{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:34:04Z","timestamp":1786725244747,"version":"build-2736575974"},"reference-count":261,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Polish Society for Insulin Resistance Treatment"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Insulin resistance (IR) represents one of the most pressing problems in contemporary public health. Its estimated global prevalence ranges from approximately 15.5% to over 61%, depending on the population studied, the diagnostic criteria applied, and the method used for its assessment. Despite the scale of the problem, IR remains underrecognized and lacks formal definition as a distinct disease entity, even as a growing number of clinicians and researchers worldwide describe it as such. Its asymptomatic or mildly symptomatic course allows it to remain undetected for years, during which it makes a significant contribution to the development of type 2 diabetes, cardiovascular disease (CVD) and metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD), and has been increasingly linked to cellular senescence, certain cancers, neuropsychiatric disorders, and other metabolic conditions. The aim of this review was to summarize current knowledge on the pathophysiology, diagnosis, and clinical implications of insulin resistance, to discuss current challenges in its diagnosis, and to evaluate whether available scientific evidence supports its recognition as a distinct disease entity. This narrative review is based on clinical, epidemiological, and mechanistic data retrieved from PubMed and Google Scholar. Meta-analyses, systematic reviews, clinical and observational studies, clinical guidelines, and expert position statements were analyzed. Animal studies were excluded to maintain a focus on human public health implications. The diagnostic gold standard\u2014the hyperinsulinemic-euglycemic clamp\u2014was discussed, along with surrogate methods used in clinical practice (HOMA-IR, OGTT with insulin measurements, the TyG index, and the TG\/HDL-C ratio). Factors potentially contributing to the pathogenesis of IR were examined, including hyperinsulinemia (HI), high-carbohydrate diets, inflammation, stress, and sleep disturbances, as well as conditions in which IR occurs physiologically. The findings indicate that current evidence supports the need for a clearer clinical and diagnostic framework for insulin resistance and suggest that its recognition as a distinct disease entity could facilitate earlier diagnosis, improve the standardization of clinical management, and enable earlier metabolic intervention. Given the steadily rising prevalence of metabolic disease, systemic efforts directed at the early identification and treatment of IR may be a key component of strategies aimed at reducing the population-level burden of metabolic disease and its negative consequences.<\/jats:p>","DOI":"10.3390\/nu18162666","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:48:36Z","timestamp":1786722516000},"page":"2666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Insulin Resistance: Current State of Knowledge and Clinical Implications\u2014Toward a Better Diagnostic Framework and the Question of Its Disease Status"],"prefix":"10.3390","volume":"18","author":[{"given":"\u0141ukasz","family":"Rodze\u0144","sequence":"first","affiliation":[{"name":"Polish Society for Insulin Resistance Treatment (PTLI), 54-105 Wroc\u0142aw, Poland"},{"name":"Rodzen Brothers Foundation, 64-234 Wiele\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Rodze\u0144","sequence":"additional","affiliation":[{"name":"Polish Society for Insulin Resistance Treatment (PTLI), 54-105 Wroc\u0142aw, Poland"},{"name":"Rodzen Brothers Foundation, 64-234 Wiele\u0144, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4544-9624","authenticated-orcid":false,"given":"Damian","family":"Dy\u0144ka","sequence":"additional","affiliation":[{"name":"Polish Society for Insulin Resistance Treatment (PTLI), 54-105 Wroc\u0142aw, Poland"},{"name":"Institute of Health Sciences, Faculty of Medical and Health Sciences, University of Siedlce, 08-110 Siedlce, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"\u0141ojko","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Poznan University of Medical Science, 60-572 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5971-795X","authenticated-orcid":false,"given":"Hanna","family":"Karaku\u0142a-Juchnowicz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin, 20-439 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3244-7694","authenticated-orcid":false,"given":"Sebastian","family":"Kraszewski","sequence":"additional","affiliation":[{"name":"Polish Society for Insulin Resistance Treatment (PTLI), 54-105 Wroc\u0142aw, Poland"},{"name":"Department of Biomedical Engineering, Faculty of Fundamental Problems of Technology, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serafino","family":"Fazio","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9950-254X","authenticated-orcid":false,"given":"David","family":"Unwin","sequence":"additional","affiliation":[{"name":"Faculty of Health Social Care and Medicine, Edge Hill University, Ormskirk L39 4QP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bikman","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, 3052 LSB, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fahed, M., Abou Jaoudeh, M.G., Merhi, S., Mosleh, J.M.B., Ghadieh, R., Al Hayek, S., and El Hayek Fares, J.E. 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