Regional Health Southeast Asia
Study on genetic similarities and differences between subgroups of type 2 diabetes in India and Europe
Pune (Voice News Service): A collaborative research between KEM Hospital Research Centre, Pune and Lund University in Sweden on genetic similarities and differences between subgroups of type 2 diabetes in India and Europe has been published in The Lancet Regional Health – Southeast Asia in May 2023. This is the second publication under this collaboration. The knowledge will help improve treatment of the disease in India, where type 2 diabetes represents a growing disease burden. The research exchange was supported by the Department of Science and Technology (DST) in India and the Swedish Research Council in Sweden. The collaborative research was led by Dr Rashmi Prasad, Associate Professor in Genomics, Diabetes, and Endocrinology at Lund University Diabetes Centre (LUDC) together with Prof. Dr. Chittaranjan S Yajnik, Director & Consultant – Diabetes Unit at King Edward Memorial (KEM) Hospital and Research Centre in Pune, India. The new study confirms that the genetic scores developed in European patients are applicable on patients in western India, though there are differences in the associations between the two populations. The results are based on clinical data from 2217 patients with type 2 diabetes from the WellGen study in western India, genetic data was available in 821 people of this group.
Researchers at Lund University, Malmo, Sweden have shown that diabetes can be divided into five subgroups, including SAID (severe auto-immune diabetes), SIDD (severe insulin-deficient diabetes), SIRD (severe insulin-resistant diabetes), MOD (mild obesity-related diabetes) and MARD (mild age-related diabetes). SAID is also known as type 1 diabetes, the remaining four subgroups belong to type 2 diabetes. This paper was published in the Lancet Diabetes & Endocrinology in 2018. Dr Rashmi Prasad is one of the authors of this acclaimed study. The paper generated a lot of interest and was replicated in many other populations which confirmed that diabetes can be divided into the above subgroups based on clinical and biochemical characteristics and that this classification is useful to guide treatment and may help predict complications. In 2021, the Swedish group at LUDC published a new study in the Nature Genetics that demonstrated genetic differences between the four subgroups of type 2 diabetes in Sweden.
Dr Yajnik said that our first study under this collaboration was published in Diabetologia in 2021 and was on people who were diagnosed with type 2 diabetes below 45 years of age. We confirmed the 4 subgroups in the Indian type 2 diabetes patients but the proportion of subgroups was different in Indian and Swedish cohorts. We found that the commonest subgroup of diabetes in Indian cohort was severely insulin deficient (SIDD), while in Sweden it was mild obesity-related (MOD) and associated with insulin resistance. This difference could be due to genetic or environmental factors. There are a number of differences in the environment and lifestyle of these two populations which reflect in body size and metabolism. These differences start from before conception and persist through lifecourse.
The collaboration therefore decided to study genetics of type 2 diabetes subgroups in a larger cohort of Indian and Swedish patients, not restricting to those diagnosed below the age of 45 years. The largest subgroup was still the SIDD. We used genetic markers of type 2 diabetes and a number of associated characteristics (obesity, insulin secretion, insulin resistance, lipid abnormalities, etc.). We found that the genetic scores developed in Europeans are usable in Indians and there are broad similarities in associations when type 2 diabetes is considered as a single group. However, there are subtle differences in genetic associations of the subgroups between Indian and Swedish patients with type 2 diabetes. This paints a complex picture of type 2 diabetes and a need for further studies of genetic and environmental factors which contribute to the metabolic disorder and its different mechanisms and manifestations in different populations. For example, when we looked at the genetic score for the commonly used obesity parameter BMI (body mass index, weight / height2) Indian and Swedish patients had similar scores but for each score Indians have a much lower BMI, suggesting that a number of environmental factors might prevent Indians from expressing their genetic potential into a physical characteristic. Undernutrition in Indians for many generations may be responsible.
Two such interesting differences between Indian and Swedish cohorts refer to deposition of fat in the liver and association with vitamin B12 status. A number of studies in India and abroad have shown that increased liver fat is a characteristic feature of Indian type 2 diabetes patients. In our study we found associations of genetic risk score for liver fat with 3 out of 4 subgroups in Indian cohort but with none in Swedish. Vitamin B12 deficiency is common in India, related to vegetarian food habits but is uncommon in Sweden where people are traditionally meat eaters. Our previous studies had found a strong association of FUT genes with vitamin B12 status. Interestingly, FUT genes was associated with type 2 diabetes and with MOD subgroup only in Indians but not in the Swedish cohort. Further studies are clearly needed to understand the mechanisms of such associations and their implications for prevention and treatment of type 2 diabetes. One such study has already started in Pune. In the PRIYA (Pune Rural Intervention in Young Adolescents) trial, we supplemented young rural adolescents with vitamin B12 and other micronutrients to reduce risk of diabetes in their children. Initial reports showed a beneficial effect on their brain development, future studies will investigate the effects on risk of diabetes.
Dr Rashmi Prasad, who is originally from India, said that we found interesting examples of genetic differences between the Indian and Swedish groups in our study. This suggests that the causes of type 2 diabetes differ between the two populations. Vitamin B12 deficiency may be one of the factors that drives the pathogenesis of the MOD subgroup in Indians.
Type 2 diabetes is a rapidly growing disease burden in India. Ancient Indian physicians had observed heterogeneity of diabetes. Research like ours will help better understand the causes of diabetes and is a step towards prevention and effective treatment, says Chittaranjan S Yajnik, who is a medical doctor and director of the Diabetes Unit at KEM Hospital and Research Centre, Pune.
Photo caption: India-Sweden diabetes collaborative group. L to R: Dr Pranay Goel, Pooja Kunte, Rucha Wagh, Dr Chittaranjan Yajnik, Dr Sharvari Shukla, Dr Rashmi Prasad, Dr Leif Groop.
Dr Chittaranjan S Yajnik, MD, FRCP
Director, Diabetes Unit, KEM Hospital & Research Centre, Pune, India
