Metabolic syndrome
Abstract
The metabolic syndrome (MetS) is a multiplex modifiable risk factor for cardiovascular disease, type 2 diabetes mellitus and other health outcomes, and is a major challenge to clinical practice and public health. The rising global prevalence of MetS, driven by urbanization, sedentary lifestyles and dietary changes, underlines the urgency of addressing this syndrome. We explore the complex underlying mechanisms, including genetic predisposition, insulin resistance, accumulation of dysfunctional adipose tissue and ectopic lipids in abdominal obesity, systemic inflammation and dyslipidaemia, and how they contribute to the clinical manifestations of MetS. Diagnostic approaches vary but commonly focus on abdominal obesity (assessed using waist circumference), hyperglycaemia, dyslipidaemia and hypertension, highlighting the need for population-specific and phenotype-specific diagnostic strategies. Management of MetS prioritizes lifestyle modifications, such as healthy dietary patterns, physical activity and management of excess visceral and ectopic adiposity, as foundational interventions. We also discuss emerging therapies, including new pharmacological treatments and surgical options, providing a forward-looking perspective on MetS research and care. This Primer aims to inform clinicians, researchers and policymakers about MetS complexities, advocating for a cohesive, patient-centred management and prevention strategy. Emphasizing the multifactorial nature of MetS, this Primer ca…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Central obesity measures-particularly BRI-are indispensable for accurate risk classification.
“illustrating the indispensable value of central obesity measures—particularly BRI—in accurate risk classification [35–37].”
From Machine learning with the body roundness index and associated indicators: a new approach to predicting metabolic syndrome (2025) · cites this paper as [36]
Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011 · see citing works
Dapagliflozin in Patients with Chronic Kidney Disease
Heerspink, H. J. L., Stefánsson, B. V., Correa-Rotter, R., Chertow, G. M., Greene, T., Hou, F.-F., Mann, J. F. E., McMurray, J. J. V., Lindberg, M., Rossing, P., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2024816 · Cited by 5,618 · see citing works
The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy
Lewis, E. J., Hunsicker, L. G., Bain, R. P., & Rohde, R. D. (1993) · New England Journal of Medicine · doi:10.1056/nejm199311113292004 · Cited by 5,394 · see citing works
Tirzepatide Once Weekly for the Treatment of Obesity
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2206038 · Cited by 3,838 · see citing works
Effect of a multifactorial intervention on mortality in type 2 diabetes
Gæde, P., Lund-Andersen, H., Parving, H.-H., & Pedersen, O. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0706245 · Cited by 3,489 · see citing works
Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., Granowitz, C., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812792 · Cited by 3,317 · see citing works
Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes
Bakris, G. L., Agarwal, R., Anker, S. D., Pitt, B., Ruilope, L. M., Rossing, P., Kolkhof, P., Nowack, C., Schloemer, P., Joseph, A., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2025845 · Cited by 2,935 · see citing works
Empagliflozin in Patients with Chronic Kidney Disease
The EMPA-KIDNEY Collaborative Group (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2204233 · Cited by 2,754 · see citing works
2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults
Jensen, M. D., Ryan, D. H., Apovian, C. M., Ard, J. D., Comuzzie, A. G., Donato, K. A., Hu, F. B., Hubbard, V. S., Jakicic, J. M., Kushner, R. F., et al. (2014) · Circulation · doi:10.1161/01.cir.0000437739.71477.ee · Cited by 2,735 · see citing works
Dynamics of fat cell turnover in humans
Spalding, K. L., Arner, E., Westermark, P. O., Bernard, S., Buchholz, B. A., Bergmann, O., Blomqvist, L., Hoffstedt, J., Näslund, E., Britton, T., et al. (2008) · Nature · doi:10.1038/nature06902 · Cited by 2,357 · see citing works
Cardiovascular-kidney-metabolic health: a presidential advisory from the American Heart Association
Ndumele, C. E., Rangaswami, J., Chow, S. L., Neeland, I. J., Tuttle, K. R., Khan, S. S., Coresh, J., Mathew, R. O., Baker-Smith, C. M., Carnethon, M. R., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001184 · Cited by 2,208 · see citing works
Self-citationCornier, M.-A., Dabelea, D., Hernandez, T. L., Lindstrom, R. C., Steig, A. J., Stob, N. R., Van Pelt, R. E., Wang, H., & Eckel, R. H. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0024 · Cited by 2,162 · see citing works
Metabolic Syndrome and Risk of Incident Cardiovascular Events and Death
Gami, A. S., Witt, B. J., Howard, D. E., Erwin, P. J., Gami, L. A., Somers, V. K., & Montori, V. M. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.09.032 · Cited by 1,888 · see citing works
Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.
