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

Prasad, Rashmi B LU ; Asplund, Olof LU ; Shukla, Sharvari R ; Wagh, Rucha ; Kunte, Pooja ; Bhat, Dattatrey ; Parikh, Malay ; Shah, Meet ; Phatak, Sanat and Käräjämäki, Annemari , et al. (2022) In Diabetologia 65(1). p.65-78
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,... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ANDIS, diabetes
in
Diabetologia
volume
65
issue
1
pages
65 - 78
publisher
Springer
external identifiers
  • scopus:85117707559
  • pmid:34689214
ISSN
1432-0428
DOI
10.1007/s00125-021-05543-y
language
English
LU publication?
yes
additional info
© 2021. The Author(s).
id
a5738c91-2003-4c0b-ad80-2ad2bb15d77e
date added to LUP
2021-11-05 12:27:21
date last changed
2024-06-15 19:51:15
@article{a5738c91-2003-4c0b-ad80-2ad2bb15d77e,
  abstract     = {{<p>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.</p><p>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).</p><p>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.</p><p>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.</p>}},
  author       = {{Prasad, Rashmi B and Asplund, Olof and Shukla, Sharvari R and Wagh, Rucha and Kunte, Pooja and Bhat, Dattatrey and Parikh, Malay and Shah, Meet and Phatak, Sanat and Käräjämäki, Annemari and Datta, Anupam and Kakati, Sanjeeb and Tuomi, Tiinamaija and Saboo, Banshi and Ahlqvist, Emma and Groop, Leif and Yajnik, Chittaranjan S}},
  issn         = {{1432-0428}},
  keywords     = {{ANDIS; diabetes}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{65--78}},
  publisher    = {{Springer}},
  series       = {{Diabetologia}},
  title        = {{Subgroups of patients with young-onset type 2 diabetes in India reveal insulin deficiency as a major driver}},
  url          = {{http://dx.doi.org/10.1007/s00125-021-05543-y}},
  doi          = {{10.1007/s00125-021-05543-y}},
  volume       = {{65}},
  year         = {{2022}},
}