The Progression of Cardiometabolic Disease: Validation of a New Cardiometabolic Disease Staging System Applicable to Obesity

OBJECTIVE: To validate a Cardiometabolic Disease Staging (CMDS) system for assigning risk level for diabetes, and all-cause and cardiovascular disease (CVD) mortality. DESIGN, AND METHODS: Two large national cohorts, CARDIA and NHANES III, were used to validate CMDS. CMDS: Stage 0: metabolically healthy; Stage 1: 1 or 2 Metabolic Syndrome risk factors (other than IFG); Stage 2: IFG or IGT or Metabolic Syndrome (without IFG); Stage 3: 2 of 3 (IFG, IGT, and/or Metabolic Syndrome); Stage 4: T2DM/CVD. RESULTS: In the CARDIA study, compared with Stage 0 metabolically healthy subjects, adjusted risk for diabetes exponentially increased from Stage 1 (HR 2.83, 95% CI 1.76–4.55), to Stage 2 (HR 8.06, 95% CI 4.91–13.2), to Stage 3 (HR 23.5, 95% CI 13.7–40.1) (p for trend <0.001). In NHANES III, both cumulative incidence and multivariable adjusted hazard ratios markedly increased for both all-cause and CVD mortality with advancement of the risk stage from Stage 0 to 4. Adjustment for BMI minimally affected the risks for diabetes and all-cause/CVD mortality using CMDS. CONCLUSION: CMDS can discriminate a wide range of risk for diabetes, CVD mortality, and all-cause mortality independent of BMI, and should be studied as a risk assessment tool to guide interventions that prevent and treat cardiometabolic disease.