Department of Diabetes, Endocrinology and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, USA.
Inflammation. 2013 Feb;36(1):177-85. doi: 10.1007/s10753-012-9533-7.
Stress hyperglycemia and acute graft-versus-host disease (GVHD), the major early complication of hematopoietic stem cell transplantation (HSCT), are both associated with excessive release of inflammatory cytokines. We investigated whether new-onset hyperglycemia immediately after HSCT predicts acute GVHD. We studied nondiabetic adult recipients of human leukocyte antigen-matched HSCT (peripheral blood stem cells) for acute leukemia. Using mean morning serum glucose on Days 1-10, we classified hyperglycemia as: mild (6.11-8.33 mmol/L), moderate (8.34-9.98), and severe (minimum of 9.99). Subjects who were GVHD-free on Day 10 were followed during Days 11-100 for grades II-IV acute GVHD or competing event. Evaluation utilized cumulative incidence-based proportional hazards regression. Subjects (n = 328) were age 18-74, median of 49 years. Per body mass index (BMI)--25.0 % were obese (BMI, 30-48), 33.8 % overweight (25 to <30), 30.8 % normal weight (21 to <25), and 10.4 % lean (18 to <21). Mild, moderate, or severe hyperglycemia occurred during Days 1-10 in 50.0, 21.3, and 16.8 % of subjects, respectively. Cumulative incidence on Day 100 was 44.8 (±2.8) % acute GVHD and 7.9 (±1.5) % competing event. Among normal-to-overweight subjects (n = 212), severe hyperglycemia developed in 14.2 % (n = 30) and more than doubled the risk of acute GVHD (hazards ratio, 2.71; 95 % CI, 1.58-4.65--adjusted for donor/recipient characteristics, prophylactic regimen, and mucositis). In contrast, among obese subjects (n = 82), severe hyperglycemia developed in 30.5 % (n = 25) but did not significantly affect risk of GVHD. (No lean subjects (n = 34) developed severe hyperglycemia.) Hyperglycemia that was less than severe had an effect indistinguishable from normoglycemia. In nondiabetic patients, severe hyperglycemia immediately after allogeneic HSCT indicates increased likelihood of acute GVHD. This association is absent in obese patients, who may be primed by obesity-induced inflammation to develop severe hyperglycemia even without experiencing the cytokine storm that is essential to GVHD pathogenesis.
应激性高血糖和急性移植物抗宿主病（GVHD）是造血干细胞移植（HSCT）的主要早期并发症，均与炎症细胞因子的过度释放有关。我们研究了 HSCT 后即刻发生的新发高血糖是否可预测急性 GVHD。我们研究了接受 HLA 匹配的 HSCT（外周血干细胞）治疗的非糖尿病成人急性白血病患者。根据第 1-10 天早晨的平均血清葡萄糖水平，我们将高血糖分为：轻度（6.11-8.33mmol/L）、中度（8.34-9.98mmol/L）和重度（至少 9.99mmol/L）。第 10 天无急性 GVHD 的患者在第 11-100 天期间接受 II-IV 级急性 GVHD 或竞争事件的随访。评估采用累积发生率基于比例风险回归。受试者（n=328）年龄 18-74 岁，中位数为 49 岁。按体重指数（BMI）划分-25.0%为肥胖（BMI，30-48），33.8%为超重（25-<30），30.8%为正常体重（21-<25），10.4%为消瘦（18-<21）。轻度、中度或重度高血糖分别发生在 50.0%、21.3%和 16.8%的患者中。第 100 天的累积发生率为 44.8（±2.8）%的急性 GVHD 和 7.9（±1.5）%的竞争事件。在正常体重到超重患者（n=212）中，重度高血糖发生在 14.2%（n=30），急性 GVHD 的风险增加了两倍以上（风险比，2.71；95%CI，1.58-4.65--调整供体/受体特征、预防方案和黏膜炎）。相比之下，在肥胖患者（n=82）中，重度高血糖发生在 30.5%（n=25），但对 GVHD 风险无显著影响。（无消瘦患者（n=34）发生重度高血糖。）程度较轻的高血糖与正常血糖的作用没有区别。在非糖尿病患者中，HSCT 后严重高血糖提示急性 GVHD 的可能性增加。这种关联在肥胖患者中不存在，肥胖患者可能因肥胖引起的炎症而发生重度高血糖，即使没有经历对 GVHD 发病机制至关重要的细胞因子风暴。
