Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Biol Blood Marrow Transplant. 2019 Jun;25(6):1225-1231. doi: 10.1016/j.bbmt.2019.02.001. Epub 2019 Feb 7.
New-onset post-transplant diabetes mellitus (PTDM) occurs frequently after allogeneic hematopoietic cell transplant (HCT). Although calcineurin inhibitors and corticosteroids are assumed to be the cause for hyperglycemia, patients developing PTDM have elevated fasting C-peptide levels before HCT 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 HCT in 20 patients without pretransplant diabetes. HCT 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 HCT 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.
异基因造血细胞移植（HCT）后常发生新发移植后糖尿病（PTDM）。尽管钙调神经磷酸酶抑制剂和皮质类固醇被认为是导致高血糖的原因，但在 HCT 前和免疫抑制药物治疗前，发生 PTDM 的患者空腹 C 肽水平升高。为了确定 PTDM 是否是移植前存在的已确立的胰岛素抵抗引起的，我们在 20 例无移植前糖尿病的 HLA 匹配同胞供体 HCT 前和 90 天后进行了口服葡萄糖耐量试验（OGTT），并使用正葡萄糖高胰岛素钳夹测量了全身、外周和肝胰岛素敏感性。HCT 受者前瞻性随访以确定新诊断的 PTDM，定义为每周空腹血糖≥126mg/dL 或随机血糖≥200mg/dL。在前 100 天，所有患者均接受钙调神经磷酸酶抑制剂治疗，11 例（55%）患者被前瞻性诊断为新发 PTDM。PTDM 的诊断先于皮质类固醇治疗。在移植前 OGTT 中，空腹（87mg/dL 比 101mg/dL；P=0.005）但餐后 2 小时血糖水平升高预测 PTDM 诊断（P=0.648）。在正葡萄糖高胰岛素钳夹期间，与非 PTDM 患者相比，发生 PTDM 的患者在移植前后的全身葡萄糖利用率（P=0.047）和外周/骨骼肌摄取率（P=0.031）降低。肝胰岛素敏感性无差异。PTDM 患者的生存率降低（2 年估计，55%比 100%；P=0.039）。HCT 前的胰岛素抵抗是独立于免疫抑制的 PTDM 的危险因素。移植前空腹血糖水平可识别 PTDM 易感性，外周胰岛素抵抗可能成为预防和治疗 HCT 后 PTDM 的靶点。
