Aim/Hypothesis: Five subgroups were described in European diabetes patients using a data driven machine learning approach on commonly measured variables. We aimed to test the applicability of this phenotyping in Indian young-onset type 2 diabetes patients. Methods: We applied the European derived centroids to the Indian type 2 diabetes patients diagnosed before 45 years of age from the WellGen (n = 1612) cohort. We also applied de novo k-means clustering to the WellGen cohort to validate the subgroups. We then compared clinical and metabolic-endocrine characteristics and the complication rates between the subgroups. We also compared characteristics of the WellGen subgroups with those of two young European cohorts ANDIS (n = 962) and DIREVA (n = 420). Subgroups were also assessed in two other Indian cohorts, Ahmedabad (n = 187) and PHENOEINDY-2 (n = 205). Results: Both Indian and European young type 2 diabetes patients were predominantly classified into severely insulin-deficient (SIDD) and mild obesity-related (MOD) subgroups, while the severely insulin-resistant (SIRD) and mild age-related (MARD) subgroups were rare. In WellGen, SIDD (53%) was more common than MOD (38%), contrary to figures in Europeans (Swedish: 26% vs 68%, Finnish: 24% vs 71% respectively). A higher proportion of SIDD compared to MOD was also seen in Ahmedabad (57% vs 33%) and in PHENOEINDY-2 (67% vs 23%). Both in Indians and Europeans, the SIDD subgroup was characterized by insulin deficiency and hyperglycemia, MOD by obesity, SIRD by severe insulin resistance and MARD by mild metabolic-endocrine disturbances. In WellGen, nephropathy and retinopathy were more prevalent in SIDD compared to MOD while the latter had higher prevalence of neuropathy. Conclusions/Interpretation: Our data identified insulin deficiency as the major driver of type 2 diabetes in young Indians, unlike in young European patients in whom obesity and insulin resistance predominate. Our results provide useful clues to pathophysiological mechanisms and susceptibility to complications in young Indian type 2 diabetes, and suggest a need to review management strategies.

中文翻译：

---

印度年轻的2型糖尿病亚组显示胰岛素缺乏是主要驱动因素

目的/假设：使用数据驱动的机器学习方法对常见的变量进行描述，在欧洲糖尿病患者中描述了五个亚组。我们旨在测试这种表型在印度年轻发病的2型糖尿病患者中的适用性。方法：我们将欧洲衍生的质心应用于来自WellGen（n = 1612）队列的在45岁之前诊断出的印度2型糖尿病患者。我们也应用了de novok均值聚类到WellGen队列以验证子组。然后，我们比较了亚组之间的临床和代谢-内分泌特征以及并发症发生率。我们还比较了WellGen子组的特征与两个欧洲年轻队列ANDIS（n = 962）和DIREVA（n = 420）的特征。在另外两个印度队列中，也对亚组进行了评估，其中艾哈迈达巴德（n = 187）和苯妥英钠-2（n = 205）。结果：印度和欧洲的年轻2型糖尿病患者主要分为严重胰岛素缺乏（SIDD）和轻度肥胖相关（MOD）亚组，而严重胰岛素抵抗（SIRD）和轻度年龄相关（MARD）亚组是稀有的。在WellGen中，SIDD（53％）比MOD（38％）更常见，与欧洲人相反（瑞典：26％比68％，芬兰：24％比71％）。在艾哈迈达巴德（57％比33％）和PHENOEINDY-2（67％比23％）中，与MOD相比，SIDD的比例也更高。在印度人和欧洲人中，SIDD亚组均以胰岛素缺乏和高血糖为特征，MOD以肥胖为特征，SIRD以严重胰岛素抵抗为特征，MARD以轻度代谢-内分泌紊乱为特征。在WellGen中， 结论/解释：我们的数据表明，胰岛素缺乏是年轻印度人2型糖尿病的主要驱动因素，与肥胖和胰岛素抵抗为主的欧洲年轻患者不同。我们的研究结果为年轻的印度2型糖尿病的病理生理机制和并发症易感性提供了有用的线索，并建议有必要审查治疗策略。