Genetic Drivers of Early-Onset Type 2 Diabetes in South Asians Revealed

A study recently published in Nature Medicine highlights genetic factors that contribute to early-onset type 2 diabetes in South Asians, a population disproportionately affected by the condition. Conducted by researchers at Queen Mary University of London, the study identifies key genetic predispositions, including reduced insulin production and unhealthy fat distribution, as critical drivers of the disease. These findings also suggest that South Asians experience faster disease progression and more treatment challenges compared to other populations, underscoring the need for tailored, precision-based care.

New Genetic Evidence Specific to South Asians

The research leveraged data from the Genes & Health cohort, one of the largest community-based genetic studies involving South Asian populations. Over 60,000 British-Bangladeshi and British-Pakistani participants contributed DNA and linked their genetic data to NHS health records. Researchers analyzed 9,771 individuals with type 2 diabetes and 34,073 without the condition. By applying a technique known as partitioned polygenic scores (pPS), they were able to uncover genetic patterns specific to South Asians, which had previously been underexplored in diabetes research.

A major finding was the strong link between early diabetes onset and genetic signatures associated with reduced pancreatic beta-cell function, leading to lower insulin production. Additionally, patterns of fat distribution—often unrelated to high body mass index (BMI)—emerged as a significant risk factor, helping explain why diabetes affects some South Asians at a younger age and lower BMI compared to white Europeans.

Key Findings and Their Implications

Genetic Risks Identified

The study pinpointed genetic profiles that not only predispose South Asians to diabetes earlier in life but also to severe complications. Those with extreme risk profiles tended to develop diabetes an average of eight years earlier and were more likely to experience complications such as kidney and eye diseases.

Treatment Challenges

Another key finding was the variation in treatment responses among South Asians. Individuals with genetic markers tied to low insulin production were less responsive to common medications, such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, and more likely to require insulin therapy earlier in the disease course.

Fat Distribution as a Risk Factor

Beyond insulin production, unfavorable fat distribution emerged as a significant genetic marker for diabetes in this population. Unlike trends observed in other ethnic groups, South Asians can develop diabetes despite having a normal BMI, highlighting the limitations of traditional metrics in assessing risk for this group.

Moving Toward Precision Medicine

“This work also tells us how important it is to move away from a ‘one-size-fits-all’ approach to managing type 2 diabetes,” said Professor Sarah Finer, Clinical Professor in Diabetes at Queen Mary University of London. “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, added, “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.”

Why It Matters

South Asians have historically been underrepresented in genetic studies, despite having higher rates of early-onset type 2 diabetes and related complications. By focusing on this population, the study offers important insights into how tailored approaches can improve health outcomes. These findings pave the way for more inclusive research, better diagnostic tools, and more effective treatments designed to address the unique genetic and physiological risks faced by South Asians.

Queen Mary’s Genes & Health cohort continues to provide a foundation for discoveries that could transform diabetes care and narrow health disparities for British-Bangladeshi and British-Pakistani communities.