Diabetes Zentrum, Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Ludwig-Maximilians-Universität, Ziemssenstrasse 1, 80336 München, Germany.
Eur J Endocrinol. 2012 Dec;167(6):847-53. doi: 10.1530/EJE-12-0472. Epub 2012 Sep 20.
Metabolic alterations and endothelial dysfunction are interrelated processes in type 2 diabetes (T2D) and metabolic syndrome (MetS) that often develop in parallel. We assessed the association of vasoactive precursor peptides (VPPs) with MetS and T2D.
Plasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and midregional pro-adrenomedullin (MR-proADM) were measured by novel sensitive assays in 1590 participants of the population-based KORA F4 study. The association of the VPPs with T2D, MetS defined by IDF criteria, the components of MetS, and insulin resistance (IR) was assessed in logistic regression models.
Elevated levels of CT-proET-1 and MR-proADM were associated with T2D, MetS, and IR in age- and sex-adjusted models. After adjustment for age, sex, former vascular complications, lifestyle factors, high-sensitive C-reactive protein, and serum creatinine, significant associations with MetS were found for MR-proADM (OR=5.94, 95% CI 3.78-9.33) and CT-proET-1 (OR=5.18, 95% CI 3.48-7.71) (top quartile vs bottom quartile). CT-proET-1 and MR-proADM were strongly associated with all components of MetS as defined by IDF criteria. After multivariable adjustment, association of CT-proET-1 and MR-proADM with pathological glucose tolerance and T2D disappeared and a borderline association with IR was found only for CT-proET-1 (OR=1.34, 95% CI 0.96-1.87).
We here demonstrate for the first time that plasma levels of both MR-proADM and CT-proET-1 levels are related to MetS and its components, thus suggesting that they possibly have a role as a surrogate biomarker for the disease and its complications.
代谢改变和内皮功能障碍是 2 型糖尿病(T2D)和代谢综合征(MetS)中相互关联的过程,它们通常同时发生。我们评估了血管活性前体肽(VPPs)与 MetS 和 T2D 的关系。
在基于人群的 KORA F4 研究的 1590 名参与者中,通过新的敏感测定法测量了 C 端前内皮素-1(CT-proET-1)和中区域前肾上腺髓质素(MR-proADM)的血浆水平。在逻辑回归模型中评估了 VPPs 与 T2D、IDF 标准定义的 MetS、MetS 的组成部分和胰岛素抵抗(IR)的关系。
在年龄和性别调整模型中,CT-proET-1 和 MR-proADM 水平升高与 T2D、MetS 和 IR 相关。在调整年龄、性别、既往血管并发症、生活方式因素、高敏 C 反应蛋白和血清肌酐后,MR-proADM(OR=5.94,95%CI 3.78-9.33)和 CT-proET-1(OR=5.18,95%CI 3.48-7.71)(最高四分位数与最低四分位数)与 MetS 有显著相关性。CT-proET-1 和 MR-proADM 与 IDF 标准定义的 MetS 的所有组成部分均密切相关。在多变量调整后,CT-proET-1 和 MR-proADM 与病理性葡萄糖耐量和 T2D 的相关性消失,仅与 CT-proET-1 呈边缘相关性(OR=1.34,95%CI 0.96-1.87)。
我们首次证明,MR-proADM 和 CT-proET-1 的血浆水平均与 MetS 及其组成部分有关,因此表明它们可能作为该疾病及其并发症的替代生物标志物发挥作用。