Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou, 215123, P. R. China.
Section of Pulmonary and Critical Care Medicine, Medical Service, Providence VA Medical Center, Providence, RI 02908, USA.
J Clin Endocrinol Metab. 2023 Aug 18;108(9):e769-e778. doi: 10.1210/clinem/dgad140.
Whether baseline preserved ratio impaired spirometry (PRISm) is associated with the risk of developing type 2 diabetes (T2D) and if this association could be mediated by circulating metabolites remains to be elucidated.
To measure the prospective association of PRISm with T2D and potential metabolic mediators thereof.
This study used data from the UK Biobank and included 72 683 individuals without diabetes at baseline. PRISm was defined as the predicted forced expiratory volume in 1 second (FEV1) <80% and the FEV1/forced vital capacity ratio ≥0.70. Cox proportional hazards modeling was performed to assess the longitudinal relation between baseline PRISm and incident T2D. Mediation analysis was used to explore the mediation effects of circulating metabolites in the path from PRISm to T2D.
During a median follow-up of 12.06 years, 2513 participants developed T2D. Individuals who had PRISm (N = 8394) were 47% (95% CI, 33%-63%) more likely to develop T2D compared with those who had normal spirometry (N = 64 289). A total of 121 metabolites showed statistically significant mediation effects in the path from PRISm to T2D (false discovery rate <0.05). Glycoprotein acetyls, cholesteryl esters in large high-density lipoprotein (HDL), degree of unsaturation, cholesterol in large HDL, and cholesteryl esters in very large HDL were the top 5 metabolic markers, with mediation proportions (95% CI) being 11.91% (8.76%-16.58%), 11.04% (7.34%-15.55%), 10.36% (7.34%-14.71%), 9.87% (6.78%-14.09%), and 9.51% (6.33%-14.05%), respectively. A total of 11 principal components that explained 95% variance of the metabolic signatures accounted for 25.47% (20.83%-32.19%) of the relation between PRISm and T2D.
Our study revealed the association of PRISm with T2D risk and the potential roles of circulating metabolites in mediating this association.
基线保留比受损的肺活量测定法（PRISm）是否与 2 型糖尿病（T2D）的发病风险相关，以及这种关联是否可以通过循环代谢物来介导，仍有待阐明。
测量 PRISm 与 T2D 的前瞻性关联及其潜在的代谢介导物。
本研究使用了英国生物库的数据，共纳入了 72683 名基线时无糖尿病的个体。PRISm 的定义为预测的 1 秒用力呼气量（FEV1）<80%和 FEV1/用力肺活量比≥0.70。采用 Cox 比例风险模型评估基线 PRISm 与新发 T2D 之间的纵向关系。采用中介分析探索 PRISm 与 T2D 之间路径中循环代谢物的中介作用。
在中位随访 12.06 年期间，有 2513 名参与者发生了 T2D。与正常肺活量测定法（N=64289）相比，有 PRISm（N=8394）的个体发生 T2D 的可能性高 47%（95%CI，33%-63%）。共有 121 种代谢物在 PRISm 与 T2D 之间的路径中表现出统计学上显著的中介作用（错误发现率<0.05）。糖蛋白乙酰基、大高密度脂蛋白（HDL）中的胆甾醇酯、不饱和程度、大 HDL 中的胆固醇和非常大 HDL 中的胆甾醇酯是前 5 种代谢标志物，其中介比例（95%CI）分别为 11.91%（8.76%-16.58%）、11.04%（7.34%-15.55%）、10.36%（7.34%-14.71%）、9.87%（6.78%-14.09%）和 9.51%（6.33%-14.05%）。解释代谢特征 95%方差的 11 个主成分占 PRISm 与 T2D 之间关系的 25.47%（20.83%-32.19%）。
本研究揭示了 PRISm 与 T2D 风险的关联，以及循环代谢物在介导这种关联中的潜在作用。
