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

Abstract

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.

Keywords: Europe; India; Insulin deficiency; Subgroups; Type 2 diabetes; Young-onset type 2 diabetes.

Fig. 1

Distribution of participants from the WellGen and ANDIS study in the predefined clusters. (a–c) Distribution of WellGen participants, showing all participants (n=1612) (a), men with diabetes (n=902) (b) and women with diabetes (n=710) (c). (d–f) Distribution of ANDIS participants, showing all participants (n=962) (d), men with diabetes (n=567) (e) and women with diabetes (n=395) (f)

Fig. 2

Box plot of cluster characteristics in the WellGen and ANDIS studies. Distribution of age at diagnosis (a, f), BMI (b, g), HbA_1c (c, h), HOMA2-B (d, i) and HOMA2-IR (e, j) in the WellGen (a–e) and ANDIS (f–j) studies for each cluster. The central line within each box represents the median and the upper and lower limits of the box represent the IQR. The whiskers are the most extreme values within 1.5× the IQR from the first and second quartiles. k-means clustering was done separately for men and women; data are shown for each sex separately. F, female sex; M, male sex