Genetic vulnerability for low insulin, unhealthy fat major causes for diabetes in South Asians: Study

New Delhi: Genetic vulnerabilities of producing lower levels of insulin and having an unhealthy distribution of fat could be major causes for South Asians developing type 2 diabetes at a younger age, according to a UK-based study that looked at participants of Bangladeshi and Pakistani origin.

Researchers from Queen Mary University, UK, said that while South Asians are known to develop diabetes early in life and often whilst having a normal body mass index, reasons for this are poorly understood because genetic research is largely focused on European ancestry groups.

For the study, published in the journal Nature Medicine, the researchers used data from the Genes and Health cohort, a community-based study of British-Bangladeshi and British-Pakistani volunteers. Nearly 9,800 had a diagnosis of diabetes, while over 34,000 did not.

The participants’ genetic information was linked to records maintained by the UK’s National Health Service. Thus, a genetic score — ‘partitioned polygenic score’ — was developed for each individual.

The team found that the most significant genetic signature is that of a reduced ability of pancreatic beta cells to produce the hormone insulin, which regulates blood sugar levels.

The signature also increases the risk of gestational diabetes and progression of the pregnancy complication to type 2 diabetes after pregnancy, they said.

The genetic signatures identified provide vital clues about how different people may respond to diabetes treatments, the researchers added.

For example, individuals having a high genetic risk for producing low insulin were less likely to respond to common medications such as sodium-glucose co-transporter 2 (SGLT2) inhibitors and were more likely to require insulin therapy, the team explained.

SGLT2 is a protein in the kidneys that reabsorbs glucose from the urine. SGLT2 inhibitors are a class of drugs that help one manage blood sugar.

The findings of genetic nature will help “find ways to offer more precise treatments that treat the condition more effectively and reduce the development of diabetes complications,” author Sarah Finer, from Queen Mary University of London, said.

“Genetic predisposition to insulin deficiency and lipodystrophy in British Pakistani and British Bangladeshi individuals is associated with earlier onset of (type 2 diabetes), faster progression to complications, insulin dependence and poorer response to medication,” the authors wrote.

The researchers also identified a subset of people having extreme genetic signatures for both low insulin production and unfavourable fat distribution.

These individuals were found to develop diabetes eight years earlier on average and at a lower body mass index, compared to those at a low genetic risk, the team said.

Over time, these individuals are more likely to need insulin treatment and are at higher risk for diabetes complications such as eye and kidney disease, the authors said.