Adiposity–metabolic discordance within normal BMI: sex-specific cardiometabolic phenotypes in 44,991 Spanish healthcare workers

Abstract

Background: Normal body mass index (BMI) does not necessarily indicate normal adiposity, and individuals with normal-weight obesity (NWO) may exhibit cardiometabolic abnormalities that remain undetected by BMI-based classification. We examined the cardiometabolic phenotype associated with NWO among adults with normal BMI, with particular attention to sex-related heterogeneity and the discriminatory ability of simple anthropometric measures. Methods: This cross-sectional study included 44,939 Spanish healthcare workers. NWO was defined as BMI 18.5–24.9 kg/m² combined with high or very high body-fat percentage according to sex- and age-specific classification. The primary analytical sample comprised 19,824 participants with normal BMI and either normal adiposity (n=19,040) or NWO (n=784). Cardiometabolic characteristics included glycaemic, lipid, blood-pressure, insulin-resistance-related, and metabolic-syndrome measures. Multivariable logistic regression was used to examine associations between NWO and cardiometabolic abnormalities, including NWO × sex interactions. Receiver operating characteristic analyses evaluated the ability of BMI, waist circumference, and waist-to-height ratio (WHtR) to discriminate NWO. Results: NWO was present in 3.10% (95% confidence interval [CI], 2.89–3.32%) of participants with normal BMI and was more prevalent in men than women (5.43% vs. 2.35%). Compared with normal adiposity, NWO was characterized by greater central adiposity, higher fasting glucose and insulin-resistance-related indices, lower HDL-C, and a more atherogenic lipid profile. At least one abnormal cardiometabolic domain was present in 53.1% of participants with NWO versus 29.2% with normal adiposity. After multivariable adjustment, NWO was associated with ≥1 abnormal domain (adjusted odds ratio [aOR] 2.24; 95% CI, 1.93–2.60), ≥2 abnormal domains (aOR 1.76; 95% CI, 1.36–2.29), elevated triglyceride-glucose index (aOR 3.28; 95% CI, 2.61–4.11), elevated low-density/high-density lipoprotein cholesterol ratio (aOR 3.45; 95% CI, 2.87–4.15), and elevated triglyceride/high-density lipoprotein cholesterol ratio (aOR 2.72; 95% CI, 2.18–3.38). Several associations differed by sex. In receiver operating characteristic (ROC) analyses, waist circumference showed the highest discrimination overall (area under the curve [AUC] 0.776; 95% CI, 0.756–0.795) and among men (AUC 0.836; 95% CI, 0.812–0.858), whereas BMI showed the highest discrimination among women (AUC 0.757; 95% CI, 0.733–0.780). Conclusions: Among Spanish healthcare workers with normal BMI, NWO identified a subgroup with greater concurrent cardiometabolic abnormality burden, particularly involving glycaemic, insulin-resistance-related, and atherogenic characteristics. Associations and anthropometric discrimination differed by sex, highlighting heterogeneity within the conventional normal-BMI category. Prospective studies are needed to determine the prognostic relevance of these phenotypes.