People of African and Caribbean heritage experience a disproportionate burden of type 2 diabetes, with higher prevalence, younger age of onset, and poorer clinical outcomes compared with white European populations. Notably, this excess risk occurs despite lower levels of visceral and intra-organ fat, a phenomenon often referred to as the African Paradox. These observations suggest fundamental ethnic distinctions in the physiological mechanisms underlying type 2 diabetes that are not adequately captured by prevailing disease models.

This plenary talk will focus on insights from the Diabetes UK–funded South London Diabetes & Ethnicity Phenotyping study, a pioneering programme of experimental medicine designed to elucidate the physiological drivers of diabetes risk in people of African ancestry. The talk will outline how advanced metabolic phenotyping approaches—including stable isotope techniques and magnetic resonance imaging—have been used to interrogate fat metabolism, insulin resistance, β-cell function, and intra-organ lipid deposition.

The central focus will be on evidence demonstrating that type 2 diabetes in people of African ancestry is characterised by distinct pathophysiological features, particularly reduced hepatic insulin clearance, as a primary defect, leading to hyperinsulinaemia, alongside relative sparing of visceral and intra-organ fat. These findings challenge the long-standing paradigm that insulin resistance is the primary initiating defect in type 2 diabetes and highlight the need to reconsider current physiological models.

The talk will conclude by exploring the broader implications of these findings for metabolic physiology and clinical practice, including their relevance to current intervention strategies such as dietary remission approaches. By highlighting the importance of ethnic diversity in physiological research, this work underscores the need for mechanism-based, tailored strategies to improve equity in diabetes prevention and treatment.