{"id":"d66be8445375","type":"article","url":"https://hartvaat.nl/2026/05/25/diabetes-en-calcifierende-aortaklepziekte-gedeelde-immunometabole-pathways-en-th/","title":"Diabetes en calcifiërende aortaklepziekte: gedeelde immunometabole pathways en therapeutische kandidaten","title_en":"","category":"hartfalen","category_label":"Hartfalen","professions":["cardioloog","internist"],"tags":["aortainsufficiëntie","diabetes-en-hart","diabetes-type-1","diabetes-type-2"],"journal":"Cardiovascular diabetology","doi":"10.1186/s12933-026-03219-8","source_url":"https://doi.org/10.1186/s12933-026-03219-8","authors":["Zhang Yue","Qiuchen SiTu","Jin-Hui Bian","Hong-Xiang Lu"],"significance":6,"published":"2026-06-01","source_date":"2026-05-25","image":"https://hartvaat.nl/global/img/fb173d9ccf97.webp","kennis":["https://hartvaat.nl/kennis/farmacologie/sglt2-remmers-farmacologie/","https://hartvaat.nl/kennis/hartfalen/sglt2-remmers-bij-hartfalen/"],"congress":"","summary_en":"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.","created":"2026-07-03T10:32:58Z","updated":"2026-07-03T13:31:53Z","licence":"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.","body_markdown":"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.","abstract_original":"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."}