Moin Abu Saleh Md, Sathyapalan Thozhukat, Atkin Stephen L, Butler Alexandra E
Research Department, Royal College of Surgeons in Ireland, Adliya 15503, Bahrain.
Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull YO10 5DD, UK.
Metabolites. 2022 Feb 22;12(3):196. doi: 10.3390/metabo12030196.
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.
2型糖尿病（T2D）的发生之前会出现β细胞功能障碍和损失。然而，β细胞功能的准确测量仍然难以实现。据报道，生物标志物可预测β细胞功能下降，但需要进行验证。因此，我们确定所报道的蛋白质生物标志物是否能够区分T2D患者（发病时间<10年）和对照组。对T2D患者（n = 23）和对照组（n = 23）进行了一项前瞻性平行研究。在T2D受试者中，胰岛素诱导的血糖从基线的7.6±0.4 mmol/L（136.8±7.2 mg/dL）正常化至4.5±0.07 mmol/L（81±1.2 mg/dL）并维持1小时。对照组维持在4.9±0.1 mmol/L（88.2±1.8 mg/dL）。慢解离速率修饰适体（SOMA）-扫描血浆蛋白测量确定了一个43种蛋白质的组合，据报道对T2D具有诊断和/或预后价值。在基线时，T2D中有9种蛋白质发生了改变。13种预后/诊断蛋白质中有3种在T2D中较低：脂联素（p < 0.0001）、内皮糖蛋白（p < 0.05）和肥大/干细胞生长因子受体-Kit（KIT）（p < 0.01）。14种预后蛋白质中有2种[组织蛋白酶-D（p < 0.05）和钙黏蛋白-E（p < 0.005）]，以及16种诊断蛋白质中有4种[激肽释放酶-4（p = 0.001）、氨基酰化酶-1（p = 0.001）、胰岛素样生长因子结合蛋白-4（IGFBP4）（p < 0.05）和网织蛋白-4受体（RTN4R）（p < 0.001）]在T2D中较高。T2D患者血糖正常化后蛋白质水平未发生变化。我们的结果表明，一个有针对性的生物标志物组合可能有助于评估β细胞功能障碍，并可能补充胰岛素治疗的临床决策。血糖正常化后水平未发生变化表明这些不是急性期蛋白或不受血糖变异性的影响。
