BACKGROUND: The co-occurring epidemics of diabetes and obesity have increased the prevalence of Cardio-Kidney-Metabolic (CKM) syndrome. Comparative studies on long-term trends of its three core components [ischemic heart disease (IHD), diabetic kidney disease (DKD), non-alcoholic fatty liver disease (NAFLD)] across major countries are still limited. METHODS: We analyzed age-standardized disability-adjusted life year (DALY) rates of IHD, DKD, and NAFLD attributable to high fasting plasma glucose (HFPG) from 1990 to 2021 among seven representative middle-and high-income countries using Global Burden of Disease 2021 data. We assessed temporal trends, conducted hierarchical clustering, and projected burdens to 2050. RESULTS: We found substantial cross-country heterogeneity. From 1990 to 2021, IHD burden decreased significantly in the United States and Japan, while trends in China and India showed high uncertainty (coefficients of variation >100%) and should be interpreted with caution. DKD burden increased in Saudi Arabia and the United States but decreased in China. NAFLD burden increased in Saudi Arabia, the United States, India, and South Africa, while declining in China and Japan. Cluster analysis identified three patterns: "High IHD Burden" (India), "High Metabolic Burden" (Saudi Arabia), and "Low-Moderate Burden" (other countries). HFPG was associated with the largest share of DKD burden (Population Attributable Fraction [PAF] >80%) and a substantially smaller share of NAFLD burden (PAF <11%).Projections to 2050 show a sharp rise in DKD in the United States and India, together with increasing NAFLD burden, indicating a shift toward metabolic organ damage. CONCLUSIONS: The burden of CKM syndrome is substantial and dynamic, with marked cross-country differences. These findings support the need for integrated, multi-organ risk management strategies for metabolic disorders.