Projects per year
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. Graphical abstract: [Figure not available: see fulltext.]
|Number of pages||11|
|Early online date||5 Mar 2022|
|Publication status||Published - Jun 2022|
- Beta cell function
- Genetics of type 2 diabetes
- South Asian diabetes
- Young-onset diabetes
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
FingerprintDive into the research topics of 'Young onset diabetes in Asian Indians is associated with lower measured and genetically determined beta-cell function: an INSPIRED study'. Together they form a unique fingerprint.
- 2 Finished
Scotland India Diabetes Health Informatics Unit (joint with Madras Diabetes Research Foundation)
Doney, A., McCrimmon, R., Palmer, C., Pearson, E. & Trucco, M.
1/06/17 → 30/09/21
Stratified Medicine in Type 2 Diabetes: Insights from the Study of Drug Response (New Investigator Award)
16/02/15 → 15/08/21
- 9 Citations
- 1 Comment/debate
Correction to: Young-onset diabetes in Asian Indians is associated with lower measured and genetically determined beta cell function (Diabetologia, (2022), 65, 6, (973-983), 10.1007/s00125-022-05671-z)Siddiqui, M. K., 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. & Mohan, V., Jul 2022, In: Diabetologia. 65, 7, p. 1237 1 p.
Research output: Contribution to journal › Comment/debate › peer-reviewOpen Access