A study has proved that it is possible to identify clinically relevant subtypes of type 2 diabetes at the time of diagnosis in a Catalan population, with implications for its application in precision personalized medicine strategies.
“The results, published in the journal Cardiovascular Diabetology, open the door to a more precise classification of the disease that could help personalize patient monitoring and treatment from the earliest stages,” said the study coordinator, Dr. Dídac Mauricio, Scientific Director of the Diabetes and Metabolic Diseases Area of the CIBER (CIBERDEM) and Head of the Endocrinology, Diabetes, and Nutrition Research Group at the Sant Pau Research Institute (IR Sant Pau).
The study included 991 individuals with newly diagnosed type 2 diabetes, recruited between 2022 and 2026 from 28 centers in Barcelona and Lleida as part of the prospective COPERNICAN study. Using a statistical clustering method based on six clinical variables—age at diagnosis, glycated hemoglobin, body mass index, pancreatic beta-cell function, insulin resistance, and the presence of islet autoantibodies—the research team reproduced the classification model proposed by the Swedish group led by Dr. Emma Ahlqvist, which distinguishes five subtypes of type 2 diabetes.
The findings confirmed the existence of the phenotypes previously described in Scandinavian populations: severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). However, the study found that this classification of the latter four groups showed limited statistical stability in the Mediterranean population, as none of the groups reached the predefined stability threshold.
When the analysis was allowed to freely determine the optimal number of groups, researchers observed that, in addition to the autoimmune diabetes group, a solution with three additional clusters (subgroups) showed substantially greater stability: a phenotype characterized by obesity and insulin resistance, a phenotype characterized by insulin deficiency, and an age-related phenotype. “These results suggest that the metabolic heterogeneity of type 2 diabetes in our population may be better represented by a four-group structure, which has important implications for how we evaluate and classify patients from the time of diagnosis,” explained Dr. Mauricio.
The study also found that the obesity-related diabetes subgroup (MOD) did not show clear separation within this cohort but was instead distributed across the other groups. This suggests that, in the Mediterranean population, this phenotype may represent an intermediate metabolic spectrum rather than a distinct entity.
Because the classification was performed at the time of diagnosis, before the initiation of any treatment, the COPERNICAN cohort provides an opportunity to examine whether these metabolic subtypes exhibit different cardiovascular risk profiles over time. “Early identification of these phenotypes could allow us to better stratify this risk and guide preventive interventions in a more individualized manner,” added Dr. Berta Fernández-Camins, first author of the article and researcher at the University of Barcelona and IR Sant Pau.
The study included contributions from the group led by Dr. Àlex Perera from the Bioengineering, Biomaterials, and Nanomedicine Area of CIBER (CIBER-BBN), who is also a researcher at the Polytechnic University of Catalonia. Researchers from IDIAP Jordi Gol, the University of Lleida, and IRBLleida, among other institutions, also participated.
“This is the first study specifically designed to evaluate Ahlqvist’s phenotypic classification in a newly diagnosed Mediterranean cohort, unlike most replication studies, which have used pre-existing cohorts. Longitudinal follow-up of participants will make it possible to analyze the future evolution of each subgroup, their response to treatment, and the development of complications,” the research team concluded.
Fernandez-Camins B, Vlacho B, Rojo-López MI, Granado-Casas M, Gratacòs M, Ortega-Bravo M, Cendros-Massioui M, Palmieri F, Perera-LLuna A, Franch-Nadal J, Mauricio D. Phenotypic Clustering of Newly Diagnosed Type 2 Diabetes in a Mediterranean Cohort. Cardiovasc Diabetol. 2026. https://doi.org/10.1186/s12933-026-03198-w
