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

A genetic predisposition to lower insulin production and less healthy fat distribution are major causes of early-onset type 2 diabetes (T2D) in British Asian people, according to new research published in Nature Medicine. The study also shows that these genetic factors lead to faster development of health complications, earlier need for insulin treatment, and a weaker response to some medications. The results reinforce the need to understand how genetic variation across different population groups can influence the onset of diseases, treatment responses, and disease progression.

Published:

The study used data from the Genes & Health cohort, a community-based study of more than 60,000 British-Bangladeshi and British-Pakistani volunteers who generously provided their DNA for genetic research. Researchers linked genetic information to NHS health records in 9771 volunteers with a T2D diagnosis and 34,073 diabetes-free controls, to understand why South Asians develop T2D at a younger age and often with normal body mass index, compared with white Europeans. While previous studies include very few people of South Asian heritage, this research used partitioned polygenic scores (pPS) to reveal the underlying genetic signatures causing T2D specifically in people with South Asian ancestry.

Key discoveries include:

  • Genetic signatures: The younger age of T2D 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 T2D, and at a young age, is a reduced ability of pancreatic beta cells to produce insulin. This signature also increases the risk of gestational diabetes and the progression of gestational diabetes to T2D after pregnancy.
  • Treatment responses: The genetic signatures identified in the study provide vital clues about how different people may respond to T2D 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, who were found to develop T2D 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.

 

Sam Hodgson, Alice Williamson, Margherita Bigossi, Daniel Stow, Benjamin M  Jacobs, Miriam Samuel, Joseph Gafton, Julia Zöllner, Marie Spreckley, Genes & Health Research Team, Claudia Langenberg, David A. van Heel, Rohini Mathur, Moneeza K Siddiqui, Sarah Finer. Genetic basis of early onset and progression of type 2 diabetes in south Asians”. Nature Medicine. 26 November 2024. https://www.nature.com/articles/s41591-024-03317-8

 

 

 

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