Department of Epidemiology and Statistics, School of Public Health, Medical College of Soochow University, Soochow, Jiangsu, China.
Division of non-communicable diseases, Suzhou Industrial Park Centers for Disease Control and Prevention, Soochow, China.
Front Endocrinol (Lausanne). 2023 Jan 19;14:1109747. doi: 10.3389/fendo.2023.1109747. eCollection 2023.
Several cellular and animal studies have suggested that lipoxin A4 (LXA4) has a protective effect on type 2 diabetes mellitus (T2DM) development. However, little is known about whether LXA4 influences T2DM development at the population level.
We included 2755 non-diabetic participants from a cohort study in China who were followed for about seven years. Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for the association between LXA4 and incident T2DM. Mediation models were used to examine how serum lipids as mediators impact the association between LXA4 and T2DM.
In total, 172 newly diagnosed T2DM cases were identified. Multivariate-adjusted HR for T2DM in the fourth compared with the first quartile of LXA4 was 0.62 (95% CI: 0.40-0.96). When used the optimal cutoff value determined by the receiver operating characteristic curve, the results showed participants with LXA4 > 2.84 ng/mL had a decreased T2DM risk compared to those with LXA4 ≤ 2.84 ng/mL (HR: 0.63, 95% CI: 0.45-0.89). The effect of LXA4 on incident T2DM was significantly modified by gender ( = 0.024) and family history of diabetes ( = 0.025). Additionally, the association between LXA4 and incident T2DM was partially suppressed by the TyG and TG/HDL-c ratio, with a suppression proportion of 22.2% and 16.0%, respectively.
Higher LXA4 levels are significantly associated with a lower risk of T2DM development. The present findings would be helpful in understanding the effect of LXA4 on T2DM development at the population level.
多项细胞和动物研究表明，脂氧素 A4（LXA4）对 2 型糖尿病（T2DM）的发展具有保护作用。然而，对于 LXA4 在人群水平上是否影响 T2DM 的发展知之甚少。
我们纳入了中国一项队列研究中的 2755 名非糖尿病参与者，随访时间约为七年。使用 Cox 比例风险模型来估计 LXA4 与 T2DM 发病风险之间的风险比（HR）和 95%置信区间（CI）。使用中介模型来检验血清脂质作为中介物如何影响 LXA4 与 T2DM 之间的关联。
共有 172 例新诊断的 T2DM 病例被确定。LXA4 四分位距第 4 分位与第 1 分位相比，T2DM 的多变量调整 HR 为 0.62（95%CI：0.40-0.96）。当使用由受试者工作特征曲线确定的最佳截断值时，结果显示 LXA4＞2.84ng/mL 的参与者发生 T2DM 的风险较 LXA4≤2.84ng/mL 的参与者降低（HR：0.63，95%CI：0.45-0.89）。LXA4 对 T2DM 发病的影响在性别（ = 0.024）和糖尿病家族史（ = 0.025）方面存在显著的交互作用。此外，LXA4 与 T2DM 发病的关联部分被 TyG 和 TG/HDL-c 比值所抑制，抑制比例分别为 22.2%和 16.0%。
较高的 LXA4 水平与 T2DM 发展风险降低显著相关。本研究结果有助于理解 LXA4 在人群水平上对 T2DM 发展的影响。
