TY - JOUR
T1 - Type 2 diabetes and depression via microvascular dysfunction, neurodegeneration, inflammation, advanced glycation end products (AGEs), and arterial stiffness
AU - Steens, Indra L. M.
AU - Schram, Miranda T.
AU - Houben, Alfons J. H. M.
AU - Berendschot, Tos T. J. M.
AU - Koster, Annemarie
AU - Bosma, Hans
AU - Eussen, Simone J. P. M.
AU - de Galan, Bastiaan E.
AU - van Sloten, Thomas T.
PY - 2025/9
Y1 - 2025/9
N2 - Aims 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. Materials and Methods 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). Results 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. Conclusions 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.
AB - Aims 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. Materials and Methods 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). Results 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. Conclusions 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.
KW - cardiovascular disease
KW - diabetes complications
KW - population study
KW - type 2 diabetes
KW - ASSOCIATION
KW - DISEASE
KW - SYMPTOMS
KW - COMPLICATIONS
KW - PREVALENCE
KW - CALIBER
KW - RISK
U2 - 10.1111/dom.16527
DO - 10.1111/dom.16527
M3 - Article
SN - 1462-8902
VL - 27
SP - 4847
EP - 4858
JO - Diabetes Obesity & Metabolism
JF - Diabetes Obesity & Metabolism
IS - 9
M1 - 16527
ER -