Perkovic, V., Tuttle, K. R., Rossing, P., Mahaffey, K. W., Mann, J. F. E., Bakris, G., Baeres, F. M. M., Idorn, T., Bosch-Traberg, H., Lausvig, N. L., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2403347 · Cited by 1,849 · see citing works
Comment on the provisional report from the WHO consultation
(1999) · Diabetic Medicine · doi:10.1046/j.1464-5491.1999.00059.x · Cited by 1,820 · see citing works
New Criteria for `Obesity Disease' in Japan
The Examination Committee of Criter (2002) · Circulation Journal · doi:10.1253/circj.66.987 · Cited by 1,650 · see citing works
Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk
Després, J.-P., Lemieux, I., Bergeron, J., Pibarot, P., Mathieu, P., Larose, E., Rodés-Cabau, J., Bertrand, O. F., & Poirier, P. (2008) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.107.159228 · Cited by 1,589 · see citing works
The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux
Samuel, V. T., & Shulman, G. I. (2016) · Journal of Clinical Investigation · doi:10.1172/jci77812 · Cited by 1,484 · see citing works
Alexander, C. M., Landsman, P. B., Teutsch, S. M., & Haffner, S. M. (2003) · Diabetes · doi:10.2337/diabetes.52.5.1210 · Cited by 1,475 · cited 1× · see citing works
“…as inflammation, endothelial dysfunction, a prothrombotic state and an excess of circulating small, dense LDL particles as well as abdominal obesity and hepatic steatosis, are not routinely measured in clinical practice, nor are they directly targeted by existing pharmacological therapies 152 .”
Effects of aspirin for primary prevention in persons with diabetes mellitus
The ASCEND Study Collaborative Group (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1804988 · Cited by 1,189 · see citing works
Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
Jastreboff, A. M., Kaplan, L. M., Frías, J. P., Wu, Q., Du, Y., Gurbuz, S., Coskun, T., Haupt, A., Milicevic, Z., & Hartman, M. L. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2301972 · Cited by 1,174 · see citing works
Picot, J., Jones, J., Colquitt, J., Gospodarevskaya, E., Loveman, E., Baxter, L., & Clegg, A. (2009) · Health Technology Assessment · doi:10.3310/hta13410 · Cited by 1,066 · cited 1× · see citing works
“of low-risk procedures such as cholecystectomy, hysterectomy and appendectomy 159,160 .”
Baigent, C., Emberson, J., Haynes, R., Herrington, W. G., Judge, P., Landray, M. J., Mayne, K. J., Ng, S. Y. A., Preiss, D., Roddick, A. J., et al. (2022) · The Lancet · doi:10.1016/s0140-6736(22)02074-8 · Cited by 1,020 · see citing works
Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome — An allostatic perspective
Virtue, S., & Vidal-Puig, A. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.12.006 · Cited by 1,013 · see citing works
Why does obesity cause diabetes?
