不同种族群体中糖尿病的患病率及其对多发性骨髓瘤患者生存的影响。
Prevalence and impact of diabetes on survival of patients with multiple myeloma in different racial groups.
发表日期：2023 Sep 29
作者：
Urvi A Shah, Erin Laverne Moshier, Andriy Derkach, Yuanhui Huang, Sham Mailankody, Carlyn Rose Tan, Kylee H Maclachlan, Malin Hultcrantz, Neha Korde, Hani Hassoun, Santiago Thibaud, Larysa Sanchez, Cesar Rodriguez, Shambavi Richard, Joshua Richter, Adriana Rossi, Hearn J Cho, Alexander M Lesokhin, Ajai Chari, Saad Z Usmani, Sundar Jagannath, Samir Parekh, Emily Jane Gallagher
来源：
Blood Advances
摘要：
多发性骨髓瘤（MM）在黑人中的发病率是白人的两倍，而糖尿病（DM）对黑人患者的影响尤为严重。虽然大量研究表明 DM 和 MM 之间存在相关性，但尚未在种族和体内机制的背景下进行研究。我们对 5383 名 MM 患者进行了回顾性临床研究，其中 15% 患有 DM（12% 白人和 25% 黑人）。多变量 Cox 模型显示 DM 患者的总生存期 (OS) 降低（HR 1.27；95% CI 1.11, 1.47；p<0.001）。这似乎是由于患有和不患有糖尿病的白人患者的 OS 存在显着差异，而非黑人患者。相比之下，肥胖与黑人患者更好的 OS 相关，但与白人患者无关。为了补充这一分析，我们评估了基因工程免疫受损的非肥胖糖尿病 (Rag1-/-/MKR) 小鼠模型中 MM 的生长，以评估 DM 和 MM 之间的联系机制。与对照组相比，MM.1S 异种移植物在更多的 Rag1-/-/MKR 小鼠中生长，并且在 Rag1-/-/MKR 小鼠中生长得更快。 Western blot分析发现，来自Rag1-/-/MKR小鼠的MM1.S异种移植物具有较高的磷酸-S6核糖体蛋白(Ser235/236)水平，表明雷帕霉素途径的哺乳动物靶标的激活程度较高。我们的研究首次评估了 DM 患病率和 MM 生存率的种族差异，以及 DM 对小鼠模型肿瘤生长的影响。我们的结果表明，DM 可能导致黑人患者 MM 发病率较高，为了提高 MM 的生存率，DM 管理不容忽视。版权所有 © 2023 美国血液学会。
Multiple myeloma (MM) is twice as common in Black individuals compared to White, and diabetes mellitus (DM) disproportionately affects Black patients. While numerous studies have shown a correlation between DM and MM, this has not been studied in the context of race and in vivo mechanisms. We conducted a retrospective clinical study of 5383 patients with MM of which 15% had DM (12% White and 25% Black). Multivariable Cox models showed reduced overall survival (OS) for patients with DM (HR 1.27; 95% CI 1.11, 1.47; p<0.001). This appeared to be driven by a marked difference in OS between White patients with and without DM, but not Black patients. In contrast, obesity was associated with better OS in Black patients, but not White patients. To complement this analysis, we assessed MM growth in a genetically engineered immunocompromised non-obese diabetic (Rag1-/-/MKR) mouse model to evaluate the mechanisms linking DM and MM. MM.1S xenografts grew in more Rag1-/-/MKR mice and grew more rapidly in the Rag1-/-/MKR mice compared with controls. Western blot analysis found that MM1.S xenografts from Rag1-/-/MKR mice had higher phospho-S6 ribosomal protein(Ser235/236) levels indicating greater activation of the mammalian target of rapamycin pathway. Our study is the first to evaluate racial differences in DM prevalence and survival in MM as well as the effect of DM on tumor growth in mouse models. Our results suggest that DM may contribute to the higher incidence of MM in Black patients, and to improve survival in MM DM management cannot be ignored.Copyright © 2023 American Society of Hematology.