New study reveals genetic drivers of early onset type 2 diabetes in South Asians 

UNDER STRICT EMBARGO UNTIL 10.00AM (UK TIME) ON 26 NOVEMBER 2024 

New study reveals genetic drivers of early onset type 2 diabetes in South Asians   

Peer reviewed | Observational study | People 

A genetic predisposition to having lower insulin production and less healthy fat distribution are major causes of early-onset type 2 diabetes in British Asian people. According to new research from Queen Mary University of London, these genetic factors also lead to quicker development of health complications, earlier need for insulin treatment, and a weaker response to some medications. 

The findings, published today in Nature Medicine, reinforce the need to understand how genetic variation across different population groups can influence the onset of diseases, treatment responses, and disease progression. 

Queen Mary researchers used data from the Genes & Health cohort, a community-based study of more than 60,000 British-Bangladeshi and British-Pakistani volunteers who have generously provided their DNA for genetic research. The researchers securely linked genetic information to NHS health records in 9,771 Genes & Health volunteers with a type 2 diabetes diagnosis and 34,073 diabetes-free controls to understand why South Asians develop type 2 diabetes at a younger age and often with normal body mass index, compared to white Europeans.   

In contrast to previous studies which included very few people of South Asian heritage, this research used partitioned polygenic scores (pPS) to reveal the underlying genetic signatures causing type 2 diabetes specifically in people with South Asian ancestry.  

Key discoveries from the study include:  

• Genetic signatures in south Asians: The younger age of onset in South Asians is strongly linked to genetic signatures that lead to both lower insulin production and unfavourable patterns of body fat distribution and obesity.  The most significant genetic signature influencing whether a South Asian person develops type 2 diabetes, and at a young age, is a reduced ability of pancreatic beta cells to produce insulin. This genetic signature also increases the risk of gestational diabetes and the progression of gestational diabetes to type 2 diabetes after pregnancy.  

• Treatment responses: The genetic signatures identified in the study provide vital clues about how different people may respond to type 2 diabetes treatments. For example, individuals with high genetic risk for low insulin production were less likely to respond to common medications such as sodium-glucose co-transporter 2 inhibitors and were more likely to require insulin therapy. 

• High genetic-risk group identified: The study identified a subset of people with extreme genetic signatures for both low insulin production and unfavourable fat distribution. These individuals were found to develop type 2 diabetes an average of 8 years earlier and at lower body mass index. Over time, these individuals were more likely to need insulin treatment and were at higher risk for diabetes complications such as eye and kidney disease.  

Sarah Finer, Clinical Professor in Diabetes Honorary Consultant in Diabetes at Queen Mary University of London, said: “Thanks to the participation of so many British Bangladeshi and British Pakistani volunteers in Genes & Health, we have found important clues as to why type 2 diabetes may develop in young, slim individuals. This work also tells us how important it is to move away from a “one-size-fits-all” approach to managing type 2 diabetes, and we hope that this will allow us to find ways to offer more precise treatments that treat the condition more effectively and reduces the development of diabetes complications.” 

Dr Moneeza K. Siddiqui, Lecturer in Genetic Epidemiology at Queen Mary University of London, said: “We don’t yet know whether genetic tools will be needed to deliver precision diabetes medicine in south Asian populations, or whether we can better and more widely use existing laboratory tests such as C-peptide which can be measured in a simple blood test. Genes & Health will contribute to future efforts to ensure that precision medicine approaches are developed and bring real benefits to south Asian communities living with, and at risk of, type 2 diabetes.” 

People with South Asian heritage are underrepresented in genetic studies. Queen Mary’s Genes & Health is a community-based cohort of more than 60,000 British-Bangladeshi and British-Pakistani volunteers who have provided their genetic information and linkage to NHS health data for research. The study has so far led to major discoveries that improve the health outcomes of British South Asians.   

This research was supported by Barts Charity and Wellcome. 

ENDS  

NOTES TO EDITORS  

Contact  

Sophia Prout   

Faculty Communications Manager – Medicine and Dentistry   

Queen Mary University of London   

Email: s.prout@qmul.ac.uk or press@qmul.ac.uk   

Honey Lucas   

Faculty Communications Officer – Medicine and Dentistry   

Queen Mary University of London   

Email: h.lucas@qmul.ac.uk or press@qmul.ac.uk   

Paper details:    

Sam Hodgson et al, “Genetic basis of early onset and progression of type 2 diabetes in south Asians”. Nature Medicine.  

DOI: 10.1038/s41591-024-03317-8 

Under strict embargo until 26 November 2024 at 10:00 (London time), 26 November 2024 at 05:00 (US Eastern Time) 

Available after publication at:   https://www.nature.com/articles/s41591-024-03317-8  

A copy of the paper is available upon request.  

Conflicts of interest:   None declared.

Funded by: Supported by Barts Charity and Wellcome. 

About Queen Mary University of London 

www.qmul.ac.uk      

At Queen Mary University of London, we believe that a diversity of ideas helps us achieve the previously unthinkable.   

Throughout our history, we’ve fostered social justice and improved lives through academic excellence. And we continue to live and breathe this spirit today, not because it’s simply ‘the right thing to do’ but for what it helps us achieve and the intellectual brilliance it delivers.     

Our reformer heritage informs our conviction that great ideas can and should come from anywhere. It’s an approach that has brought results across the globe, from the communities of east London to the favelas of Rio de Janeiro.     

We continue to embrace diversity of thought and opinion in everything we do, in the belief that when views collide, disciplines interact, and perspectives intersect, truly original thought takes form.    

About Genes & Health  

https://www.genesandhealth.org/  

Genes & Health is one of the world’s largest community-based genetics research programmes, focusing on improving health outcomes for British Bangladeshi and British Pakistani communities through ground-breaking scientific discovery. 

About Barts Charity 

Barts Charity brings brilliant ideas, ground-breaking research and transformational healthcare to life in East London. Together with our partners, we make better healthcare possible, funding brilliant ideas and ground-breaking research to transform lives.  

As the dedicated charity for Barts Health NHS Trust, we support St Bartholomew’s, Whipps Cross, Newham, Royal London, and Mile End hospitals, as well as the Faculty of Medicine and Dentistry at Queen Mary University of London. We also support researchers at the School of Health & Psychological Sciences at City, University of London. Visit https://www.bartscharity.org.uk 

About Wellcome 

Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health.