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From the Reaven\u2019s insulin resistance syndrome to the DeFronzo\u2019s triumvirate (skeletal muscle, liver and beta-cell) and to Kahn\u2019s discovery (among many others) of insulin receptor downregulation and autophosphorylation, an enthusiastic age of metabolic in vivo and in vitro research took place, making the promise of a resolutory ending. However, from many published data (those of insulin receptoropathies and lipodystrophies, the genome-wide association studies results, the data on reversibility of type 2 diabetes after bariatric surgery or very-low-calorie diets, and many others) it appears that insulin resistance is not a primary defect but it develops secondarily to increased fat mass. In particular, it develops from a mismatch between the surplus caloric intake and the storage capacity of adipose tissue. On this basis, we propose to change the today\u2019s definition of type 2 diabetes in adiposity-based diabetes.<\/jats:p><jats:p><jats:bold><jats:italic>Level of Evidence<\/jats:italic><\/jats:bold> as a narrative review a vast array of studies have been included in the analysis, ranging from properly designed randomized controlled trials to case studies; however, the overall conclusion may be regarded as level IV.<\/jats:p>","DOI":"10.1007\/s40519-021-01109-4","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T07:53:17Z","timestamp":1612857197000},"page":"2429-2441","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Is type 2 diabetes an adiposity-based metabolic disease? From the origin of insulin resistance to the concept of dysfunctional adipose tissue"],"prefix":"10.1007","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9634-1501","authenticated-orcid":false,"given":"Paolo","family":"Sbraccia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"D\u2019Adamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Guglielmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"1109_CR1","doi-asserted-by":"crossref","unstructured":"Insulin Resistance and Sensitivity\u00a0(1940) Br Med J 1(4139):734. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2177405\/","DOI":"10.1136\/bmj.1.4139.734"},{"issue":"1","key":"1109_CR2","first-page":"62","volume":"46","author":"E Lozinski","year":"1942","unstructured":"Lozinski E, Frohlich LI (1942) Resistance to Insulin. 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