Diagnostic and Prognostic Protein Biomarkers of β-Cell Function in Type 2 Diabetes and Their Modulation with Glucose Normalization

Moin, Abu Saleh Md; Sathyapalan, Thozhukat; Atkin, Stephen L.; Butler, Alexandra E.

Abstract

Development of type-2 diabetes(T2D) is preceded by β-cell dysfunction and loss. How-ever, accurate measurement of β-cell function remains elusive. Biomarkers have been reported to predict β-cell functional decline but require validation. Therefore, we determined whether reported protein biomarkers could distinguish patients with T2D (onset < 10-years) from controls. A prospective, parallel study in T2D (n = 23) and controls (n = 23) was undertaken. In T2D subjects, insulin-induced blood glucose normalization from baseline 7.6 ± 0.4 mmol/L (136.8 ± 7.2 mg/dL) to 4.5 ± 0.07 mmol/L (81 ± 1.2 mg/dL) was maintained for 1-h. Controls were maintained at 4.9 ± 0.1 mmol/L (88.2 ± 1.8 mg/dL). Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement determined a 43-protein panel reported as diagnostic and/or prognostic for T2D. At baseline, 9 proteins were altered in T2D. Three of 13 prognostic/diagnostic proteins were lower in T2D: Adiponectin (p < 0.0001), Endocan (p < 0.05) and Mast/stem cell growth factor receptor-Kit (KIT) (p < 0.01). Two of 14 prognostic proteins [Cathepsin-D (p < 0.05) and Cadherin-E (p < 0.005)], and four of 16 diagnostic proteins [Kallikrein-4 (p = 0.001), Aminoacylase-1 (p = 0.001), Insulin-like growth factor-binding protein-4 (IGFBP4) (p < 0.05) and Reticulon-4 receptor (RTN4R) (p < 0.001)] were higher in T2D. Protein levels were unchanged following glucose normalization in T2D. Our results suggest that a focused biomarker panel may be useful for assessing β-cell dysfunction and may complement clinical decision-making on insulin therapy. Unchanged post-glucose normalization levels indicate these are not acute-phase proteins or affected by glucose variability.

Citation

Moin, A. S. M., Sathyapalan, T., Atkin, S. L., & Butler, A. E. (2022). Diagnostic and Prognostic Protein Biomarkers of β-Cell Function in Type 2 Diabetes and Their Modulation with Glucose Normalization. Metabolites, 12(3), Article 196. https://doi.org/10.3390/metabo12030196

• Journal Article Type: Article
• Acceptance Date: Feb 12, 2022
• Online Publication Date: Feb 22, 2022
• Publication Date: 2022-03
• Deposit Date: Mar 28, 2022
• Publicly Available Date: Mar 29, 2022
• Journal: Metabolites
• Electronic ISSN: 2218-1989
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 3
• Article Number: 196
• DOI: https://doi.org/10.3390/metabo12030196
• Keywords: Biomarkers; Prognostic; Diagnostic; Type 2 diabetes; Euglycemia; Glucose variability
• Public URL: https://hull-repository.worktribe.com/output/3946354