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Article

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

1
Research Department, Royal College of Surgeons in Ireland, Adliya 15503, Bahrain
2
Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull YO10 5DD, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Dawn Belt Davis and Raghavendra G. Mirmira
Metabolites 2022, 12(3), 196; https://doi.org/10.3390/metabo12030196
Received: 17 January 2022 / Revised: 29 January 2022 / Accepted: 12 February 2022 / Published: 22 February 2022
(This article belongs to the Special Issue The Role of β Cells in Diabetes)
Development of type-2 diabetes(T2D) is preceded by β-cell dysfunction and loss. However, 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. View Full-Text
Keywords: biomarkers; prognostic; diagnostic; type 2 diabetes; euglycemia; glucose variability biomarkers; prognostic; diagnostic; type 2 diabetes; euglycemia; glucose variability
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MDPI and ACS Style

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

AMA Style

Moin ASM, Sathyapalan T, Atkin SL, Butler AE. Diagnostic and Prognostic Protein Biomarkers of β-Cell Function in Type 2 Diabetes and Their Modulation with Glucose Normalization. Metabolites. 2022; 12(3):196. https://doi.org/10.3390/metabo12030196

Chicago/Turabian Style

Moin, Abu S.M., Thozhukat Sathyapalan, Stephen L. Atkin, and Alexandra E. Butler. 2022. "Diagnostic and Prognostic Protein Biomarkers of β-Cell Function in Type 2 Diabetes and Their Modulation with Glucose Normalization" Metabolites 12, no. 3: 196. https://doi.org/10.3390/metabo12030196

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