Metabolic Phenotyping of BMI to Characterize Cardiometabolic Risk: Evidence from Large Population-Based Cohorts

Abstract

Abstract Obesity is a risk factor for type 2 diabetes and cardiovascular disease. However, a substantial proportion of patients with these conditions have a seemingly normal body mass index (BMI). Conversely, not all obese individuals present with metabolic disorders giving rise to the concept of “metabolically healthy obese”. Using comprehensive lipidomic datasets from two large independent population cohorts in Australia (n = 14,831), we developed models that predicted BMI and calculated a metabolic BMI score (mBMI) as a measure of metabolic dysregulation associated with obesity. We postulated that the mBMI score would be an independent metric for defining obesity and help identify a hidden risk for metabolic disorders regardless of the measured BMI. Based on the difference between mBMI and BMI (mBMI delta; “mBMIΔ”), we identified individuals with a similar BMI but differing in their metabolic health profiles. Participants in the top quintile of mBMIΔ (Q5) were more than four times more likely to be newly diagnosed with T2DM (OR = 4.5; 95% CI = 3.1–6.6), more than two times more likely to develop T2DM over a five year follow up period (OR = 2.5; CI = 1.5–4.1) and had higher odds of cardiovascular disease (heart attack or stroke) (OR = 2.1; 95% CI = 1.5–3.1) relative to those in the bottom quintile (Q1). Exercise and diet were associated with mBMIΔ suggesting the ability to modify mBMI with lifestyle intervention. In conclusion, our findings show that, the mBMI score captures information on metabolic dysregulation that is independent of the measured BMI and so provides an opportunity to assess metabolic health to identify individuals at risk for targeted intervention and monitoring.