Having a genetic tendency for reduced insulin production and unhealthy fat distribution plays a significant role in the early development of type 2 diabetes among British Asian individuals. Recent findings from Queen Mary University of London highlight that these genetic traits contribute to the quicker onset of health issues, an earlier requirement for insulin therapy, and a diminished effectiveness of certain treatments.
The results, shared in Nature Medicine, emphasize the importance of understanding how genetic differences among various population groups can affect the emergence and progression of diseases, as well as patient responses to treatment.
Researchers from Queen Mary used data from the Genes & Health cohort, which is a community-focused research initiative involving over 60,000 volunteers of British-Bangladeshi and British-Pakistani descent who have graciously donated their DNA for studies. The team successfully linked this genetic data with NHS health records for 9,771 individuals diagnosed with type 2 diabetes and 34,073 controls without diabetes, aiming to uncover why South Asians tend to develop type 2 diabetes at a younger age and often with a normal body mass index compared to white Europeans.
Unlike earlier studies that included minimal South Asian representation, this research applied partitioned polygenic scores (pPS) to identify the specific genetic markers that contribute to type 2 diabetes in people with South Asian ancestry.
Key findings from the study include:
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Genetic markers in South Asians: The earlier occurrence of type 2 diabetes in South Asians is closely associated with genetic markers that result in lower insulin production and undesirable fat distribution patterns leading to obesity. The most crucial genetic marker tied to the early onset of type 2 diabetes in South Asians is linked to the pancreas’s beta cells’ reduced ability to produce insulin. This marker also heightens the risk of gestational diabetes and its progression to type 2 diabetes post-pregnancy.
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Treatment responses: The genetic markers identified offer key insights into how different individuals may react to type 2 diabetes treatments. For instance, those with a high genetic predisposition for low insulin production showed lower responsiveness to common medications like sodium-glucose co-transporter 2 inhibitors and were more likely to need insulin therapy.
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Identification of a high genetic-risk group: The study recognized a distinct group of individuals exhibiting extreme genetic markers for both low insulin production and negative fat distribution. Those individuals were found to develop type 2 diabetes approximately 8 years earlier and at a lower body mass index. Over time, they were more likely to require insulin treatment and faced higher risks of diabetes-related complications, such as eye and kidney ailments.
Sarah Finer, Clinical Professor in Diabetes and Honorary Consultant in Diabetes at Queen Mary University of London, remarked: “Thanks to the involvement of numerous British Bangladeshi and British Pakistani volunteers in Genes & Health, we’ve uncovered vital insights into why young, slim individuals may develop type 2 diabetes. This research underscores the necessity to move away from a generic management approach for type 2 diabetes, paving the way for more targeted treatments that could effectively address the condition and lessen the occurrence of diabetes complications.”
Dr. Moneeza K. Siddiqui, a Lecturer in Genetic Epidemiology at Queen Mary University of London, stated: “We have yet to determine if genetic tools are essential for delivering precision medicine in South Asian populations or if we can make better use of existing tests like C-peptide, which can be easily measured through a blood test. Genes & Health will play a crucial role in future initiatives to develop precision medical approaches that can yield tangible benefits for South Asian communities facing type 2 diabetes challenges.”
Individuals of South Asian descent are often underrepresented in genetic research studies. The Genes & Health initiative at Queen Mary encompasses a community-based cohort comprising over 60,000 British-Bangladeshi and British-Pakistani volunteers who have provided genetic data and linked it to NHS health records for research purposes. This study has already resulted in significant findings aimed at enhancing health outcomes for British South Asians.
This research received support from Barts Charity and Wellcome.
