Adiposity-Metabolic Discordance Identifies Cardiometabolically Heterogeneous Profiles in Normal-Weight Adults: A...

Body mass index (BMI) is widely used to classify obesity and cardiometabolic risk, although it may fail to detect hidden metabolic impairment in individuals with normal body weight. Increasing evidence suggests that adiposity and metabolic dysfunction may not always coexist, giving rise to biologically discordant phenotypes associated with different cardiometabolic profiles.

This cross-sectional study was a secondary analysis of a subset of normal-weight adults selected from a larger database of Spanish workers undergoing routine occupational health examinations between 2019 and 2024. The final analytical sample included 166,008 workers aged 18-69 years with BMI values between 18.5 and 24.9 kg/m². Participants were classified into four adiposity-metabolic phenotypes according to the presence or absence of increased adiposity, operationally defined as a waist-to-height ratio (WtHR) ≥ 0.50, and metabolic dysfunction, defined as the presence of ≥2 of five adverse cardiometabolic criteria. METS-VF was additionally evaluated as a marker of visceral adiposity. Anthropometric, metabolic, vascular, and lifestyle-related variables were analyzed. Multivariable logistic regression models were used to evaluate factors associated with discordant phenotypes.

The concordant healthy phenotype was the most prevalent subgroup (78.9%), followed by adiposity-only (9.8%), metabolic-only (9.2%), and concordant high-risk phenotypes (2.0%). Despite normal BMI, approximately 21% of participants exhibited adiposity-metabolic discordance or combined high-risk status. The metabolic-only phenotype showed markedly adverse triglyceride, TG/HDL-c ratio, fasting glucose, and blood pressure values despite relatively preserved anthropometric parameters. Conversely, the adiposity-only phenotype exhibited increased central and visceral adiposity with comparatively preserved metabolic status. Sedentary lifestyle, unfavorable dietary adherence, smoking, older age, male sex, and higher BMI within the normal-weight range were independently associated with metabolically adverse phenotypes. The concordant high-risk phenotype demonstrated the greatest overall cardiometabolic burden.

Adults with normal BMI are metabolically heterogeneous and may present clinically relevant hidden-risk phenotypes despite conventional normal-weight classification. Adiposity-metabolic discordance highlights the limitations of BMI-based screening alone and supports the incorporation of multidimensional anthropometric, metabolic, and lifestyle-related assessment strategies for earlier identification of cardiometabolic risk.