Identification of genetic factors of type 2 diabetes mellitus risk in South Asian populations

Abstract

People of South Asian ancestry are more likely to develop type 2 diabetes mellitus (T2DM) at a younger age and lower BMI than people of European ancestry. The reasons for this fact are poorly understood, as the majority of genetic research on T2DM has been performed in white European populations. Now, a study in Nature Medicine has used partitioned polygenic risk scores (pPS) to uncover the genetic pathways that predispose people of British Pakistani and British Bangladeshi origin to T2DM and gestational diabetes mellitus (GDM).

The researchers next assessed whether pPS could be used to predict the responses of patients of South Asian heritage to antidiabetic medication. They found that higher pPS scores for lipodystrophy and β-cell insulin dysfunction was associated with a reduced response to metformin and sodium–glucose co-transporter 2 inhibitors and an increased likelihood of progressing to insulin treatment. Finally, the study identified that individuals with ‘extreme’ (top decile) pPS signatures for insulin deficiency and lipodystrophy had a higher risk of developing T2DM than the overall study population, were diagnosed with T2DM 8 years earlier than those with low pPS in those categories and were more likely to develop complications such as diabetic retinopathy.