Having a genetic predisposition to insulin deficiency and abnormal fat distribution around the body may explain why South Asian people seem to be at particularly high risk for early onset type 2 diabetes, shows new U.K. research.
Current estimates suggest around 10% of adults between the age of 20 and 79 years have type 2 diabetes, but this prevalence is higher in people with South Asian ancestry with an average prevalence of approximately 13% worldwide and with rates as high as 30% in countries like Pakistan.
“Compared to individuals of European ancestry, South Asians tend to be diagnosed with type 2 diabetes at younger ages and with a lower body mass index,” wrote lead author Moneeza Siddiqui, PhD, a researcher and lecturer at Queen Mary University of London, and colleagues in the paper describing the work in the journal Nature Medicine.
“However, reasons for this are poorly understood because genetic research is largely focused on European ancestry groups.”
Siddiqui and colleagues created multi-ancestry partitioned polygenic risk scores to try and investigate why people of South Asian ancestry are at higher risk using data from the Genes and Health study. This cohort includes more than 60,000 British Bangladeshi and British Pakistani people.
The cohort includes 11,678 people with type 2 diabetes and 1,965 women who experienced gestational diabetes, as well as more than 34,000 without diabetes. The team analyzed the genetic data from the Genes and Health study participants and found genetic signatures characterizing type 2 diabetes risk.
In particular, having a high genetic risk score for low insulin and abnormal fat distribution around the body (lipodystrophy 1) was strongly linked to type 2 diabetes, gestational diabetes and younger age at diabetes diagnosis.
The results showed that people with high genetic risk for insulin deficiency had a worse response to a type of medication called a SGLT2 inhibitor and were more likely to progress from gestational diabetes to full blown type 2 diabetes.
People in the cohort at high genetic risk for both insulin deficiency and lipodystrophy were diagnosed with type 2 diabetes more than eight years earlier than those with low genetic risk and were more likely to have microvascular complications and a faster progression of their condition.
“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,” said Siddiqui in a press statement.
“Genes and Health will contribute to future efforts to ensure that precision medicine approaches are developed and bring real benefits to south Asian communities living with, and at risk of, type 2 diabetes.”
