{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:40:42Z","timestamp":1792100442069,"version":"4.4.0"},"reference-count":312,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Insulin resistance is a condition wherein cells fail to adequately respond to insulin. It is a prevalent medical condition associated with several diseases, such as type 2 diabetes mellitus, metabolic syndrome, hypertension, obesity, and polycystic ovary syndrome. Insulin resistance may be involved in metabolic disturbances, such as hyperglycemia, hyperinsulinemia, dyslipidemia, hyperuricemia, endothelial dysfunction, elevated inflammatory markers, and a prothrombotic state. Severe insulin resistance syndromes are a heterogeneous group of rare disorders. These disorders are characterized by profound insulin resistance, substantial metabolic abnormalities, and different clinical manifestations and complications. They may be hereditary or acquired, caused by defects in insulin action and cellular responsiveness to insulin. Severe insulin resistance syndromes may also be due to aberrations in adipose tissue function and development. The majority of these disorders are associated with an increased risk of severe complications and mortality. This review aims to summarize the current knowledge on the epidemiology, pathophysiology, complications and prognosis of severe insulin resistance syndromes, as well as to categorize these syndromes by disease process, including defects in insulin receptor, intracellular insulin signaling defects, lipodystrophies, etc.<\/jats:p>","DOI":"10.3390\/ijms26125669","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:51:24Z","timestamp":1749808284000},"page":"5669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Severe Insulin Resistance Syndromes: Clinical Spectrum and Management"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-8497","authenticated-orcid":false,"given":"Monika","family":"Pliszka","sequence":"first","affiliation":[{"name":"Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Cha\u0142ubi\u0144skiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leszek","family":"Szablewski","sequence":"additional","affiliation":[{"name":"Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Cha\u0142ubi\u0144skiego 5, 02-004 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0140-6736(01)36134-2","article-title":"Diabetes mellitus: A differentiation into insulin-sensitive and insulin-insensitive types","volume":"230","author":"Himsworth","year":"1936","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3390\/endocrines5020011","article-title":"Mechanism of insulin resistance in patients with obesity","volume":"5","author":"Arneth","year":"2024","journal-title":"Endocrines"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.2337\/dc22-2376","article-title":"Global prevalence of prediabetes","volume":"46","author":"Rooney","year":"2023","journal-title":"Diabetes Care"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zaman, G.S. 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