# Diabetes en calcifiërende aortaklepziekte: gedeelde immunometabole pathways en therapeutische kandidaten

*geplaatst 2026-06-01 · Hartfalen · Cardiovascular diabetology · doi 10.1186/s12933-026-03219-8 · https://hartvaat.nl/2026/05/25/diabetes-en-calcifierende-aortaklepziekte-gedeelde-immunometabole-pathways-en-th/*

Review van de immunometabole mechanismen die diabetes mellitus verbinden met versneld calcifiërende aortaklepziekte (CAVD). Diabetes verhoogt consistent het risico op aortastenose (HR 1,3-1,7), de calcificatielast en de ziekte-ernst, onafhankelijk van klassieke risicofactoren. De auteurs schetsen zeven overlappende pathways: fenotypische omschakeling van valvulaire interstitiële cellen door hyperglykemie en insulineresistentie, AGE-RAGE-signalering, oxidatieve stress, NLRP3-IL-1β-inflammasoom-activatie, endotheeldysfunctie, BMP-Runx2-Wnt-Notch osteogene reprogrammering, en kruisbestuiving tussen CKD en mineralocorticoïdreceptor. Metformine, SGLT2-remmers, IL-1β/NLRP3-remmers en Lp(a)-verlagende strategieën worden voorgedragen als kandidaten voor klinische evaluatie. Het kader pleit voor specifiek op diabetische CAVD gerichte gerandomiseerde studies.

## English: 

Review of the immunometabolic mechanisms linking diabetes mellitus to accelerated calcific aortic valve disease (CAVD). Diabetes consistently increases incident aortic stenosis risk (HR 1.3-1.7), calcification burden and disease severity, independent of traditional risk factors. The authors delineate seven overlapping pathways: valvular interstitial cell phenotypic switching driven by hyperglycaemia and insulin resistance, AGE-RAGE signalling, oxidative stress, NLRP3-IL-1β inflammasome activation, endothelial dysfunction, BMP-Runx2-Wnt-Notch osteogenic reprogramming, and CKD-mineralocorticoid receptor cross-talk. Metformin, SGLT2 inhibitors, IL-1β/NLRP3 inhibitors and Lp(a)-lowering strategies are proposed candidates for clinical evaluation. The framework argues for valve-focused randomised trials in diabetic CAVD.

## Abstract (original, from the publication)

This review synthesizes the immunometabolic mechanisms linking diabetes mellitus to accelerated calcific aortic valve disease (CAVD) and evaluates their therapeutic implications. Despite the absence of disease-modifying pharmacotherapy for CAVD, diabetes consistently increases incident aortic stenosis risk (HR 1.3-1.7), calcification burden, and disease severity, independent of traditional cardiovascular risk factors. Epidemiological, imaging, and histological evidence demonstrate that dysglycemia promotes earlier onset, denser valvular calcium deposits, and worse post-intervention outcomes. We delineate seven interconnected and partially overlapping pathways through which diabetes remodels the aortic valve: hyperglycemia-driven valvular interstitial cell (VIC) phenotypic switching and insulin resistance; advanced glycation end-product-RAGE signaling; oxidative stress and mitochondrial dysfunction; macrophage NLRP3-IL-1β inflammasome activation; endothelial barrier compromise; BMP-Runx2-Wnt-Notch osteogenic reprogramming; and CKD-mineralocorticoid receptor cross-talk. These processes convert metabolic stress into sustained valvular inflammation, matrix remodeling, and ectopic ossification. Mechanistic and observational data provide a rationale for evaluating metformin, SGLT2 inhibitors, IL-1β/NLRP3 inhibitors, and Lp(a)-lowering strategies as candidate approaches to modulate calcification progression. Integrated metabolic-inflammatory-imaging biomarkers offer potential for risk stratification and trial enrichment. This immunometabolic framework identifies actionable nodes and underscores the urgent need for dedicated, valve-focused randomized trials in diabetic CAVD to translate mechanistic insights into clinical benefit.

Auteurs: Zhang Yue, Qiuchen SiTu, Jin-Hui Bian, Hong-Xiang Lu

---
Bron: Cardiovascular diabetology, https://doi.org/10.1186/s12933-026-03219-8. Bijgewerkt 2026-07-03T13:31:53Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.