小时血糖水平不能预测PTDM诊断（P= 0.648）。与非PTDM患者相比，在正常血糖高胰岛素钳夹期间胰岛素输注的反应中，发生PTDM的患者在移植前和移植后分别具有较低的全身葡萄糖利用率（P= 0.047）和外周/骨骼肌摄取率（P= 0.031）。肝脏胰岛素敏感性无差异。PTDM患者的生存率降低（2年估计值，55% vs 100%; P= 0.039）。HO前胰岛素抵抗是PTDM的独立危险因素。移植前空腹血糖水平确定PTDM的易感性，外周胰岛素抵抗可以作为预防和治疗HCT后PTDM的目标。(C)2019年美国血液和骨髓移植协会。爱思唯尔公司出版All rights reserved.
New-onset post-transplant diabetes mellitus (PTDM) occurs frequently after allogeneic hematopoietic cell transplant (HO'). Although calcineurin inhibitors and corticosteroids are assumed to be the cause for hyperglycemia, patients developing PTDM have elevated fasting C-peptide levels before HO' and before immunosuppressive medications. To determine if PTDM results from established insulin resistance present before transplant, we performed oral glucose tolerance tests (OGTTs) and measured whole body, peripheral, and hepatic insulin sensitivity with euglycemic hyperinsulinemic clamps before and 90 days after HLA-identical sibling donor HO' in 20 patients without pretransplant diabetes. HO' recipients were prospectively followed for the development of new-onset PTDM defined as a weekly fasting blood glucose >= 126 mg/dL or random blood glucose >= 200 mg/dL. During the first 100 days all patients received calcineurin inhibitors, and 11 individuals (55%) were prospectively diagnosed with new-onset PTDM. PTDM diagnosis preceded corticosteroid treatment. During the pretransplant OGTT, elevated fasting (87 mg/dL versus 101 mg/dL; P=.005) but not 2-hour postprandial glucose levels predicted PTDM diagnosis (P=.648). In response to insulin infusion during the euglycemic hyperinsulinemic clamp, patients developing PTDM had lower whole body glucose utilization (P=.047) and decreased peripheral/skeletal muscle uptake (P=.031) before and after transplant, respectively, when compared with non-PTDM patients. Hepatic insulin sensitivity did not differ. Survival was decreased in PTDM patients (2-year estimate, 55% versus 100%; P=.039). Insulin resistance before HO' is a risk factor for PTDM independent of immunosuppression. Fasting pretransplant glucose levels identified PTDM susceptibility, and peripheral insulin resistance could be targeted for prevention and treatment of PTDM after HCT. (C) 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.