Risk factors for cardiovascular disease, chronic kidney disease, and type 2 diabetes in populations with overweight and obesity: an umbrella review and cohort analysis

AIMS: Individuals with overweight and obesity are at high risk of cardiovascular disease (CVD), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM). We aimed to identify the risk factors for CVD, CKD, and T2DM among individuals with overweight and obesity, and to validate the associations of these risk factors with the three outcomes. METHODS: We conducted an umbrella review and a cohort analysis. Seven databases were searched from inception to December 31, 2025. Systematic reviews reporting the risk factors in populations with overweight and obesity, and CVD, CKD, or T2DM were included. The ROBIS and GRADE tools were used to assess the methodological quality and certainty of evidence. A cohort study dataset from the China Health and Retirement Longitudinal Study (CHARLS) was used for validation. Associations with the composite outcome and its individual components (CVD, CKD, and T2DM) were examined. RESULTS: Nine systematic reviews were included in the umbrella review, and three key factors were identified. Anthropometric measures were associated with CVD (HRs 1.10-1.29) and T2DM (RRs 1.31-1.88). Compared with metabolically healthy individuals, those with metabolically unhealthy phenotypes had HRs ranging from 1.46 to 2.68. Metabolically unhealthy individuals had higher risks (RRs 2.42-5.90). Unhealthy dietary patterns increased CVD, CKD and T2DM risk (HRs 1.11-2.05), whereas healthy dietary patterns reduced risk. In this cohort study, 1,305 participants were included, and 538 developed CVD, CKD or T2DM. Transitioning from a metabolically healthy to a metabolically unhealthy phenotype (OR 1.66 [1.19, 2.30]), transitioning from a metabolically unhealthy to a metabolically healthy phenotype (OR 1.56 [1.08, 2.24]), and maintaining a stable metabolically unhealthy status (OR 1.88 [1.39, 2.54]) were significantly associated with an increased risk of incident CVD, CKD and T2DM composite; disease-specific analyses indicated that this association was driven primarily by T2DM. CONCLUSIONS: Our analyses revealed that anthropometric measures, metabolic phenotypes, and dietary patterns are associated with CVD, CKD, and T2DM among individuals with overweight and obesity, especially T2DM. Integrated prevention strategies targeting these modifiable risk factors should be prioritized to optimize clinical management. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420261350841.