Klein, S., Gastaldelli, A., Yki-Järvinen, H., & Scherer, P. E. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.012 · Cited by 939 · see citing works
Self-citationKhan, S. S., Coresh, J., Pencina, M. J., Ndumele, C. E., Rangaswami, J., Chow, S. L., Palaniappan, L. P., Sperling, L. S., Virani, S. S., Ho, J. E., et al. (2023) · Circulation · doi:10.1161/cir.0000000000001191 · Cited by 797 · see citing works
Self-citationOverproduction of large VLDL particles is driven by increased liver fat content in man
Adiels, M., Taskinen, M.-R., Packard, C., Caslake, M. J., Soro-Paavonen, A., Westerbacka, J., Vehkavaara, S., Häkkinen, A., Olofsson, S.-O., Yki-Järvinen, H., et al. (2006) · Diabetologia · doi:10.1007/s00125-005-0125-z · Cited by 690 · see citing works
Mantovani, A., Csermely, A., Petracca, G., Beatrice, G., Corey, K. E., Simon, T. G., Byrne, C. D., & Targher, G. (2021) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(21)00308-3 · Cited by 674 · see citing works
Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology
Arner, E., Westermark, P. O., Spalding, K. L., Britton, T., Rydén, M., Frisén, J., Bernard, S., & Arner, P. (2010) · Diabetes · doi:10.2337/db09-0942 · Cited by 645 · see citing works
Gastaldelli, A., Cusi, K., Pettiti, M., Hardies, J., Miyazaki, Y., Berria, R., Buzzigoli, E., Sironi, A. M., Cersosimo, E., Ferrannini, E., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.04.068 · Cited by 629 · see citing works
Components of a Cardioprotective Diet: New Insights
Mozaffarian, D., Appel, L. J., & Van Horn, L. (2011) · Circulation · doi:10.1161/circulationaha.110.968735 · Cited by 571 · see citing works
Impaired adipogenesis and dysfunctional adipose tissue in human hypertrophic obesity
Hammarstedt, A., Gogg, S., Hedjazifar, S., Nerstedt, A., & Smith, U. (2018) · Physiological Reviews · doi:10.1152/physrev.00034.2017 · Cited by 462 · see citing works
From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options
Gastaldelli, A., & Cusi, K. (2019) · JHEP Reports · doi:10.1016/j.jhepr.2019.07.002 · Cited by 455 · see citing works
Self-citationDose-Response Effect of Elevated Plasma Free Fatty Acid on Insulin Signaling
Belfort, R., Mandarino, L., Kashyap, S., Wirfel, K., Pratipanawatr, T., Berria, R., DeFronzo, R. A., & Cusi, K. (2005) · Diabetes · doi:10.2337/diabetes.54.6.1640 · Cited by 404 · see citing works
Plasma fetuin-A levels and the risk of type 2 diabetes
Stefan, N., Fritsche, A., Weikert, C., Boeing, H., Joost, H.-G., Häring, H.-U., & Schulze, M. B. (2008) · Diabetes · doi:10.2337/db08-0538 · Cited by 379 · see citing works
Management of common clinical problems experienced by survivors of cancer
Emery, J., Butow, P., Lai-Kwon, J., Nekhlyudov, L., Rynderman, M., & Jefford, M. (2022) · The Lancet · doi:10.1016/s0140-6736(22)00242-2 · Cited by 326 · see citing works
The CardioMetabolic Health Alliance
Sperling, L. S., Mechanick, J. I., Neeland, I. J., Herrick, C. J., Després, J.-P., Ndumele, C. E., Vijayaraghavan, K., Handelsman, Y., Puckrein, G. A., Araneta, M. R. G., et al. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.06.1328 · Cited by 294 · see citing works
Self-citationIncreased lipid availability impairs insulin-stimulated ATP synthesis in human skeletal muscle
Brehm, A., Krssak, M., Schmid, A. I., Nowotny, P., Waldhäusl, W., & Roden, M. (2006) · Diabetes · doi:10.2337/diabetes.55.01.06.db05-1286 · Cited by 239 · see citing works
