Plasma FGF21 levels were significantly associated with intracranial atherosclerotic stenosis in patients with type 2 diabetes mellitus, with higher FGF21 levels predicting moderate to severe stenosis.
Key Findings
Results
Plasma FGF21 levels differed significantly across intracranial atherosclerotic stenosis severity groups in patients with type 2 diabetes.
110 patients with type 2 diabetes were recruited and categorized into three groups: no stenosis (0%), mild stenosis (1-49%), and moderate to severe stenosis (≥50%)
Median FGF21 levels were 114.35 (IQR 105.35-124.04) ng/L in the no stenosis group, 124.81 (IQR 118.84-134.47) ng/L in the mild stenosis group, and 132.18 (IQR 120.43-150.05) ng/L in the moderate to severe stenosis group
The difference across groups was statistically significant (H = 17.327, p < 0.001)
Stenosis severity was evaluated using the internationally recognized modified Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) criteria
Results
FGF21 levels were significantly higher in the moderate-to-severe stenosis group compared to those with no or mild stenosis combined.
Moderate-to-severe stenosis group median FGF21: 132.18 (IQR 120.43-150.05) ng/L
No stenosis + mild stenosis combined group median FGF21: 122.44 (IQR 109.88-129.19) ng/L
The difference was statistically significant (U = -3.138, p = 0.002)
Results
The highest tertile of FGF21 level was independently associated with moderate to severe intracranial atherosclerotic stenosis after covariate adjustment.
The highest tertile (T3) of FGF21 (>129.55 ng/L) was associated with moderate to severe stenosis after adjusting for age and α-glucosidase inhibitor use (OR = 6.453, 95% CI: 1.944-21.415, p = 0.002)
Log-transformed FGF21 (lnFGF21) was also independently associated with moderate to severe stenosis (OR = 2.191, 95% CI: 1.277-3.759, p = 0.004)
Covariates adjusted for included age and α-glucosidase inhibitor use
Results
A combination of lnFGF21, age, and α-glucosidase inhibitor use predicted moderate to severe intracranial atherosclerotic stenosis with moderate discriminative ability.
The combined model yielded an AUC of 0.768 (95% CI: 0.670-0.865) on ROC curve analysis
Internal validation was performed using bootstrap resampling with 1,000 replicates
Model calibration metrics from bootstrap validation: MAE = 0.021, MSE = 0.00064, 90th percentile of absolute error = 0.038, indicating good model stability
Results
This study identified a significant cross-sectional association between plasma FGF21 levels and intracranial atherosclerotic stenosis in patients with type 2 diabetes mellitus.
This is described as the first study to explore the relationship between FGF21 and intracranial atherosclerotic stenosis
FGF21 levels were measured using enzyme-linked immunosorbent assays (ELISA)
The study design was cross-sectional, limiting causal inference
Prior literature had established associations between FGF21 and atherosclerosis and coronary artery disease severity, but not intracranial disease
What This Means
This research suggests that a hormone called FGF21 (fibroblast growth factor 21), measured in the blood, is linked to the narrowing of blood vessels inside the brain (intracranial atherosclerotic stenosis) in people with type 2 diabetes. The study enrolled 110 diabetic patients and found that those with more severe narrowing of their brain arteries had higher levels of FGF21 in their blood. Specifically, patients with moderate to severe stenosis had notably higher FGF21 levels than those with no or mild stenosis.
The researchers also found that people in the highest third of FGF21 levels had more than six times the odds of having moderate to severe brain artery narrowing compared to those in the lowest two-thirds, even after accounting for age and certain diabetes medications. When FGF21 was combined with age and medication use in a predictive model, it could identify patients with significant brain artery narrowing with reasonable accuracy (AUC of 0.768).
This research matters because intracranial atherosclerotic stenosis is a major cause of stroke, and people with type 2 diabetes are at elevated risk. While prior studies had linked FGF21 to heart artery disease, this is the first to connect it to brain artery narrowing. These findings raise the possibility that FGF21 could serve as a blood-based marker to help identify diabetic patients at higher risk for brain vessel disease, though further prospective and experimental studies are needed to confirm causality and understand the underlying mechanisms.
Wang Q, Zhang X, Xiao Y, Zhou S, Liu Y, Xie C, et al.. (2026). Plasma FGF21 is associated with intracranial atherosclerotic stenosis in patients with type 2 diabetes mellitus.. Frontiers in neurology. https://doi.org/10.3389/fneur.2026.1904036