Insulin resistance and brain sulcal morphology in non-diabetic adults.
6 affiliations
- 1Division of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan.
- 2National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
- 3Department of Radiology, Tokyo Medical University, Tokyo, Japan.
- 4Department of Neurology, The Jikei University School of Medicine, Tokyo, Japan.
- 5Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan.
- 6Institute of Systems and Information Engineering, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Abstract
Insulin resistance exerts direct effects on brain structure, yet most neuroimaging evidence comes from populations with established diabetes, and conventional gray matter volumetry may lack sensitivity to detect early structural changes. Here, we examined associations between insulin resistance and sulcal morphology, a measure that integrates cortical thinning, subcortical atrophy, and white matter degeneration into a single outcome, in 728 non-diabetic adults (518 men, 210 women; mean age 61.4 ± 11.6 years). Brain volumes were quantified using OpenMAP-T1, an automated deep learning-based parcellation tool, and associations between HOMA-IR and 30 cerebrospinal fluid-related regional volumes were examined using multiple linear regression adjusted for age, sex, and estimated total intracranial volume, with FDR correction for multiple comparisons. Higher HOMA-IR was significantly associated with greater frontal sulcal volumes (left: β = 596 mm³, right: β = 344 mm³; both FDR-corrected p < 0.001), with a dose-response relationship across insulin resistance categories. This association was observed only in men (sex × HOMA-IR interaction p = 0.019) and was strongest in participants younger than 70 years. Mediation analysis revealed that the relationship between BMI and frontal sulcal enlargement was largely accounted for by the indirect pathway through insulin resistance, with no significant direct effect of BMI. These findings suggest that sulcal morphology can detect metabolic effects on brain structure at a pre-diabetic stage, changes that were not apparent through frontal gray matter volumetry in the same sample, and identify insulin resistance as a potential modifiable target for preserving brain health.
Related
- Amelioration of chronic inflammation, insulin resistance, and gut microbiota homeostasis by a combination of Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus in obese type 2 diabetic mice
- The diabetic interstitium as an overlooked layer of insulin resistance: vascular delivery, tissue transport, and insulin clearance
- Association and discriminative value of insulin resistance surrogate markers for aortic stiffness in asymptomatic adults
- Correlation Between Neck Circumference and Insulin Resistance in Apparently Healthy Adults
- Interaction of sex and insulin resistance with cognitive impairment in community-dwelling middle-aged and older adults
BibTeX
@article{yoshimaru2026insulin,
title = {{Insulin resistance and brain sulcal morphology in non-diabetic adults.}},
author = {Daisuke Yoshimaru and Ami Yuzawa and Masakazu Ozawa and Motoki Hirabayashi and Yutaka Matsushita and Tomokazu Tsurugizawa and Hirotaka James Okano},
journal = {Imaging neuroscience (Cambridge, Mass.)},
year = {2026},
month = oct,
doi = {10.1162/imag.a.1402},
url = {https://europepmc.org/article/MED/42903296},
note = {CC BY},
}
RIS
TY - JOUR
TI - Insulin resistance and brain sulcal morphology in non-diabetic adults.
AU - Daisuke Yoshimaru
AU - Ami Yuzawa
AU - Masakazu Ozawa
AU - Motoki Hirabayashi
AU - Yutaka Matsushita
AU - Tomokazu Tsurugizawa
AU - Hirotaka James Okano
PY - 2026
DA - 2026/10/16
JO - Imaging neuroscience (Cambridge, Mass.)
DO - 10.1162/imag.a.1402
UR - https://europepmc.org/article/MED/42903296
AB - Insulin resistance exerts direct effects on brain structure, yet most neuroimaging evidence comes from populations with established diabetes, and conventional gray matter volumetry may lack sensitivity to detect early structural changes. Here, we examined associations between insulin resistance and sulcal morphology, a measure that integrates cortical thinning, subcortical atrophy, and white matter degeneration into a single outcome, in 728 non-diabetic adults (518 men, 210 women; mean age 61.4 ± 11.6 years). Brain volumes were quantified using OpenMAP-T1, an automated deep learning-based parcellation tool, and associations between HOMA-IR and 30 cerebrospinal fluid-related regional volumes were examined using multiple linear regression adjusted for age, sex, and estimated total intracranial volume, with FDR correction for multiple comparisons. Higher HOMA-IR was significantly associated with greater frontal sulcal volumes (left: β = 596 mm³, right: β = 344 mm³; both FDR-corrected p < 0.001), with a dose-response relationship across insulin resistance categories. This association was observed only in men (sex × HOMA-IR interaction p = 0.019) and was strongest in participants younger than 70 years. Mediation analysis revealed that the relationship between BMI and frontal sulcal enlargement was largely accounted for by the indirect pathway through insulin resistance, with no significant direct effect of BMI. These findings suggest that sulcal morphology can detect metabolic effects on brain structure at a pre-diabetic stage, changes that were not apparent through frontal gray matter volumetry in the same sample, and identify insulin resistance as a potential modifiable target for preserving brain health.
SN - 2837-6056
ER -