Ntuk, U. E., Gill, J. M. R., Mackay, D. F., Sattar, N., & Pell, J. P. (2014) · Diabetes Care · doi:10.2337/dc13-2966 · Cited by 220 · see citing works
Wewege, M. A., Thom, J. M., Rye, K.-A., & Parmenter, B. J. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.05.002 · Cited by 210 · see citing works
Campbell, J. E., Müller, T. D., Finan, B., DiMarchi, R. D., Tschöp, M. H., & D’Alessio, D. A. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.07.010 · Cited by 149 · see citing works
Lancet Diabetes & Endocrinology Commission on the Definition and Diagnosis of Clinical Obesity
Rubino, F., Batterham, R. L., Koch, M., Mingrone, G., le Roux, C. W., Farooqi, I. S., Farpour-Lambert, N., Gregg, E. W., & Cummings, D. E. (2023) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(23)00058-x · Cited by 126 · see citing works
Saponaro, C., Sabatini, S., Gaggini, M., Carli, F., Rosso, C., Positano, V., Armandi, A., Caviglia, G. P., Faletti, R., Bugianesi, E., et al. (2022) · Liver International · doi:10.1111/liv.15377 · Cited by 116 · see citing works
Self-citationManagement of Obesity in Cardiovascular Practice
Després, J.-P., Carpentier, A. C., Tchernof, A., Neeland, I. J., & Poirier, P. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.05.035 · Cited by 87 · see citing works
Self-citationModification of lipoprotein metabolism and function driving atherogenesis in diabetes
Luciani, L., Pedrelli, M., & Parini, P. (2024) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2024.117545 · Cited by 72 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Novel GLP-1-based Medications for Type 2 Diabetes and Obesity
Son, J. W., le Roux, C. W., Blüher, M., Nauck, M. A., & Lim, S. (2026) · Endocrine Reviews · doi:10.1210/endrev/bnaf036 · Cited by 33 · see citing works
Self-citationHe, Y., Chen, Z., Tang, Z., Qin, Y., & Wang, F. (2025) · BMC Public Health · doi:10.1186/s12889-025-23858-y · Cited by 5 · see citing works
García-Niño, W. R., Zúñiga-Muñoz, A. M., & Maldonado-Macías, X. P. (2026) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2026.178715 · Cited by 1 · see citing works
- Authors
- Neeland, I. J., Lim, S., Tchernof, A., Gastaldelli, A., Rangaswami, J., Ndumele, C. E., Powell-Wiley, T. M., & Després, J.-P.
- Affiliations
- University Hospitals of Cleveland (US)
- Seoul National University (KR)
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- Istituto di Fisiologia Clinica (IT)
- George Washington University (US)
- Johns Hopkins University (US)
- Corresponding author
- Lim, Soo
- Després, Jean-Pierre
- ORCID
- Venue
- Nature Reviews Disease Primers
- Published
- 2024-10-17
- Volume
- 10
- Issue
- 1
- Pages
- 77-77
- ISSN
- 2056-676X (ISSN-L)
- OpenAlex
- W4403496222
- Cited by
- 463
- References
- 45
- Citations by year
- 2026: 250 · 2025: 202 · 2024: 10 · 2021: 1
- FWCI
- 27.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Disease Primers (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- metabolic syndrome, cardiovascular risk, type 2 diabetes, abdominal obesity, insulin resistance, dyslipidemia, hypertension, hyperglycemia, visceral adipose tissue, systemic inflammation, genetic susceptibility, metabolic syndrome diagnostic criteria, lifestyle modification, pharmacotherapy, bariatric surgery, sedentary lifestyle, urbanization
- MeSH terms
- Diabetes Mellitus, Type 2, Humans, Insulin Resistance, Life Style, Risk Factors, Metabolic Syndrome, Obesity, Abdominal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
