Comparing the physiological effects of low-calorie diets in South Asian and White European individuals with early-onset Type 2 Diabetes

140,000 people in England, and >260 million people worldwide are diagnosed with Type 2 Diabetes (T2D) before the age of 40-years. Compared to diagnosis in later-life, early-onset T2D has a more severe course, with faster progression to needing insulin, higher rates of diabetes-complications and a life-expectancy that is shortened by approximately 14 years. Worryingly this age bracket also shows the fastest rise in incidence of T2D. In 2016, the DiRECT study showed that after following a 12-week low-calorie diet, 46% people with T2D were in remission a year later, meaning that sugar levels were back to normal without needing medications. This important finding has led to the Path-to-Remission programme, which is available nationally on the NHS to individuals aged 18-65-years who are offered a similar low-calorie diet. However, 99% of those studied in DiRECT were White European, and only 7 out of 298 people in the trial were aged <40-years (2.3%). Whether similar results are observed in younger age groups and other ethnicities is a knowledge gap concluded by the study authors, a key research priority of Diabetes UK, and a research priority identified by the international consensus group on the clinical translation of precision diabetes medicine. Why study younger age groups and ethnic minorities? A third of individuals with early-onset T2D in England are of Asian ethnicity, and preliminary unpublished data from the Path-to-Remission programme show that the chance of remission is lower in those <40-years compared to older age groups, and lower in Asians of all ages compared to White Europeans. The likelihood of achieving remission following a low-calorie diet is closely linked to the ability of the pancreas to produce insulin. Studies have shown lower insulin production from the pancreas in those diagnosed with T2D at a younger age, and in South Asian individuals compared to White European individuals. It is not clear if this is due to the nature of their diabetes, genetics, or compliance with the diet. Aims and objectives The objectives of this study are: 1. To compare the physiological effect of a low-calorie diet in South Asian and White European individuals with early-onset T2D 2. To investigate whether ethnic differences in physiological response may result from the features of their diabetes, genetics, or dietary compliance. I will study White European and South Asian individuals with early-onset T2D before and after participating in the NHS Path-to-Remission programme, studying: • Clinical features • Insulin secretion from the pancreas • Liver and pancreas fat content • Genetic risk for low pancreatic insulin secretion • Compliance with the low-calorie diet. This work will expand the evidence base for low-calorie diets in achieving remission of T2D in those with early-onset T2D and unpick underlying ethnic differences in South Asian T2D populations, who are currently under-represented in research. Understanding age-based and ethnicity-based differences in the response to diabetes-interventions is critical in progressing towards a precision-medicine approach to diabetes remission. An exploration of how individual physiology, genetics and programme adherence contribute to the observed differences in remission rates following low-calorie diets will facilitate future research to address these differences and will further our understanding of the parameters that predict diabetes remission, promoting both more informed patient choice and the allocation of low-calorie diets to produce maximum benefit.