National Institute for Health Research Global Health Unit for Diabetes Outcomes Research, Division of Population Health & Genomics, School of Medicine, University of Dundee, Dundee, UK.
Dr Mohan's Diabetes Specialities Centre and Madras Diabetes Research Foundation, Chennai, India.
Diabetologia. 2022 Jun;65(6):973-983. doi: 10.1007/s00125-022-05671-z. Epub 2022 Mar 5.
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.
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.
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.
目的/假设：与白种欧洲人相比，南亚人总体上、尤其是印度裔人患 2 型糖尿病的风险更高，发病年龄也更早。发病年龄更早与肥胖、β细胞功能和胰岛素敏感性的关系还没有得到充分的研究。
我们使用了两个印度裔人群队列，即印度医学研究委员会-印度糖尿病研究（ICMR-INDIAB 队列）和 Dr Mohan 的糖尿病专科中心（DMDSC 队列），以及一个白种欧洲人群队列，即东苏格兰糖尿病队列（ESDC）。采用横断面设计，我们根据 BMI 检查了年轻发病糖尿病患者中健康、超重和肥胖参与者的相对患病率。我们探讨了临床测量的β细胞功能在印度人发病中的作用。最后，还检查了由于β细胞功能不良导致糖尿病风险的分区多基因评分（pPS）的比较分布。使用英国生物库的数据寻找遗传发现的复制结果。
白种欧洲人中正常 BMI 的年轻发病糖尿病的患病率为 9.3%，而印度裔人中为 24-39%。在年轻发病糖尿病的印度裔人群中，在调整了 2 型糖尿病家族史、性别、胰岛素敏感性和高密度脂蛋白胆固醇后，与肥胖者相比，瘦者的刺激 C 肽低 492pmol/ml（IQR 353-616，p<0.0001）。我们研究中的印度裔人和英国生物库中的南亚裔人比白种欧洲人拥有更多的风险等位基因。对β细胞功能的 pPS 进行加权后，印度裔人的遗传决定的β细胞功能低于白种欧洲人（p<0.0001）。pPS 与印度裔人的诊断年龄有关，但与白种欧洲人无关。pPS 解释了印度裔人中正常 BMI 的临床测量β细胞功能的 2%、超重和肥胖 BMI 的 2%、1.2%、0.97%和 0.36%的变异。
结论/解释：与白种欧洲人相比，年轻发病糖尿病的瘦 BMI 患病率在印度裔中高出两倍多。这种瘦、年轻发病的糖尿病表型部分是由较低的β细胞功能驱动的。我们证明，患有糖尿病的印度人也具有较低的遗传决定的β细胞功能。
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