ArticleCardiovascular diabetology2020
Accumulation of advanced glycation end products (AGEs) is associated with the severity of aortic stenosis in patients with concomitant type 2 diabetes.
Article in Cardiovascular diabetology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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46 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Association between the soluble receptor for advanced glycation end products and diabetes mellitus: systematic review and meta-analysis.BMC endocrine disorders · 2024Pooled it
- Type 2 diabetes is associated with clinical progression of aortic stenosis: a nationwide retrospective study in Sweden.Scientific reports · 2026Article
- Emerging Role of Sodium-Glucose Cotransporter-2 Inhibitors in Aortic Stenosis.JACC. Basic to translational science · 2026Review
- Shared pathophysiological mechanisms between diabetes and calcific aortic valve disease: an immunometabolic perspective.Cardiovascular diabetology · 2026Review
- The AGE-RAGE Pathway in Endometriosis: A Focused Mechanistic Review and Structured Evidence Map.International journal of molecular sciences · 2026Review
- Concentration of Trace Elements in Patients with Aortic Stenosis and Coexisting Coronary Artery Disease: A Pilot Study.Journal of clinical medicine · 2025Article
- Article
- Beneficial Effects of Grape Pomace Extract on Hyperglycemia, Dyslipidemia, and Oxidative Stress in Experimental Diabetes Mellitus.Molecules (Basel, Switzerland) · 2025Article
- Association between cholesterol, high-density lipoprotein, and glucose index and risks of cardiovascular and all-cause mortality in patients with calcific aortic valve stenosis: the ARISTOTLE cohort study.Cardiovascular diabetology · 2025Observational
- Decoding the regulatory role of noncoding RNAs in biological and vascular calcification.Molecular biology reports · 2025Review
- The Influence of Diabetes Mellitus and Kidney Dysfunction on Oxidative Stress, a Reflection of the Multisystem Interactions in Aortic Stenosis.Antioxidants (Basel, Switzerland) · 2025Article
- Dysglycaemia and incident aortic stenosis: a cohort study.Heart (British Cardiac Society) · 2025Article
- Dysglycaemia is associated with the pattern of valvular calcification in micro-computed tomography analysis: an observational study in patients with severe aortic stenosis.Cardiovascular diabetology · 2025Observational
- Aortic valve calcification across stages of dysglycemia in middle-aged individuals from the general population.Cardiovascular diabetology · 2025Article
- Protocatechualdehyde attenuates oxidative stress in diabetic cataract via GLO1-mediated inhibition of AGE/RAGE glycosylation.Frontiers in pharmacology · 2025Article
- The roles of advanced glycation end products in cardiovascular diseases: from mechanisms to therapeutic strategies.Frontiers in cardiovascular medicine · 2025Review
- Diabetes and calcific aortic valve disease: controversy of clinical outcomes in diabetes after aortic valve replacement.Frontiers in endocrinology · 2025Review
- "Hyperglycemic Memory": Observational Evidence to Experimental Inference.Current diabetes reviews · 2025Review
- Diabetes and calcific aortic valve disease: implications of glucose-lowering medication as potential therapy.Frontiers in pharmacology · 2025Review
- Mechanism of traditional Chinese medicine in elderly diabetes mellitus and a systematic review of its clinical application.Frontiers in pharmacology · 2024Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAccumulation of advanced glycation end products (AGEs) leads to chronic glycation of proteins and tissue damage, particularly in patients with diabetes mellitus (DM). We aimed to evaluate whether increased accumulation of AGEs in patients with aortic stenosis (AS) and concomitant type 2 diabetes (DM) is associated with AS severity.
methodsWe prospectively enrolled 76 patients with severe AS (47.1% males; nonDM), aged 68 [66-72] years, and 50 age-matched DM patients with a median blood glucose level of 7.5 [5.9-9.1] mM and glycated hemoglobin (HbA1c) of 6.8 [6.3-7.8]%, scheduled for aortic valve replacement. Valvular expression of AGEs, AGEs receptor (RAGE), interleukin-6 (IL-6), and reactive oxygen species (ROS) induction were evaluated ex vivo by immunostaining and calculated as the extent of positive immunoreactive areas/total sample area. Plasma levels of AGEs and soluble RAGE (sRAGE) were assessed by ELISAs.
resultsSubjects with DM had increased valvular expression of both AGEs (6.6-fold higher, 15.53 [9.96-23.28]%) and RAGE (1.8-fold higher, 6.8 [4.9-8.45]%) compared to nonDM patients (2.05 [1.21-2.58]% and 2.4 [1.56-3.02]%, respectively; both p < 0.001). Plasma levels of AGEs (12-fold higher) and sRAGE (1.3-fold higher) were elevated in DM patients, compared to nonDM (both p < 0.0001). The percentage of valvular ROS-positive (2.28 [1.6-3.09] vs. 1.15 [0.94-1.4]%, p < 0.0001) but not IL-6-positive areas was higher within DM, compared to nonDM valves. In DM patients, the percentage of valvular AGEs- and RAGE-positive areas correlated with HbA1c (r = 0.77, p < 0.0001 and r = 0.30, p = 0.034). Similarly, plasma AGEs and sRAGE levels were associated with HbA1c in the DM group (r = 0.32, p = 0.024 and r = 0.33, p = 0.014, respectively). In all DM patients, we found an association between the amount of valvular AGEs and the disease severity measured as aortic valve area (AVA; r = 0.68, p < 0.0001). Additionally, in DM patients with HbA1c > 7% (n = 24, 48%) we found that valvular expression of AGEs correlated with mean transvalvular pressure gradient (PG
conclusionsOur study suggests that poorly-controlled diabetes leads to increased AGEs and RAGE valvular accumulation, which at least partially, might result in AS progression in DM patients.
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