Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study.
Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study.
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作者：
Carstensen M;Herder C;Kivimäki M;Jokela M;Roden M;Shipley MJ;Witte DR;Brunner EJ;Tabák AG
尽管白细胞介素-1受体拮抗剂（IL-1 Ra）治疗与2型糖尿病患者β细胞功能改善和血糖控制相关，但其在2型糖尿病发展中的作用仍不清楚。我们使用重复测量来表征2型糖尿病患者的IL-1 Ra轨迹。这项病例队列研究嵌套在白厅II队列中，基于335例2型糖尿病病例和2，475例非病例。我们测量了每个个体最多三个时间点的血清IL-1 Ra水平，并使用多水平分析估计了糖尿病诊断前（病例受试者）或随访结束时（对照受试者）的IL-1 Ra回顾性轨迹。根据年龄、性别和种族调整模型。在糖尿病诊断/随访结束前13年，病例组的IL-1 Ra水平已经高于对照组受试者（平均值[95% CI] 302 [290-314] vs. 244 [238-249] pg/ml）。在对照受试者中，IL-1 Ra水平在整个研究期间显示出适度的线性增加。在病例受试者中，IL-1 Ra的轨迹与对照受试者平行，直到诊断前6年（95%CI 7.5-4.5），然后在诊断时急剧上升至399（379-420）pg/ml（斜率差异P < 0.0001）。调整BMI和腰围作为随时间变化的协变量对这些轨迹的影响很小。我们发现IL-1 Ra水平升高了13年，在2型糖尿病诊断前的最后6年中加速增加，表明存在抗炎反应，可能有助于平衡2型糖尿病之前的代谢和免疫紊乱。
Although interleukin-1 receptor antagonist (IL-1Ra) treatment is associated with improved β-cell function and glycemic control in patients with type 2 diabetes, its role in the development of type 2 diabetes remains unclear. We used repeated measurements to characterize IL-1Ra trajectories in individuals who developed type 2 diabetes. This case-cohort study, nested within the Whitehall II cohort, was based on 335 incident type 2 diabetes cases and 2,475 noncases. We measured serum IL-1Ra levels at up to three time points per individual and estimated retrospective trajectories of IL-1Ra before diabetes diagnosis (case subjects) or end of follow-up (control subjects) using multilevel analysis. Models were adjusted for age, sex, and ethnicity. IL-1Ra levels were already higher in the case than control subjects 13 years before diabetes diagnosis/end of follow-up (mean [95% CI] 302 [290–314] vs. 244 [238–249] pg/ml). In control subjects, IL-1Ra levels showed a modest linear increase throughout the study period. In case subjects, IL-1Ra trajectories were parallel to those in control subjects until 6 years (95% CI 7.5–4.5) before diagnosis and then rose steeply to 399 (379–420) pg/ml at the time of diagnosis (P < 0.0001 for slope difference). Adjustment for BMI and waist circumference as time-varying covariates had little impact on these trajectories. We show elevated IL-1Ra levels for 13 years and an accelerated increase during the last 6 years before type 2 diabetes diagnosis, indicating the presence of an anti-inflammatory response that may act to counterbalance the metabolic and immunologic disturbances that precede type 2 diabetes.
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影响因子：
16.2
作者：
Herder C;Brunner EJ;Rathmann W;Strassburger K;Tabák AG;Schloot NC;Witte DR
通讯作者：
Witte DR
影响因子：
7.7
作者：
Juge-Aubry, CE;Somm, E;Meier, CA
通讯作者：
Meier, CA
影响因子：
7.7
作者：
Butler, AE;Janson, J;Butler, PC
通讯作者：
Butler, PC
影响因子：
4.4
作者：
Cartier, Amelie;Bergeron, Jean;Despres, Jean-Pierre
通讯作者：
Despres, Jean-Pierre
影响因子：
8.2
作者：
Herder, C;Baumert, J;Kolb, H
通讯作者：
Kolb, H