The progression of cardiometabolic disease: Validation of a new cardiometabolic disease staging system applicable to obesity


  • The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the National Center for Health Statistics, or the Centers for Disease Control and Prevention, or the National Heart, Lung, and Blood Institute.

  • Funding agencies: The Merit Review program of the Department of Veterans Affairs, National Institutes of Health (DK-038765 and DK-083562), and the UAB Diabetes Research Center (P60-DK079626).

  • Disclosure: Dr. Garvey is an advisor for Alkermes, Plc., Daiichi-Sankyo, Inc., LipoScience, VIVUS, Inc., Janssen Pharmaceuticals, and Tethys; is a speaker for Merck; and is a stockholder for Bristol-Myers Squibb Company, Isis/Genzyme, Merck, Pfizer, Inc., Eli Lilly and Company, and VIVUS, Inc. He has received research support from Amylin Pharmaceuticals, Inc., Merck & Co., and Weight Watchers International, Inc.

  • Author Contributions: Dr. Garvey and Dr. Guo conceived the study and analyzed data. Dr. Moellering reviewed and edited the manuscript. All authors were involved in writing the paper and had final approval of the submitted and published versions.



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: one or two metabolic syndrome risk factors [other than impaired fasting glucose (IFG)]; Stage 2: IFG or impaired glucose tolerance (IGT) or metabolic syndrome (without IFG); Stage 3: two of three (IFG, IGT, and/or metabolic syndrome); and Stage 4: type 2 diabetes mellitus/CVD.


In the CARDIA study, compared with Stage 0 metabolically healthy subjects, adjusted risk for diabetes exponentially increased from Stage 1 [hazard ratio (HR) 2.83, 95% confidence interval (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 HRs markedly increased for both all-cause and CVD mortality with advancement of the risk stage from Stages 0 to 4. Adjustment for body mass index (BMI) minimally affected the risks for diabetes and all-cause/CVD mortality using CMDS.


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.