“The study highlights genetic similarities and differences between different forms of type 2 diabetes in India and Europe. We see this article as an exciting new step towards a better understanding of the development of type 2 diabetes in India”, says Rashmi Prasad, associate professor in genomics, diabetes, and endocrinology at Lund University Diabetes Centre (LUDC).

Rashmi Prasad is one of the researchers behind an acclaimed study from 2018 that showed that diabetes can be divided into five subgroups based on how the disease develops. In 2021, she and her colleagues at LUDC contributed to a new study in Nature Genetics that demonstrated that there are genetic differences between the four forms of type 2 diabetes in Sweden. The new study, published in The Lancet Regional Health – Southeast Asia, confirms that the classification system is applicable on a cohort in western India. The results are based on clinical data from 2217 patients and genome-wide associations studies (GWAS) and a genetic risk score analysis (GRS) on 821 people with type 2 diabetes from a study in western India. 

“The characteristics of all the subgroups reflected those seen in European people with diabetes. We could also confirm our previous findings that have shown that a certain form of type 2 diabetes that is characterised by relatively low BMI is the most common form of the disease in India”, says Rashmi Prasad.

Early life undernutrition

The subgroup in question is called SIDD and this is a form of type 2 diabetes that is also characterised by early onset, low insulin secretion, and poor metabolic control. Of all the participants with type 2 diabetes in the Indian study, 47 percent were classified as belonging to the SIDD grouppatients. Previous studies on populations in Sweden have shown that MARD, which is characterised by late onset, is the most common form of diabetes among Swedish people.

“Early life undernutrition in Indians may be a major contribution to early onset of type 2 diabetes, and this may be why we see this difference in the distribution of patients between Sweden and India. The knowledge may be used to prevent the disease in India, which has the second highest number of diabetes worldwide after China. Our findings suggests that efforts to prevent malnutrition in Indians may also prevent type 2 diabetes”, says Rashmi Prasad.  

Vitamin B12 deficiency

The second largest group in India was MOD, a group which is characterised by obesity, early onset, and a relatively mild disease progression. The Indian group of people in the MOD group were associated with genetic variants for vitamin B12 deficiency, and this was not seen in the Swedish group of people in the MOD group. Vitamin B12 is obtained from animal foods, such as meat and dairy products. B12 deficiency is common in Indian people and is associated with vegetarian food habits. 

“It’s an interesting example of genetic differences between the Indian and Swedish groups in our study. This finding suggests that the causes of the disease differ between the two populations. Vitamin B12 deficiency may be a factor that drives the disease in the Indian MOD group”, says Rashmi Prasad, who is originally from India.

Rashmi Prasad has led the team of researchers together with professor Chittaranjan S Yajnik at King Edward Memorial (KEM) Hospital and Research Centre in Pune, India. The research exchange was supported by the Swedish Research Council and the Department of Science and Technology (DST) in India. The team would now like to carry out large-scale studies to unravel the characteristics of type 2 diabetes in India.

“Since ancient times physicians have experienced the heterogeneity of diabetes, and our systematic classification may help individualise the treatment and improve outcomes. Type 2 diabetes is a rapidly growing disease burden in India, and many Indians are being diagnosed at a younger age than before. Research like ours will help tackle the causes of the disease and is a step towards prevention”,  says Chittaranjan S Yajnik, who is a medical doctor and director of the diabetes unit at KEM Hospital.