Differential Pathophysiological Drivers of Susceptibility to Type 2 Diabetes and Metabolic Dysfunction–Associated Steatotic Liver Disease: Ethnic Differences in Insulin Dynamics, Whole-Body Fat Metabolism, and Organ-Specific Lipid Deposition

Cuthbertson, D ORCID: 0000-0002-6128-0822, Whyte, M, Henney, A ORCID: 0000-0002-8066-9470, Alam, U ORCID: 0000-0002-3190-1122, Goff, L, Fielding, B and Umpleby, A (2026) Differential Pathophysiological Drivers of Susceptibility to Type 2 Diabetes and Metabolic Dysfunction–Associated Steatotic Liver Disease: Ethnic Differences in Insulin Dynamics, Whole-Body Fat Metabolism, and Organ-Specific Lipid Deposition Obesity Reviews. e70104-. ISSN 1467-7881, 1467-789X

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Abstract

Introduction: This narrative review explores the epidemiological evidence and potential underlying pathophysiological defects underlying the disproportionately greater risk of Type 2 diabetes (T2D) and cardiometabolic disease in people of South Asian and African Caribbean ancestry compared with White Europeans. Differences in (i) insulin dynamics, (ii) body composition and liver and pancreas triglyceride accumulation, and (iii) dysregulated fat metabolism likely contribute to this obesity-related susceptibility. Insulin Dynamics: 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. Body Composition: 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. Dysregulated Fat Metabolism: Dysregulated fat metabolism in adipose tissue/liver may increase serum fatty acids and triglyceride concentrations exposing non-adipose tissues to increased lipid. Differential T2D susceptibility likely reflects diverse but ethnic group–specific metabolic phenotypes representing genetic and environmentally mediated pathophysiological traits, consistent with the “palette” model of T2D.

Item Type:	Article
Uncontrolled Keywords:	diabetes, insulin resistance, metabolic dysfunction-associated steatotic liver disease, obesity
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences > Cardiovascular & Metabolic Medicine
Depositing User:	Symplectic Admin
Date Deposited:	18 Feb 2026 15:50
Last Modified:	14 Mar 2026 13:37
DOI:	10.1111/obr.70104
Open Access URL:	https://doi.org/10.1111/obr.70104
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3197111
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