{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:47:05Z","timestamp":1792118825983,"version":"4.4.0"},"reference-count":41,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2017,3,21]],"date-time":"2017-03-21T00:00:00Z","timestamp":1490054400000},"content-version":"vor","delay-in-days":76,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"name":"EU Horizon 2020 project EpoS","award":["634413"],"award-info":[{"award-number":["634413"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,4,1]]},"abstract":"<jats:p>In the transition from normal glucose tolerance (NGT) to type 2 diabetes mellitus (T2DM), the role of \u03b2-cell dysfunction and peripheral insulin resistance (IR) is well established. However, the impact of dysfunctional adipose tissue has not been fully elucidated. The aim of this study was to evaluate the role of resistance to the antilipolytic effect of insulin (adipose tissue IR [Adipo-IR]) in a large group of subjects with NGT, impaired glucose tolerance (IGT), and T2DM. Three hundred two subjects with varying glucose tolerance received an oral glucose tolerance test (OGTT) and euglycemic insulin clamp. We evaluated Adipo-IR (fasting and mean OGTT plasma free fatty acid [FFA] \u00d7 insulin concentrations), peripheral IR (1\/[Matsuda index] and (M\/I)\u22121 value), and \u03b2-cell function (calculated as the ratio of the increment in plasma insulin to glucose [OGTT\/IR (\u0394I\/\u0394G \u00f7 IR)]). Fasting Adipo-IR was increased twofold in obese subjects with NGT and IGT versus lean subjects with NGT (8.0 \u00b1 1.1 and 9.2 \u00b1 0.7 vs. 4.1 \u00b1 0.3, respectively) and threefold in subjects with T2DM (11.9 \u00b1 0.6; P &amp;lt; 0.001). Progressive decline in \u0394I\/\u0394G \u00f7 IR was associated with a progressive impairment in FFA suppression during OGTT, whereas the rise in mean plasma glucose concentration only became manifest when subjects became overtly diabetic. The progressive decline in \u03b2-cell function that begins in individuals with NGT is associated with a progressive increase in FFA and fasting Adipo-IR.<\/jats:p>","DOI":"10.2337\/db16-1167","type":"journal-article","created":{"date-parts":[[2017,1,4]],"date-time":"2017-01-04T21:20:31Z","timestamp":1483564831000},"page":"815-822","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":310,"title":["Role of Adipose Tissue Insulin Resistance in the Natural History of Type 2 Diabetes: Results From the San Antonio Metabolism Study"],"prefix":"10.2337","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-1651","authenticated-orcid":false,"given":"Amalia","family":"Gastaldelli","sequence":"first","affiliation":[{"name":"University of Texas Health Science Center at San Antonio, San Antonio, TX"},{"name":"Cardiometabolic Risk Laboratory, Institute of Clinical Physiology, National Research Council, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Gaggini","sequence":"additional","affiliation":[{"name":"Cardiometabolic Risk Laboratory, Institute of Clinical Physiology, National Research Council, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph A.","family":"DeFronzo","sequence":"additional","affiliation":[{"name":"University of Texas Health Science Center at San Antonio, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2017,1,4]]},"reference":[{"key":"2022031210351520100_B1","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1210\/jc.2004-0395","article-title":"Adipose tissue as an endocrine organ","volume":"89","author":"Kershaw","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031210351520100_B2","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.2337\/db06-0263","article-title":"Adipose tissue: 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