Journal Article Ppublish 1 citation
PubMed: 42473140 DOI: 10.1155/jdr/2756059
Expression Signatures of Vascular Complication-Associated Proteins in Type 2 Diabetes: A Multiomics Analysis From the FIELD Study.
J Diabetes Res 2026(1):e2756059
Authors: Habib Francis, Andrzej S Januszewski, Abubakar S Mangani, Matthew B O Rourke, Michael L H Huang, Fahmida K Ema, Anandwardhan A Hardikar, Mugdha V Joglekar, David R Sullivan, Ronald C W Ma, Sanjeev Galande, Val Gebski, Michael D Emden, R John Simes, Alicia J Jenkins, Mark P Molloy, Anthony C Keech
Affiliations
- NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia, sydney.edu.au.
- Sydney Pharmacy School, The University of Sydney, Sydney, Australia, sydney.edu.au.
- Bowel Cancer and Biomarker Research Laboratory, School of Medical Sciences, Kolling Institute, The University of Sydney, St Leonards, Australia, sydney.edu.au.
- Baker Heart and Diabetes Institute, Melbourne, Australia, baker.edu.au.
- Western Sydney University School of Medicine, Campbelltown, Australia.
- Royal Prince Alfred Hospital, Camperdown, Australia, nsw.gov.au.
- Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Sha Tin, Hong Kong, China, cuhk.edu.hk.
- Shiv Nadar Institution of Eminence, Gautam Buddha Nagar, Uttar Pradesh, India.
- Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
- NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia, sydney.edu.au. Baker Heart and Diabetes Institute, Melbourne, Australia, baker.edu.au.
Abstract
AIMS
The aim of the study is to integrate targeted transcriptomic analyses of previously identified biomarker proteins (proteomic findings) to better understand vascular complications (Cx) in Type 2 diabetes (T2D).
METHODS
Total RNA was extracted from baseline citrate plasma samples of 543 individuals with T2D from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. Among these, 224 participants had microvascular Cx, 142 had macrovascular Cx (51 had both types of Cx) and 228 had no Cx (control group). mRNA expression was quantified using the OpenArray platform and group differences were analysed using ΔΔct values. Neutrophil elastase (NE) protein levels were measured in baseline plasma by ELISA.
RESULTS
Eleven genes were retained for focused analysis. For microCx, the largest gene expression differences were observed for clusterin (~2-fold upregulation) and integrin alpha-IIb (~50% downregulation), compared with the control group. For macroCx, clusterin exhibited the strongest upregulation (~2.5-fold), whereas apolipoprotein F showed the greatest downregulation (~20%). Comparative analysis of proteomic and transcriptomic data across study groups revealed that only 32% of gene expression differences were mirrored at the protein level. NE levels were highest in the microCx group and were significantly elevated versus control only in that group; NE levels also correlated inversely with circulating actin protein expression (R 2 = 0.92).
CONCLUSION
Combining proteomic and targeted plasma transcriptomic data provides exploratory insights into biological processes associated with vascular complications in T2D and highlights NE as a candidate component of a proteolytic pathway for further investigation.
MeSH
Diabetes Mellitus, Up-Regulation, Genes, Clusterin, Leukocyte Elastase, Biomarkers, Down-Regulation, Plasma, Gene Expression, Diabetes Mellitus, Type 2