Association of one-hour postload plasma glucose combined with metabolic dysfunction-associated steatotic liver disease and FIB-4 screening positivity with elevated LDL cholesterol and cerebrovascular stenosis.
Zuo F, Wang X, Xu C • Frontiers in endocrinology • 2026
In newly diagnosed T2DM, elevated 1h-PG was associated with MASLD/FIB-4 positivity; their combination was further linked to higher LDL-C and increased cerebrovascular stenosis risk, with LDL-C potentially acting as a partial mediator.
Key Findings
Results
MASLD was highly prevalent in newly diagnosed treatment-naïve T2DM patients, with nearly three-quarters of participants affected.
312 treatment-naïve adults with newly diagnosed T2DM were enrolled; 278 completed the standardized 75-g OGTT (age 24–78 years)
199 participants (71.6%) had ultrasound-confirmed MASLD
64 participants (23.0%) met the primary composite outcome of MASLD combined with age-specific FIB-4 screening positivity (age <65 years: FIB-4 ≥1.30; age ≥65 years: FIB-4 ≥2.00)
Study design was single-center, retrospective, and cross-sectional
Results
Participants meeting the MASLD/FIB-4 positivity primary outcome had significantly higher one-hour postload plasma glucose (1h-PG) than those who did not.
Mean 1h-PG was 17.7 ± 3.7 mmol/L in the MASLD/FIB-4 positive group versus 14.9 ± 3.8 mmol/L in those not meeting the primary outcome (P<0.001)
Each 1-mmol/L increment in 1h-PG was associated with an adjusted OR of 1.15 (95% CI 1.05–1.26; P=0.003) for meeting the primary outcome
This association persisted after multivariable adjustment
Results
Elevated LDL cholesterol and cerebrovascular stenosis were present in substantial minorities of the newly diagnosed T2DM cohort.
Elevated LDL-C (≥3.4 mmol/L) was present in 73 participants (26.3%)
Cerebrovascular stenosis (≥50% luminal narrowing in major intracranial or extracranial arteries) was present in 49 participants (17.6%)
Cerebrovascular stenosis was confirmed by ultrasound assessment of major intracranial and extracranial arteries
Results
The composite group of high 1h-PG combined with MASLD/FIB-4 positivity had the highest rate of cerebrovascular stenosis compared to the reference group.
The cerebrovascular stenosis rate was 34.8% in the high 1h-PG (≥Q3) plus MASLD/FIB-4 positive group versus 6.0% in the reference group
The adjusted OR for cerebrovascular stenosis in this composite group was 2.61 (95% CI 1.23–5.55; P=0.012)
High 1h-PG was defined as values at or above the third quartile (≥Q3)
Results
LDL-C appeared to partially mediate the association between the high 1h-PG/MASLD/FIB-4 composite and cerebrovascular stenosis.
Adding LDL-C to the model attenuated the adjusted OR for cerebrovascular stenosis from 3.42 to 2.61, representing approximately a 24% attenuation
This attenuation pattern was interpreted as indicating partial mediation by LDL-C
The association between the composite phenotype and cerebrovascular stenosis remained statistically significant after adjustment for LDL-C (OR 2.61, 95% CI 1.23–5.55; P=0.012)
Results
Adding MASLD/FIB-4 positivity and 1h-PG together into a combined model improved discriminative ability for cerebrovascular stenosis compared to 1h-PG alone.
AUC for 1h-PG alone was 0.661
AUC for the combined model (1h-PG plus MASLD/FIB-4 positivity) was 0.726
The improvement in AUC from 0.661 to 0.726 represents the incremental discriminative value of the combined approach
What This Means
This research suggests that in people newly diagnosed with type 2 diabetes, a blood sugar reading taken one hour after drinking a sugar solution (called one-hour postload plasma glucose, or 1h-PG) can help identify those who are more likely to have both fatty liver disease with signs of liver scarring and narrowing of blood vessels in the brain. The study followed 312 treatment-naïve adults and found that about 72% had fatty liver disease (MASLD), and nearly one in four also had elevated liver scarring markers (FIB-4 positive). Those with both fatty liver disease and elevated liver scarring markers had noticeably higher 1h-PG levels, and each 1 mmol/L increase in 1h-PG was linked to a 15% higher odds of having this combined liver condition.
The study also found that people who had both a high 1h-PG (in the top quarter of readings) and the combined fatty liver/scarring condition had about a 35% rate of significant cerebrovascular stenosis—narrowing of major brain-supplying blood vessels by 50% or more—compared to only 6% in those without these risk factors. Elevated LDL cholesterol ('bad' cholesterol) appeared to partly explain this link, as accounting for LDL-C reduced the strength of the association by about 24%, suggesting that fatty liver disease may raise cerebrovascular risk partly by worsening cholesterol metabolism. Combining 1h-PG with the liver disease markers improved the ability to identify patients at higher risk for cerebrovascular stenosis compared to using 1h-PG alone.
This research suggests that measuring blood sugar one hour after a glucose challenge—rather than relying only on standard fasting or two-hour readings—alongside liver health assessments, could help clinicians identify newly diagnosed type 2 diabetes patients at greater risk for both liver and vascular complications. However, the authors note that this was a single-center study with a relatively small sample size, and the findings need to be confirmed in larger, multicenter studies before broader clinical application.
Zuo F, Wang X, Xu C. (2026). Association of one-hour postload plasma glucose combined with metabolic dysfunction-associated steatotic liver disease and FIB-4 screening positivity with elevated LDL cholesterol and cerebrovascular stenosis.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1887611