Subgroups of patients with young-onset type 2 diabetes in India reveal insulin deficiency as a major driver,Diabetologia

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Subgroups of patients with young-onset type 2 diabetes in India reveal insulin deficiency as a major driver
Diabetologia ( IF 8.4 ) Pub Date : 2021-10-23 , DOI: 10.1007/s00125-021-05543-y
Rashmi B Prasad ₁ , Olof Asplund ₁ , Sharvari R Shukla _{2,

3} , Rucha Wagh ₂ , Pooja Kunte ₂ , Dattatrey Bhat ₂ , Malay Parekh ₄ , Meet Shah ₄ , Sanat Phatak ₂ , Annemari Käräjämäki _{5,

6} , Anupam Datta ₇ , Sanjeeb Kakati ₇ , Tiinamaija Tuomi _{1,

8,

9,

10} , Banshi Saboo ₄ , Emma Ahlqvist ₁ , Leif Groop _{1,

10} , Chittaranjan S Yajnik ₂

Affiliation

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 individuals with young-onset type 2 diabetes.

Methods

We applied the European-derived centroids to Indian individuals with type 2 diabetes diagnosed before 45 years of age from the WellGen cohort (n = 1612). 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-onset type 2 diabetes patients were predominantly classified into severe insulin-deficient (SIDD) and mild obesity-related (MOD) subgroups, while the severe insulin-resistant (SIRD) and mild age-related (MARD) subgroups were rare. In WellGen, SIDD (53%) was more common than MOD (38%), contrary to findings in Europeans (Swedish 26% vs 68%, Finnish 24% vs 71%, respectively). A higher proportion of SIDD compared with 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 characterised by insulin deficiency and hyperglycaemia, 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 with 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 individuals in whom obesity and insulin resistance predominate. Our results provide useful clues to pathophysiological mechanisms and susceptibility to complications in type 2 diabetes in the young Indian population and suggest a need to review management strategies.

Graphical abstract

中文翻译：

印度早发型 2 型糖尿病患者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用测量变量描述了欧洲糖尿病患者的五个亚组。我们的目的是测试这种表型在患有早发 2 型糖尿病的印度个体中的适用性。

方法

我们将源于欧洲的质心应用于 WellGen 队列中 45 岁之前诊断出的 2 型糖尿病印度个体 ( n = 1612)。我们还将 de novo k均值聚类应用于 WellGen 队列来验证子组。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。我们还将 WellGen 亚组的特征与两个年轻的欧洲队列 ANDIS ( n = 962) 和 DIREVA ( n = 420) 的特征进行了比较。还对另外两个印度队列 Ahmedabad ( n = 187) 和 PHENOEINDY-2 ( n = 205) 进行了亚组评估。

结果

印度和欧洲的年轻发病 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) 亚组是罕见的。在 WellGen 中，SIDD (53%) 比 MOD (38%) 更常见，这与欧洲人的研究结果相反（瑞典人分别为 26% 和 68%，芬兰人分别为 24% 和 71%）。在艾哈迈达巴德（57% vs 33%）和 PHENOEINDY-2（67% vs 23%），SIDD 的比例也高于 MOD。在印度人和欧洲人中，SIDD 亚组的特点是胰岛素缺乏和高血糖，MOD 是肥胖，SIRD 是严重胰岛素抵抗，MARD 是轻度代谢内分泌紊乱。在 WellGen 中，与 MOD 相比，SIDD 中肾病和视网膜病变的发生率更高，而后者的神经病变发生率更高。