Proteomics profiling and association with cardiorenal complications in type 2 diabetes subtypes in Asian population
Diabetes Research and Clinical Practice, 2024
Gurung R., Zheng H., Lee B., Liu S., Liu J., Chan C., Ang K., Subramaniam T., Sum C., Coffman T., Lim S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases | Patient Stratification | Plasma | O Olink Explore 3072/384 |
Abstract
Aim
Among multi-ethnic Asians, type 2 diabetes (T2D) clustered in three subtypes; mild obesity-related diabetes (MOD), mild age-related diabetes with insulin insufficiency (MARD-II) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII) had differential cardio-renal complication risk. We assessed the proteomic profiles to identify subtype specific biomarkers and its association with diabetes complications.
Methods
1448 plasma proteins at baseline were measured and compared across the T2D subtypes. Multivariable cox regression was used to assess associations between significant proteomics features and cardio-renal complications.
Results
Among 645 T2D participants (SIRD-RII [19%], MOD [45%], MARD-II [36%]), 295 proteins expression differed significantly across the groups. These proteins were enriched in cell adhesion, neurogenesis and inflammatory response processes. In SIRD-RII group, ADH4, ACY1, THOP1, IGFBP2, NEFL, ENTPD2, CALB1, HAO1, CTSV, ITGAV, SCLY, EDA2R, ERBB2 proteins significantly associated with progressive CKD and LILRA5 protein with incident heart failure (HF). In MOD group, TAFA5, RSPO3, EDA2R proteins significantly associated with incident HF. In MARD-II group, FABP4 protein significantly associated with progressive CKD and PTPRN2 protein with major adverse cardiovascular events. Genetically determined NEFL and CALB1 were associated with kidney function decline.
Conclusions
Each T2D subtype has unique proteomics signature and association with clinical outcomes and underlying mechanisms.