ArticleCardiovascular diabetology2025
Pseudohypoxia caused by germline genetic alterations in the VHL gene is associated with increased diabetes and cardiovascular risk: a UK biobank study.
Article in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVon Hippel-Lindau protein deficiency leads to cellular and tissue false sense of hypoxia (pseudohypoxia), driving erythropoiesis, angiogenesis, and dysglycemia. The impact of partial VHL protein deficiency, caused by heterozygous VHL gene alterations on diabetes and cardiovascular risk has not been investigated. Hence, in the current study we assessed a possible association between VHL genotype and cardiovascular risk based on a the UK Biobank genomic and clinical data.
methodsDemographic, clinical and biochemical data were extracted, and exome analysis, focusing on the VHL gene locus was performed for all patients (n = 460,430). Variant severity was sub-categorized into low (5'- and 3'-untranslated region (UTR)), medium (missense, in-frame indels), and high-risk (nonsense, splice-site, and frameshift). Metabolic and cardiovascular outcomes were compared between VHL variant carriers vs. non-carriers.
resultsVHL gene variant carriers (n = 2516) had an increased risk of diabetes (p = 0.04) and cerebrovascular accidents (CVA, p = 0.03) vs. controls, more pronounced in higher severity variants. 5'UTR variants were associated with an increased risk of diabetes (p < 0.001) and a younger age at diabetes diagnosis (p = 0.003) compared to other variants. In multivariable analysis, 5'UTR variants were associated with an increased risk of diabetes (odds ratio 2.97, 95% confidence interval 1.78-4.80, p < 0.001). Increasing reticulocyte levels positively correlated with metabolic syndrome markers (serum glucose, glycated hemoglobin, and triglyceride levels) and mediated the increased diabetes risk of 5'UTR variant carriers.
conclusionsVHL gene variant carriers have an increased risk of diabetes and CVA. Mediation analysis suggests pseudohypoxia as a possible mechanism.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.