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Differences in (i) insulin dynamics, (ii) body composition and liver and pancreas triglyceride accumulation, and (iii) dysregulated fat metabolism likely contribute to this obesity\u2010related susceptibility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Insulin Dynamics<\/jats:title>\n                    <jats:p>Insulin resistance and hyperinsulinemia are key pathophysiological defects in T2D, although the primary defect is uncertain. Many believe that insulin resistance precedes compensatory hyperinsulinemia; much data suggest that hyperinsulinemia precedes insulin resistance. Hyperinsulinemia, related to reduced hepatic insulin clearance, may represent the primary defect in people of African Caribbean ancestry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Body Composition<\/jats:title>\n                    <jats:p>Ectopic fat, particularly visceral, liver, and pancreatic fat, is associated with impairments in insulin action\/secretion: Higher liver fat is specifically related to hepatic insulin resistance and higher pancreatic fat to impaired beta cell function. People of South Asian ancestry exhibit greater ectopic particularly liver fat, compared with White Europeans, and more severe insulin resistance, driving hyperinsulinemia. People of African Caribbean ancestry have lower visceral and liver fat and greater muscle mass.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Dysregulated Fat Metabolism<\/jats:title>\n                    <jats:p>Dysregulated fat metabolism in adipose tissue\/liver may increase serum fatty acids and triglyceride concentrations exposing non\u2010adipose tissues to increased lipid. Differential T2D susceptibility likely reflects diverse but ethnic group\u2013specific metabolic phenotypes representing genetic and environmentally mediated pathophysiological traits, consistent with the \u201cpalette\u201d model of T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/obr.70104","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T02:39:23Z","timestamp":1771295963000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Differential Pathophysiological Drivers of Susceptibility to Type 2 Diabetes and Metabolic Dysfunction\u2013Associated Steatotic Liver Disease: Ethnic Differences in Insulin Dynamics, Whole\u2010Body Fat Metabolism, and Organ\u2010Specific Lipid Deposition"],"prefix":"10.1111","volume":"27","author":[{"given":"Daniel\u00a0J.","family":"Cuthbertson","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Metabolic Medicine, 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