Villafan-Bernal José Rafael, Barajas-Olmos Francisco, Guzmán-Guzmán Iris Paola, Martínez-Hernández Angélica, Contreras-Cubas Cecilia, García-Ortiz Humberto, Morales-Rivera Monserrat I, Martínez-Portilla Raigam Jafet, Orozco Lorena
Immunogenomics and Metabolic Diseases Laboratory, Instituto Nacional de Medicina Genómica, SS, Mexico City 14610, Mexico.
Investigador por México, Consejo Nacional de Humanidades Ciencia y Tecnología (CONAHCYT), Mexico City 03940, Mexico.
Antioxidants (Basel). 2024 Dec 19;13(12):1564. doi: 10.3390/antiox13121564.
Endoplasmic reticulum stress (ERS) is activated in all cells by stressors such as hyperglycemia. However, it remains unclear which specific serum biomarkers of ERS are consistently altered in type 2 diabetes (T2D). We aimed to identify serum ERS biomarkers that are consistently altered in T2D and its complications, and their correlation with metabolic and anthropometric variables. We performed a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analyses and Systematic Reviews of Observational Studies (MOOSE). The risk of bias was assessed using the Newcastle-Ottawa scale. Random-effects models weighted by the inverse variance were employed to estimate the standardized mean difference and correlations as effect size measures. Indicators of heterogeneity and meta-regressions were evaluated. Of the 1206 identified studies, 22 were finally included, representing 11,953 subjects (2224 with T2D and 9992 non-diabetic controls). Most studies were of high quality. Compared with controls, subjects with T2D had higher circulating levels of heat shock protein 70 (HSP70; SMD: 2.30, 95% CI 1.13-3.46; < 0.001) and secretagogin (SMD: 0.60, 95%CI 0.19-1.01; < 0.001). They also had higher serum levels of peroxiredoxin-1, -2, -4, and -6. Secretagogin inversely correlated with HOMA-IR, yet positively correlated with HOMA-B, HbA1c, and FPG. PRX4 negatively correlated with HbA1c and FPG, while HSP70 positively correlated with HbA1c. In conclusion, six ERS biomarkers are consistently elevated in human T2D and correlate with glycemic control, insulin resistance, and β-cell function. Emerging evidence links serum ERS biomarkers to diabetes complications, but further research should evaluate their prognostic implications.
内质网应激（ERS）在所有细胞中都会因高血糖等应激源而被激活。然而，目前尚不清楚在2型糖尿病（T2D）中，哪些ERS的特定血清生物标志物会持续发生改变。我们旨在确定在T2D及其并发症中持续改变的血清ERS生物标志物，以及它们与代谢和人体测量学变量的相关性。我们按照系统评价和Meta分析的首选报告项目（PRISMA）以及观察性研究的Meta分析和系统评价（MOOSE）进行了系统评价和Meta分析。使用纽卡斯尔-渥太华量表评估偏倚风险。采用逆方差加权的随机效应模型来估计标准化平均差和相关性作为效应量指标。评估了异质性指标和Meta回归。在1206项已识别的研究中，最终纳入了22项，代表11953名受试者（2224名T2D患者和9992名非糖尿病对照）。大多数研究质量较高。与对照组相比，T2D患者的热休克蛋白70（HSP70；标准化平均差：2.30，95%置信区间1.13 - 3.46；P < 0.001）和分泌粒蛋白（标准化平均差：0.60，95%置信区间0.19 - 1.01；P < 0.001）的循环水平更高。他们的血清过氧化物还原酶-1、-2、-4和-6水平也更高。分泌粒蛋白与胰岛素抵抗指数（HOMA-IR）呈负相关，但与胰岛素分泌指数（HOMA-B）、糖化血红蛋白（HbA1c）和空腹血糖（FPG）呈正相关。过氧化物还原酶4（PRX4）与HbA1c和FPG呈负相关，而HSP70与HbA1c呈正相关。总之，六种ERS生物标志物在人类T2D中持续升高，并与血糖控制、胰岛素抵抗和β细胞功能相关。新出现的证据将血清ERS生物标志物与糖尿病并发症联系起来，但进一步的研究应评估它们的预后意义。
