Abstract
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.
Highlights
The chronic hyperglycemia of type 2 diabetes (T2D) results from a combination of progressive pancreatic islet β-cell loss or failure coupled with increased insulin resistance (IR) in key peripheral tissues—namely, liver, skeletal muscle and adipose tissue [1,2,3]
These included Adiponectin, Endocan and KIT, which were lower in T2D, whilst other markers—namely, Cathepsin-D, Cadherin-E, Kallikrein-4, Aminoacylase-1, Insulin-like growth factor-binding protein-4 (IGFBP4) and Reticulon-4 receptor (RTN4R)—were higher in T2D
This suggests that, with the onset of T2D, there is a decrease in the discrimination of these biomarker proteins, with 34 proteins no longer being discriminatory; 9 proteins remained different to controls that may be of importance in terms of clinical application
Summary
The chronic hyperglycemia of type 2 diabetes (T2D) results from a combination of progressive pancreatic islet β-cell loss or failure coupled with increased insulin resistance (IR) in key peripheral tissues—namely, liver, skeletal muscle and adipose tissue [1,2,3]. Novel prognostic and diagnostic biomarkers have been suggested following a study of aptamer based proteomics, together with measurement of microRNA, in subjects with impaired glucose tolerance (IGT); plasma analytics were compared in the group where IGT declined over time versus an IGT group where the markers remained stable over the 3-year follow-up period [15]. This study was undertaken using the same aptamer based proteomic platform of this study [15] to determine if these recognized prognostic and diagnostic markers had utility in established T2D. This prospective case-controlled study included subjects with T2D (n = 23) and nondiabetic control (n = 23) Caucasian subjects, all aged 40–70 years. None of the patients with T2D enrolled in this study had any evidence of microvascular or macrovascular diabetes-related complications. (Table 1)
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