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分泌型卷曲相关蛋白 4 在糖尿病前期和 2 型糖尿病中的作用:一项横断面研究。

Role of secreted frizzled-related protein 4 in prediabetes and type 2 diabetes: a cross sectional study.

机构信息

Research Division, Hospital Juárez de México, Av Instituto Politécnico Nacional 5160, Magdalena de las Salinas, Gustavo A. Madero, Mexico City, 07760, México.

出版信息

BMC Endocr Disord. 2024 Jun 4;24(1):78. doi: 10.1186/s12902-024-01613-5.

Abstract

BACKGROUND

Type 2 diabetes (T2D) has become an epidemic. Delays in diagnosis and as a consequent late treatment has resulted in high prevalence of complications and mortality. Secreted frizzled-related protein 4 (SFRP4), has been recently identified as a potential early biomarker of T2D related to obesity, due to its association with low grade inflammation in adipose tissue and impaired glucose metabolism. We aimed to evaluate the role of SFRP4 in prediabetes and T2D in a Mexican population.

METHODS

This was a cross-sectional study that included 80 subjects with T2D, 50 subjects with prediabetes and 50 healthy individuals. Fasting SFRP4 and insulin concentrations were measured by ELISA. Human serum IL-10, IL-6, IL-1β and IL-8 levels were quantified by flow cytometry. Genotyping was performed by TaqMan® probes.

RESULTS

Prediabetes and T2D patients had significantly higher SFRP4 levels than controls (P < 0.05). In turn, prediabetes subjects had higher SFRP4 concentrations than control subjects (P < 0.05). Additionally, the prediabetes and T2D groups had higher concentrations of proinflammatory molecules such as IL-6, IL-1β and IL-8, and lower concentrations of IL-10, an anti-inflammatory cytokine, than controls (P < 0.001). The serum SFRP4 concentrations were positively correlated with parameters that are elevated in prediabetes and T2D states, such as, HbA1c and homeostasis model assessment insulin resistance (HOMA-IR), (r = 0.168 and 0.248, respectively, P < 0.05). Also, serum SFRP4 concentrations were positively correlated with concentrations of pro-inflammatory molecules (CRP, IL-6, IL-1β and IL-8) and negatively correlated with the anti-inflammatory molecule IL-10, even after adjusting for body mass index and age (P < 0.001). The genetic variant rs4720265 was correlated with low HDL concentrations in T2D (P < 0.05).

CONCLUSIONS

SFRP4 correlates positively with the stage of prediabetes, suggesting that it may be an early biomarker to predict the risk of developing diabetes in people with high serum concentrations of SFRP4, although further longitudinal studies are required.

摘要

背景

2 型糖尿病(T2D)已成为一种流行病。诊断和治疗的延迟导致并发症和死亡率的高发。分泌卷曲相关蛋白 4(SFRP4)最近被确定为与肥胖相关的 T2D 的潜在早期生物标志物,因为它与脂肪组织中的低度炎症和葡萄糖代谢受损有关。我们旨在评估 SFRP4 在墨西哥人群中对前驱糖尿病和 T2D 的作用。

方法

这是一项横断面研究,包括 80 例 T2D 患者、50 例前驱糖尿病患者和 50 例健康对照者。通过 ELISA 法测定空腹 SFRP4 和胰岛素浓度。通过流式细胞术定量测定人血清 IL-10、IL-6、IL-1β 和 IL-8 水平。采用 TaqMan®探针进行基因分型。

结果

前驱糖尿病和 T2D 患者的 SFRP4 水平明显高于对照组(P<0.05)。相反,前驱糖尿病患者的 SFRP4 浓度高于对照组(P<0.05)。此外,前驱糖尿病和 T2D 组的促炎分子(如 IL-6、IL-1β 和 IL-8)浓度较高,抗炎细胞因子 IL-10 浓度较低,与对照组相比差异有统计学意义(P<0.001)。血清 SFRP4 浓度与前驱糖尿病和 T2D 状态下升高的参数呈正相关,如糖化血红蛋白(HbA1c)和稳态模型评估胰岛素抵抗(HOMA-IR)(r=0.168 和 0.248,分别,P<0.05)。此外,血清 SFRP4 浓度与促炎分子(CRP、IL-6、IL-1β 和 IL-8)浓度呈正相关,与抗炎分子 IL-10 浓度呈负相关,即使在调整体重指数和年龄后也是如此(P<0.001)。遗传变异 rs4720265 与 T2D 患者的低 HDL 浓度相关(P<0.05)。

结论

SFRP4 与前驱糖尿病阶段呈正相关,表明它可能是预测血清 SFRP4 浓度较高人群发生糖尿病风险的早期生物标志物,尽管需要进一步的纵向研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3868/11149217/da6d9a12bc65/12902_2024_1613_Fig1_HTML.jpg

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