Steens Indra L M, Schram Miranda T, Houben Alfons J H M, Berendschot Tos T J M, Jansen Jacobus F A, Backes Walter H, Koster Annemarie, Bosma Hans, Eussen Simone J P M, de Galan Bastiaan E, van Sloten Thomas T
CARIM Cardiovascular Research Institute Maastricht, Maastricht University (UM), Maastricht, The Netherlands.
Department of Internal Medicine, Maastricht University Medical Center+ (MUMC+), Maastricht, The Netherlands.
Diabetes Obes Metab. 2025 Sep;27(9):4847-4858. doi: 10.1111/dom.16527. Epub 2025 Jun 19.
Type 2 diabetes increases the risk of depression, but the mechanisms underlying this association are incompletely understood. We investigated whether microvascular dysfunction, neurodegeneration, low-grade inflammation, advanced glycation end products (AGEs) and arterial stiffness, pathologies that are more common in diabetes, explain, or mediate the association between type 2 diabetes and incident clinically relevant depressive symptoms.
We used prospective data from The Maastricht Study, a population-based cohort study. Diabetes status and potential mediators were assessed at baseline. Clinically relevant depressive symptoms (PHQ-9 score ≥10) were assessed at baseline and each year during a median of 8.1 (IQR 4.2, 10.1) years of follow-up. Mediation analysis was employed to investigate the mediating effect of microvascular dysfunction (retinal, blood and MRI biomarkers), neurodegeneration (retina and MRI biomarkers), low-grade inflammation (blood biomarkers), AGEs (skin and blood biomarkers) and arterial stiffness (tonometry and ultrasound biomarkers).
Data of 6091 participants (age, 59.4 years [SD 8.6]; 51.3% women; 23.6% type 2 diabetes) were available. Type 2 diabetes was associated with a higher incidence of clinically relevant depressive symptoms (HR:1.37; 95% CI 1.13, 1.65). This association was partly mediated by microvascular dysfunction (proportion mediated:10.4% [95% CI:3.6%, 17.2%]); neurodegeneration (proportion mediated:12.1% [95% CI: 3.9%, 20.3%]); AGEs (proportion mediated:5.4% [95% CI: 3.0%, 8.8%]); and arterial stiffness (proportion mediated:8.4% [95% CI: 3.3%, 13.5%]); but not by low-grade inflammation.
The association between type 2 diabetes and a higher risk of clinically relevant depressive symptoms is partly mediated by microvascular dysfunction, neurodegeneration, AGEs and arterial stiffness.
2型糖尿病会增加患抑郁症的风险，但其潜在机制尚未完全明确。我们研究了微血管功能障碍、神经退行性变、低度炎症、晚期糖基化终末产物（AGEs）和动脉僵硬度（这些病症在糖尿病中更为常见）是否能解释或介导2型糖尿病与临床相关抑郁症状之间的关联。
我们使用了基于人群的队列研究——马斯特里赫特研究的前瞻性数据。在基线时评估糖尿病状态和潜在的中介因素。在基线时以及随访的中位数8.1（四分位间距4.2，10.1）年期间每年评估临床相关抑郁症状（PHQ - 9评分≥10）。采用中介分析来研究微血管功能障碍（视网膜、血液和磁共振成像生物标志物）、神经退行性变（视网膜和磁共振成像生物标志物）、低度炎症（血液生物标志物）、AGEs（皮肤和血液生物标志物）和动脉僵硬度（眼压测量和超声生物标志物）的中介作用。
共有6091名参与者的数据（年龄，59.4岁[标准差8.6]；51.3%为女性；23.6%患有2型糖尿病）可供分析。2型糖尿病与临床相关抑郁症状的较高发病率相关（风险比：1.37；95%置信区间1.13，1.65）。这种关联部分由微血管功能障碍介导（介导比例：10.4%[95%置信区间：3.6%，17.2%]）；神经退行性变（介导比例：12.1%[95%置信区间：3.9%，20.3%]）；AGEs（介导比例：5.4%[95%置信区间：3.0%，8.8%]）；以及动脉僵硬度（介导比例：8.4%[95%置信区间：3.3%，13.5%]）；但不是由低度炎症介导。
2型糖尿病与临床相关抑郁症状较高风险之间的关联部分由微血管功能障碍、神经退行性变、AGEs和动脉僵硬度介导。
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