Type 2 diabetes classification: a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort

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  • Diana Hedevang Christensen
  • Sia K. Nicolaisen
  • Emma Ahlqvist
  • Jacob V. Stidsen
  • Jens Steen Nielsen
  • Kurt Hojlund
  • Michael H. Olsen
  • Sonia García-Calzón
  • Charlotte Ling
  • Rungby, Jørgen
  • Ivan Brandslund
  • Peter Vestergaard
  • Niels Jessen
  • Hansen, Torben
  • Charlotte Brøns
  • Henning Beck-Nielsen
  • Henrik T Sørensen
  • Reimar W. Thomsen
  • Vaag, Allan

Introduction A Swedish data-driven cluster study identified four distinct type 2 diabetes (T2D) clusters, based on age at diagnosis, body mass index (BMI), hemoglobin A1c (HbA1c) level, and homeostatic model assessment 2 (HOMA2) estimates of insulin resistance and beta-cell function. A Danish study proposed three T2D phenotypes (insulinopenic, hyperinsulinemic, and classical) based on HOMA2 measures only. We examined these two new T2D classifications using the Danish Centre for Strategic Research in Type 2 Diabetes cohort. Research design and methods In 3529 individuals, we first performed a k-means cluster analysis with a forced k-value of four to replicate the Swedish clusters: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild age-related (MARD), and mild obesity-related (MOD) diabetes. Next, we did an analysis open to alternative k-values (ie, data determined the optimal number of clusters). Finally, we compared the data-driven clusters with the three Danish phenotypes. Results Compared with the Swedish findings, the replicated Danish SIDD cluster included patients with lower mean HbA1c (86 mmol/mol vs 101 mmol/mol), and the Danish MOD cluster patients were less obese (mean BMI 32 kg/m 2 vs 36 kg/m 2). Our data-driven alternative k-value analysis suggested the optimal number of T2D clusters in our data to be three, rather than four. When comparing the four replicated Swedish clusters with the three proposed Danish phenotypes, 81%, 79%, and 69% of the SIDD, MOD, and MARD patients, respectively, fitted the classical T2D phenotype, whereas 70% of SIRD patients fitted the hyperinsulinemic phenotype. Among the three alternative data-driven clusters, 60% of patients in the most insulin-resistant cluster constituted 76% of patients with a hyperinsulinemic phenotype. Conclusion Different HOMA2-based approaches did not classify patients with T2D in a consistent manner. The T2D classes characterized by high insulin resistance/hyperinsulinemia appeared most distinct.

OriginalsprogEngelsk
Artikelnummere002731
TidsskriftB M J Open Diabetes Research & Care
Vol/bind10
Udgave nummer2
Antal sider12
ISSN2052-4897
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Competing interests The Department of Clinical Epidemiology, Aarhus University Hospital, receives funding for other studies from companies in the form of institutional research grants to (and administered by) Aarhus University. None of these studies has any relation to the present study. JVS, KH, MHO, PV, NJ, CB, and AV are all affiliated with Danish Steno Diabetes centers. The Steno Diabetes centers are funded by the Novo Nordisk Foundation. EA was funded by grants from the Swedish Research Council (2017-02688, 2020-02191) and the Novo Nordisk foundation (NNF18OC0034408).

Funding Information:
Funding The DD2 study was supported by the Danish Agency for Science (grant numbers 09-067009 and 09-075724), The Danish Health and Medicines Authority, The Danish Diabetes Association, Region of Southern Denmark, and the Novo Nordisk Foundation (grant numbers NNF17SA0030962-2 and NNF20O0063292). The DD2 biobank was supported by an unrestricted donation from Novo Nordisk A/S. Project partners are listed on the website www.DD2.nu.

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