{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:06:06Z","timestamp":1784099166989,"version":"3.55.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 &amp;gt;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: \u201cHigh IHD Burden\u201d (India), \u201cHigh Metabolic Burden\u201d (Saudi Arabia), and \u201cLow-Moderate Burden\u201d (other countries). HFPG was associated with the largest share of DKD burden (Population Attributable Fraction [PAF] &amp;gt;80%) and a substantially smaller share of NAFLD burden (PAF &amp;lt;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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1858041","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:11:44Z","timestamp":1784095904000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["National divergence in cardio-kidney-metabolic syndrome burden and implications for health policy: a global burden of disease analysis with projections to 2050"],"prefix":"10.3389","volume":"14","author":[{"given":"Lizhi","family":"Li","sequence":"first","affiliation":[{"name":"Kidney Transplantation and Dialysis Center, The Second People's Hospital of Shanxi Province","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Kidney Transplantation and Dialysis Center, The Second People's Hospital of Shanxi Province","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Kidney Transplantation and Dialysis Center, The Second People's Hospital of Shanxi Province","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiang","family":"Jia","sequence":"additional","affiliation":[{"name":"Kidney Transplantation and Dialysis Center, The Second People's Hospital of Shanxi Province","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1606","DOI":"10.1161\/CIR.0000000000001184","article-title":"Cardiovascular-kidney-metabolic health: a presidential advisory from the American heart association","volume":"148","author":"Ndumele","year":"2023","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1136\/gutjnl-2023-330110","article-title":"Global prevalence of non-alcoholic fatty liver disease in type 2 diabetes mellitus: an updated systematic review and meta-analysis","volume":"72","author":"En Li Cho","year":"2023","journal-title":"Gut"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.3390\/jcm10092040","article-title":"Diabetic Kidney Disease, Cardiovascular disease and non-alcoholic fatty liver disease: a new triumvirate?","volume":"10","author":"Perdomo","year":"2021","journal-title":"J Clin Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3390\/biom15020213","article-title":"From Cardiovascular-kidney-metabolic syndrome to cardiovascular-renal-hepatic-metabolic syndrome: proposing an expanded framework","volume":"15","author":"Theodorakis","year":"2025","journal-title":"Biomolecules"},{"key":"B6","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s13098-025-01796-4","article-title":"(CArdio-Renal-DIAbetes-Liver-Metabolic Syndrome): a new proposition for an integrated multisystem metabolic disease.","volume":"17","author":"Godoy-Matos","year":"2025","journal-title":"Diabetol Metab Syndr"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S148","DOI":"10.1093\/geronb\/gbac032","article-title":"Cardiovascular Mortality Gap Between the United States and Other High Life Expectancy Countries in 2000-2016","volume":"77","author":"Acosta","year":"2022","journal-title":"J Gerontol B Psychol Sci Soc Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00757-8","article-title":"Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), healthy life expectancy (HALE) for 371 diseases, injuries in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021","year":"2024","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00367-2","article-title":"Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021","year":"2024","journal-title":"Lancet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"155999","DOI":"10.1016\/j.metabol.2024.155999","article-title":"Global burden of metabolic diseases, 1990-2021","volume":"160","author":"Zhang","year":"2024","journal-title":"Metabolixsm"},{"key":"B12","doi-asserted-by":"publisher","first-page":"155402","DOI":"10.1016\/j.metabol.2023.155402","article-title":"The global syndemic of metabolic diseases in the young adult population: a consortium of trends and projections from the Global Burden of Disease 2000-2019","volume":"141","author":"Chong","year":"2023","journal-title":"Metabolism"},{"key":"B13","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12902-018-0244-4","article-title":"Prevalence of metabolic syndrome in Saudi Arabia - a cross sectional study","volume":"18","author":"Al-Rubeaan","year":"2018","journal-title":"BMC Endocr Disord"},{"key":"B14","doi-asserted-by":"publisher","first-page":"973","DOI":"10.15537\/smj.2023.44.10.20230450","article-title":"Understanding the prevalence, progression, and management of metabolic syndrome in Saudi Arabia","volume":"44","author":"Alshehri","year":"2023","journal-title":"Saudi Med J"},{"key":"B15","doi-asserted-by":"publisher","first-page":"100156","DOI":"10.1016\/j.lansea.2023.100156","article-title":"The burgeoning cardiovascular disease epidemic in Indians - perspectives on contextual factors and potential solutions","volume":"12","author":"Kalra","year":"2023","journal-title":"Lancet Reg Health Southeast Asia"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e038644","DOI":"10.1161\/JAHA.124.038644","article-title":"Heart Disease Mortality in the United States, 1970 to 2022","volume":"14","author":"King","year":"2025","journal-title":"J Am Heart