Identifying blood biomarkers for type 2 diabetes subtyping: a report from the ORIGIN trial

Marie Pigeyre, Hertzel Gerstein, Emma Ahlqvist, Sibylle Hess, Guillaume Paré

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/hypothesis: Individuals with diabetes can be clustered into five subtypes using up to six routinely measured clinical variables. We hypothesised that circulating protein levels might be used to distinguish between these subtypes. We recently used five of these six variables to categorise 7017 participants from the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial into these subtypes: severe autoimmune diabetes (SAID, n=241), severe insulin-deficient diabetes (SIDD, n=1594), severe insulin-resistant diabetes (SIRD, n=914), mild obesity-related diabetes (MOD, n=1595) and mild age-related diabetes (MARD, n=2673). Methods: Forward-selection logistic regression models were used to identify a subset of 233 cardiometabolic protein biomarkers that were independent determinants of one subtype vs the others. We then assessed the performance of adding identified biomarkers (one after one, from the most discriminant to the least) to predict each subtype vs the others using area under the receiver operating characteristic curve (AUC ROC). Models were adjusted for age, sex, ethnicity, C-peptide level, diabetes duration and glucose-lowering medication usage at blood collection. Results: A total of 25 biomarkers were independent determinants of subtypes, including 13 for SIDD, 2 for SIRD, 7 for MOD and 11 for MARD (all p<4.3 × 10−5). The performance of the biomarker sets (comprising 1 to 25 biomarkers), assessed through the AUC ROC, ranged from 0.611 to 0.734, 0.723 to 0.861, 0.672 to 0.742, and 0.651 to 0.751, for SIDD, SIRD, MOD and MARD, respectively. No biomarkers other than GAD antibodies were determinants of SAID. Conclusions/interpretation: We identified 25 serum biomarkers, as independent determinants of type 2 diabetes subtypes, that could be combined into a diagnostic test for subtyping. Trial registration: ORIGIN trial, ClinicalTrials.gov NCT00069784. Graphical abstract: [Figure not available: see fulltext.].

Original languageEnglish
Pages (from-to)1045-1051
JournalDiabetologia
Volume66
Issue number6
Early online date2023
DOIs
Publication statusPublished - 2023

Subject classification (UKÄ)

  • Endocrinology and Diabetes

Free keywords

  • Blood biomarkers
  • Circulating biomarkers
  • Diabetes clusters
  • Diabetes subtypes
  • ORIGIN
  • Type 2 diabetes

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