Metabolic BMI phenotypes reveal sex-specific diabetes and heart risks in Chinese adults

Body mass index alone does a poor job of capturing the metabolic dangers that can hide behind a seemingly normal weight or an elevated one. A new analysis of four Chinese cohorts totalling 175,642 adults suggests a way forward: instead of relying on BMI alone, researchers clustered participants according to seven routine biomarkers, producing distinct BMI–biomarker phenotypic profiles that turned out to be linked to type 2 diabetes, chronic kidney disease and cardiovascular disease in strikingly sex-specific ways.

The clustering approach used residual-based grouping of the biomarkers, which allowed the team to identify metabolic patterns that BMI measurements on their own would miss. Two profiles showed consistent associations across both sexes: a high triglycerides profile was associated with increased type 2 diabetes risk, while a high blood pressure profile was associated with increased cardiovascular disease risk in both women and men.

The most notable differences emerged with a high fasting glucose profile. In women, this profile was associated with a sharply elevated risk of type 2 diabetes, with a hazard ratio of 2.38 (95% confidence interval 2.03–2.78). In men, the same profile was instead linked to cardiovascular disease, with a much more modest hazard ratio of 1.12 (95% CI 1.05–1.20). These are observational associations from cohort follow-up, not demonstrations of causation, but the divergence between the sexes suggests that the same biomarker signature may carry different clinical implications depending on sex.

The study also examined what happened when people’s phenotypes changed over time. During a median follow-up of 3.8 years, certain transitions between profiles were associated with lower subsequent cardiovascular risk in women. Reversion of the high fasting glucose profile was linked to a 68% lower risk of cardiovascular disease (HR 0.32, 95% CI 0.11–0.90), and reversion of the high blood pressure profile was linked to a 50% lower risk of stroke (HR 0.50, 95% CI 0.30–0.86). Because these transition analyses are observational, they cannot prove that reverting profiles directly reduces risk, and the wide confidence interval on the fasting glucose finding reflects considerable statistical uncertainty.

The authors frame the work as a phenotype-driven framework for characterizing metabolic heterogeneity and exploring how cardiometabolic risk changes over time. The article was published open access in Cardiovascular Diabetology on 29 October 2026 as peer-reviewed, accepted research shared ahead of the final version of record.

Subject of Research: BMI-discrepant biomarker phenotypes and their sex-specific associations with cardiometabolic risk in Chinese adults

Article Title: BMI-discrepant phenotypes and transitions reveal sex-specific heterogeneity and reshape cardiometabolic risk in Chinese adults

Article References: Lin, H., Wang, J., Yu, Y., Jia, X., Cao, Q., Qiao, H., Qin, G., Wu, S., Wang, S., Li, M., Xu, Y., Huang, F., Xu, X., Xu, Y., Xu, M., Wang, T., Tang, X., Ye, Z., Hu, R., … for the 4C Study Group (2026). BMI-discrepant phenotypes and transitions reveal sex-specific heterogeneity and reshape cardiometabolic risk in Chinese adults. Cardiovascular Diabetology. https://doi.org/10.1186/s12933-026-03425-4

Image Credits: AI Generated

DOI: 10.1186/s12933-026-03425-4

Keywords: BMI, biomarkers, type 2 diabetes, cardiovascular disease, chronic kidney disease, sex differences, metabolic heterogeneity, triglycerides, blood pressure, fasting glucose, Chinese cohorts, observational study