Sex-Specific Cardiometabolic Phenotypes of Metabolic Syndrome Identified by Latent Class Analysis in Indian Adults

Metabolic syndrome (MetS) encompasses a constellation of cardiometabolic risk factors, yet its phenotypic diversity remains underexplored.

The study aimed to identify sex-specific latent phenotypes of MetS using key clinical indicators and to evaluate their association with metabolic risk.

We conducted a latent class analysis among 440 adults aged 20-55 years using five indicators - waist circumference, systolic and diastolic blood pressure (BP), high-density lipoprotein (HDL) cholesterol, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Sex-specific models and sensitivity analyses were used to assess measurement invariance and model robustness.

A three-class model demonstrated optimal fit (lowest Bayesian Information Criterion, entropy ≥0.99). Class 1 (43%) was predominantly low-risk, with minimal abdominal obesity and no hypertension. Class 2 (23%) represented a hypertensive-adiposity phenotype, characterized by universal elevated waist circumference and systolic hypertension but moderate insulin resistance. Class 3 (35%) was marked by pronounced insulin resistance and dyslipidemia, with high HOMA-IR and triglycerides (TG) despite minimal hypertension. Sex-stratified models fit significantly better than pooled models (G ² = 130.4, P < 0.001), revealing differential indicator profiles - men showed higher low-HDL prevalence, whereas women exhibited greater diastolic load. Sensitivity analysis collapsing BP indicators confirmed class stability and preserved metabolic gradients. Bolck-Croon-Hagenaars - weighted analysis revealed a stepwise increase in fasting blood sugar and TG across classes.

Our findings highlight three robust cardiometabolic phenotypes with distinct sex-specific profiles. The hypertensive-adiposity and insulin-resistant classes suggest divergent risk pathways requiring tailored interventions. Even the low-risk group exhibited intermediate lipid elevation, supporting the need for universal lifestyle counseling alongside precision screening strategies.