Front Endocrinol (Lausanne). 2026 Sep 16;17:1925899. doi: 10.3389/fendo.2026.1925899. eCollection 2026.
ABSTRACT
BACKGROUND AND AIMS: Whether metabolically unhealthy normal weight (MUNW) is associated with subclinical carotid atherosclerosis (SCAS) and how its risk compares with that of metabolically unhealthy overweight/obesity (MUO) remain uncertain, particularly in longitudinal analyses and across age groups.
METHODS: A cross-sectional sample (n = 26,202) and a longitudinal subcohort (n = 4,938) were derived from a health examination database; all participants in the longitudinal subcohort were free of SCAS at baseline. Participants were classified into four metabolic-obesity phenotypes based on body mass index and metabolic health status: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obesity (MUO). SCAS was defined as carotid intima-media thickness ≥1.0 mm and/or carotid plaque.
RESULTS: Compared with metabolically healthy normal weight (MHNW), MUNW was associated with increased odds of prevalent SCAS (OR 1.55, 95% CI 1.30-1.84) and increased risk of incident SCAS (HR 1.69, 95% CI 1.12-2.56). Compared with MUO, MUNW showed a numerically higher risk estimate for prevalent SCAS, although the difference was not statistically significant (OR 1.11, 95% CI 0.93-1.32, P = 0.247); a similar pattern was observed for incident SCAS (HR 1.25, 95% CI 0.83-1.91, P = 0.290). Metabolically healthy overweight/obesity (MHO) was associated with prevalent but not incident SCAS (OR 1.10, 95% CI 1.02-1.20; HR 1.14, 95% CI 0.94-1.38). A significant phenotype-by-age interaction was observed (P = 0.029); among adults aged <50 years, MUNW was associated with more than twofold higher odds of prevalent SCAS (OR 2.33, 95% CI 1.39-3.76). Findings were consistent in sensitivity analyses excluding covariates overlapping with phenotype definitions and in plaque-restricted analyses.
CONCLUSIONS: MUNW was associated with increased odds of prevalent SCAS and a higher hazard of incident SCAS after multivariable adjustment, with numerically higher risk estimates than MUO, although direct comparisons did not reach statistical significance.
PMID:42818702 | PMC:PMC13623737 | DOI:10.3389/fendo.2026.1925899