# The impact of glucose and metabolic disturbances on white matter hyperintensity volume in apparently healthy adults

**Authors:** Aleksandra Szum-Jakubowska, Marlena Dubatówka, Małgorzata Chlabicz, Jacek Jamiołkowski, Marcin Hładuński, Alexander Teumer, Katharina Wittfeld, Mikołaj A. Pawlak, Irina Kowalska, Karol A. Kamiński

PMC · DOI: 10.3389/fendo.2026.1789777 · Frontiers in Endocrinology · 2026-03-18

## TL;DR

This study shows that glucose metabolism issues, even before full diabetes, are linked to brain changes visible on MRI scans in otherwise healthy adults.

## Contribution

The study identifies prediabetes and metabolic disturbances as novel risk factors for white matter hyperintensities in a healthy population.

## Key findings

- Glucose metabolism disorders are associated with increased white matter hyperintensity volume.
- Prediabetes with both impaired glucose tolerance and fasting glucose is linked to larger WMH volumes.
- Managing metabolic risk factors may help reduce cognitive decline risk.

## Abstract

White matter hyperintensities (WMHs), commonly seen in brain magnetic resonance imaging (MRI), are linked to cognitive decline and may be influenced by cardiovascular risk factors. This study explores the relationship between diabetes, prediabetes, metabolic syndrome, and the presence of WMHs in an apparently healthy population.

The study group includes 735 adult participants without neurological or severe cardiovascular diseases. During the visit, participants took part in detailed clinical examination (medical history, biochemical analysis, carotid arteries ultrasound, and brain MRI). WMHs were quantified by the SAMSEG tool implemented in Freesurfer software.

Participants’ median age was 45 (range, 36–58) years, 341 (46.39%) were men, 58 (7.9%) had diagnosed diabetes, 345 (46.94%) had diagnosed prediabetes, and 91 (12.38%) individuals fulfilled two definitions of prediabetes—simultaneously impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Univariate analysis presented a positive association between plasma glucose concentrations, glycated hemoglobin, diabetes mellitus, prediabetes, and metabolic syndrome and WMHs (p < 0.05). Multivariate analysis (R2adj. = 0.33) presented an association between glucose metabolism disorders (diabetes mellitus or fulfilling two definitions of prediabetes, β = 2.77, p = 0.006) and WMHs.

Patients with glucose metabolism disorders, not only those with diabetes but also those fulfilling definitions of prediabetes IGT and IFG simultaneously, have significantly larger volumes of WMHs. Patients with diabetes or prediabetes may benefit from the comprehensive management of cardiovascular risk factors, not only to limit the risk of cardiovascular disease but also to potentially reduce the risk of cognitive impairment.

## Linked entities

- **Diseases:** diabetes mellitus (MONDO:0005015), prediabetes (MONDO:0006920), metabolic syndrome (MONDO:0000816)

## Full-text entities

- **Diseases:** glucose metabolism disorders (MESH:D044882), IFG (MESH:D007003), metabolic disturbances (MESH:D024821), prediabetes (MESH:D011236), WMHs (MESH:D056784), diabetes (MESH:D003920), cardiovascular disease (MESH:D002318), IGT (MESH:D018149), cognitive decline (MESH:D003072)
- **Chemicals:** glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13038537/full.md

## References

24 references — full list in the complete paper: https://tomesphere.com/paper/PMC13038537/full.md

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Source: https://tomesphere.com/paper/PMC13038537