RT Journal Article
SR Electronic
T1 Type 2 diabetes classification: a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort
JF BMJ Open Diabetes Research & Care
JO BMJ Open Diab Res Care
FD American Diabetes Association
SP e002731
DO 10.1136/bmjdrc-2021-002731
VO 10
IS 2
A1 Diana Hedevang Christensen
A1 Sia K Nicolaisen
A1 Emma Ahlqvist
A1 Jacob V Stidsen
A1 Jens Steen Nielsen
A1 Kurt Hojlund
A1 Michael H Olsen
A1 Sonia García-Calzón
A1 Charlotte Ling
A1 Jørgen Rungby
A1 Ivan Brandslund
A1 Peter Vestergaard
A1 Niels Jessen
A1 Torben Hansen
A1 Charlotte Brøns
A1 Henning Beck-Nielsen
A1 Henrik T Sørensen
A1 Reimar W Thomsen
A1 Allan Vaag
YR 2022
UL http://drc.bmj.com/content/10/2/e002731.abstract
AB 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/m2 vs 36 kg/m2). 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.Data may be obtained from a third party and are not publicly available. More information about the DD2 cohort can be found at the DD2 website: www.dd2.nu. The DD2 project has a Steering Group that strongly encourages national and international collaboration. Interested researchers can contact Professor Kurt Højlund at Kurt.Hoejlund@rsyd.dk. According to Danish data protection legislation, linked individual-level register data analyzed in the study cannot be shared or made publicly available. Register data are stored at the Danish Health Data Authority and can be made available for research on reasonable request and with permission from the Danish Data Protection Agency.