Rheumatology, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA, USA
Departments of Medicine/Rheumatology and Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
Ann Rheum Dis. 2021 May;80(5):566-572. doi: 10.1136/annrheumdis-2020-219140. Epub 2021 Jan 4.
Rheumatoid arthritis (RA) is associated with a higher risk of diabetes mellitus (DM). Our aim was to determine associations between inflammatory disease activity (including evaluation of specific cytokines and chemokines) and incident DM.
Participants were adults with physician-confirmed RA from Veteran's Affairs Rheumatoid Arthritis Registry. Disease activity and clinical assessments occur longitudinally as part of clinical care. Thirty cytokines and chemokines were measured in banked serum obtained at the time of enrolment. Cytokine/chemokine values were log-adjusted and standardised (per SD). Incident DM was defined based on validated algorithms using diagnostic codes and medications. Multivariable Cox proportional hazard models evaluated associations between clinical factors and incident DM. Independent associations between cytokines/chemokines and incident DM were assessed adjusting for age, sex, race, smoking, body mass index (BMI) and medication use at baseline.
Among 1866 patients with RA without prevalent DM at enrolment, there were 130 incident cases over 9223 person-years of follow-up. High Disease Activity Score (DAS28)-C reactive protein (CRP), obese BMI, older age and male sex were associated with greater risk for incident DM while current smoking and methotrexate use were protective. Patients using methotrexate were at lower risk. Several cytokines/chemokines evaluated were independently associated (per 1 SD) with DM incidence including interleukin(IL)-1, IL-6 and select macrophage-derived cytokines/chemokines (HR range 1.11-1.26). These associations were independent of the DAS28-CRP.
Higher disease activity and elevated levels of cytokines/chemokines are associated with a higher risk of incident DM in patients with RA. Future study may help to determine if targeted treatments in at-risk individuals could prevent the development of DM.
类风湿关节炎（RA）与糖尿病（DM）的风险增加有关。我们的目的是确定炎症性疾病活动（包括特定细胞因子和趋化因子的评估）与新发 DM 之间的关联。
参与者为退伍军人事务部类风湿关节炎登记处确诊的成年 RA 患者。疾病活动和临床评估作为临床护理的一部分进行纵向评估。在登记时采集的储存血清中测量了 30 种细胞因子和趋化因子。细胞因子/趋化因子值经对数调整并标准化（每标准差）。新发 DM 根据使用诊断代码和药物的验证算法定义。多变量 Cox 比例风险模型评估了临床因素与新发 DM 之间的关联。在调整年龄、性别、种族、吸烟、体重指数（BMI）和基线时的药物使用后，评估细胞因子/趋化因子与新发 DM 之间的独立关联。
在 1866 例无 DM 且无 DM 发病的 RA 患者中，在 9223 人年的随访期间发生了 130 例 DM 发病事件。高疾病活动评分（DAS28）-C 反应蛋白（CRP）、肥胖 BMI、年龄较大和男性与更高的 DM 发病风险相关，而当前吸烟和甲氨蝶呤使用具有保护作用。使用甲氨蝶呤的患者风险较低。评估的几种细胞因子/趋化因子与 DM 发病独立相关（每标准差），包括白细胞介素（IL）-1、IL-6 和选择的巨噬细胞衍生细胞因子/趋化因子（HR 范围 1.11-1.26）。这些关联独立于 DAS28-CRP。
在 RA 患者中，更高的疾病活动度和升高的细胞因子/趋化因子水平与新发 DM 的风险增加相关。未来的研究可能有助于确定在高危人群中靶向治疗是否可以预防 DM 的发生。
