Young onset diabetes in Asian Indians is associated with lower measured and genetically determined beta-cell function: an INSPIRED study

Background South Asians have higher risk of type 2 diabetes compared to white Europeans and a younger age of onset. Reasons for the younger age of onset in relation to beta-cell function and insulin sensitivity are under-explored. Methods Two cohorts of Asian Indians, ICMR-INDIAB (Indian Council of Medical Research-INdia DIABetes Study) and DMDSC (Dr. Mohans Diabetes Specialties Centre) and one of white Europeans, ESDC (East Scotland Diabetes Cohort) were used. We examined the comparative prevalence of healthy, overweight, and obese BMI in young onset diabetes. We explored the role of clinically measured beta-cell function in diabetes onset in Asian Indians. Finally, the comparative distribution of a partitioned polygenic score (pPS) for risk of diabetes due to poor beta cell function was examined. Results Prevalence of young onset with normal BMI was 9.3% amongst white Europeans and 24%-39% amongst Asian Indians. In young diagnosed Asian Indians, after adjustment for family history of T2DM, sex, insulin sensitivity and HDL-c, stimulated C-peptide was 492pmol/mL (IQR: 353,616,P<0.0001) lower in lean compared to obese individuals. Asian Indians have lower genetically determined beta-cell function than white Europeans(P <0.0001). The pPS was associated with age of diagnosis in Asian Indians but not in white Europeans. The pPS explained 2% of variation in clinically measured beta cell function and 1.2%, 0.97%, and 0.36% of variance in age of diabetes amongst Asian Indians with normal, overweight, and obese BMI respectively. Conclusions Asian Indians have over two times the prevalence of lean BMI in young onset diabetes compared to white Europeans. This phenotype of lean, young onset diabetes appears driven in part by lower beta cell function. We demonstrate that Asian Indians with diabetes also have lower genetically determined beta cell function.