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

Siddiqui, M. et al. (2022) Young-onset diabetes in Asian Indians is associated with lower measured and genetically determined beta cell function. Diabetologia, 65(6), pp. 973-983. (doi: 10.1007/s00125-022-05671-z) (PMID:35247066)

Abstract

Aims/hypothesis: South Asians in general, and Asian Indians in particular, have higher risk of type 2 diabetes compared with white Europeans, and a younger age of onset. The reasons for the younger age of onset in relation to obesity, beta cell function and insulin sensitivity are under-explored. Methods: Two cohorts of Asian Indians, the ICMR-INDIAB cohort (Indian Council of Medical Research-India Diabetes Study) and the DMDSC cohort (Dr Mohan’s Diabetes Specialties Centre), and one of white Europeans, the ESDC (East Scotland Diabetes Cohort), were used. Using a cross-sectional design, we examined the comparative prevalence of healthy, overweight and obese participants with young-onset diabetes, classified according to their BMI. 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. Replication of the genetic findings was sought using data from the UK Biobank. Results: The prevalence of young-onset diabetes with normal BMI was 9.3% amongst white Europeans and 24–39% amongst Asian Indians. In Asian Indians with young-onset diabetes, after adjustment for family history of type 2 diabetes, sex, insulin sensitivity and HDL-cholesterol, stimulated C-peptide was 492 pmol/ml (IQR 353–616, p<0.0001) lower in lean compared with obese individuals. Asian Indians in our study, and South Asians from the UK Biobank, had a higher number of risk alleles than white Europeans. After weighting the pPS for beta cell function, 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 the 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 BMI, or classified as overweight and obese BMI, respectively. Conclusions/interpretation: The prevalence of lean BMI in young-onset diabetes is over two times higher in Asian Indians compared with 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.

• Item Type: Articles
• Additional Information: This research was funded by the National Institute for Health Research (NIHR) (INSPIRED 16/136/102) using aid from the UK government to support global health research.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Siddiqui, M., Anjana, R.M., Dawed, A. Y., Martoeau, C., Srinivasan, S., Saravanan, J., Madanagopal, S. K., Taylor, A., Bell, S., Veluchamy, A., Pradeepa, R., Sattar, N., Venkatesan, R., Palmer, C. N.A., Pearson, E. R., and Mohan, V.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Diabetologia
• Publisher: Springer
• ISSN: 0012-186X
• ISSN (Online): 1432-0428
• Published Online: 05 March 2022
• Copyright Holders: Copyright © 2022 The Author(s)
• First Published: First published in Diabetologia 65(6): 973-983
• Publisher Policy: Reproduced under a Creative Commons License