Ethnic differences in susceptibility to fatty liver, cardiovascular disease and type 2 diabetes in white Europeans, South Asians and African-Caribbean

Type 2 diabetes (T2D) and cardiovascular disease are more prevalent in people of South Asian or African-Caribbean descent living in the UK, compared to White Europeans.

Yet UK guidelines for cardiometabolic disease management have primarily been developed in White Europeans, exacerbating health inequalities.

We hypothesise that two distinct pathophysiological models explain inter-ethnic differences in the manifestation of cardiovascular and metabolic disease.

In South Asian people, increased ectopic fat, including fatty liver, underlies greater insulin resistance resulting in secondary hyperinsulinaemia.

In African-Caribbean people, the primary defect is peripheral hyperinsulinaemia – due to lower hepatic insulin clearance. This results in less liver fat but greater peripheral exposure to insulin and secondarily, insulin resistance.

We will explore how these two models drive the disparities in the cardiometabolic risks associated with obesity between UK people of South Asian, African-Caribbean and White European descent through: • metabolic testing using mixed-meal assessments of post-prandial fat metabolism, insulin resistance, insulin secretion and insulin clearance. • body composition phenotyping using abdominal/cardiac MRI in three age- and fat-mass matched ethnic groups.

This work will provide an evidence base underpinning ethnicity-specific guidance for managing T2D risks and outcomes, improving the lives of those from ethnic minority groups living with T2D.