Assoc"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2561","DOI":"10.1111\/dom.16256","article-title":"Global, regional and national burden of ischaemic heart disease attributable to high body mass index and low physical activity from 1990 to 2021","volume":"27","author":"Lin","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e032626","DOI":"10.1161\/JAHA.123.032626","article-title":"Diabetes-Related Macrovascular Complications Are Associated With an Increased Risk of Diabetic Microvascular Complications: A Prospective Study of 1518 Patients With Type 1 Diabetes and 20 802 Patients With Type 2 Diabetes in the UK Biobank","volume":"13","author":"Zhang","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"B19","doi-asserted-by":"publisher","first-page":"330","DOI":"10.3390\/ijms26073330","article-title":"Comprehending the role of metabolic and hemodynamic factors alongside different signaling pathways in the pathogenesis of diabetic nephropathy","volume":"26","author":"Ratan","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1631053","DOI":"10.3389\/fmed.2025.1631053","article-title":"Diabetic kidney disease: from pathogenesis to multimodal therapy-current evidence and future directions","volume":"12","author":"Zhang","year":"2025","journal-title":"Front Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"7349","DOI":"10.3390\/jcm12237349","article-title":"Pathomechanisms of Diabetic Kidney Disease","volume":"12","author":"Sinha","year":"2023","journal-title":"J Clin Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1186\/s12933-024-02371-3","article-title":"Sex-difference of multifactorial intervention on cardiovascular and mortality risk in DKD: post-hoc analysis of a randomised clinical trial","volume":"23","author":"Minutolo","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s12933-021-01343-1","article-title":"Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease","volume":"20","author":"Sasso","year":"2021","journal-title":"Cardiovasc Diabetol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"B25","doi-asserted-by":"publisher","first-page":"101133","DOI":"10.1016\/j.aohep.2023.101133","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"29","author":"Rinella","year":"2024","journal-title":"Ann Hepatol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"154770","DOI":"10.1016\/j.metabol.2021.154770","article-title":"Non-alcoholic fatty liver disease, insulin resistance, metabolic syndrome and their association with vascular risk","volume":"119","author":"Muzurovi\u0107","year":"2021","journal-title":"Metabolism"},{"key":"B27","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1038\/s41392-023-01333-7","article-title":"Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B28","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/S2213-8587(22)00003-1","article-title":"A global view of the interplay between non-alcoholic fatty liver disease and diabetes","volume":"10","author":"Stefan","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1016\/j.eprac.2022.03.010","article-title":"American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD)","volume":"28","author":"Cusi","year":"2022","journal-title":"Endocr Pract"},{"key":"B30","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3390\/biomedicines13010135","article-title":"Integrated Management of Cardiovascular-Renal-Hepatic-Metabolic Syndrome: Expanding Roles of SGLT2is, GLP-1RAs, and GIP\/GLP-1RAs","volume":"13","author":"Theodorakis","year":"2025","journal-title":"Biomedicines"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.3390\/pharmaceutics15071995","article-title":"SGLT2 Inhibitors in the Treatment of Diabetic Kidney Disease: More than Just Glucose Regulation","volume":"15","author":"Klen","year":"2023","journal-title":"Pharmaceutics"},{"key":"B32","doi-asserted-by":"publisher","first-page":"3668","DOI":"10.3390\/ijms23073668","article-title":"SGLT2 Inhibitors as the Most Promising Influencers on the Outcome of Non-Alcoholic Fatty Liver Disease","volume":"23","author":"Mirarchi","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1210\/clinem\/dgab578","article-title":"The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD","volume":"107","author":"Patel Chavez","year":"2022","journal-title":"J Clin Endocrinol Metab"},{"key":"B34","doi-asserted-by":"publisher","first-page":"103170","DOI":"10.1016\/j.cpcardiol.2025.103170","article-title":"The triadic relationship between nonalcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease: From molecular mechanisms to clinical management","volume":"50","author":"Jin","year":"2025","journal-title":"Curr Probl Cardiol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1007\/s00125-022-05787-2","article-title":"Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"65","author":"Davies","year":"2022","journal-title":"Diabetologia"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2899","DOI":"10.1097\/CM9.0000000000002927","article-title":"Summary of the 2022 Report on Cardiovascular Health and Diseases in China","volume":"136","author":"Wang","year":"2023","journal-title":"Chin Med J"}],"container-title":["Frontiers in Public Health"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2026.1858041\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:11:45Z","timestamp":1784095905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpubh.2026.1858041\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":36,"alternative-id":["10.3389\/fpubh.2026.1858041"],"URL":"https:\/\/doi.org\/10.3389\/fpubh.2026.1858041","relation":{},"ISSN":["2296-2565"],"issn-type":[{"value":"2296-2565","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]},"article-number":"1858041"}}