Care and Public Health Research Institute, University of Maastricht, Maastricht, The Netherlands.
Eur J Endocrinol. 2012 Feb;166(2):325-32. doi: 10.1530/EJE-11-0662. Epub 2011 Nov 29.
High-mobility group box-1 (HMGB1) is a pro-inflammatory cytokine that may contribute to the pathogenesis of micro- and macrovascular complications commonly observed in diabetes. We investigated whether HMGB1 is associated with: i) markers of low-grade inflammation (LGI) and endothelial dysfunction (ED) and pulse pressure (PP, a marker of arterial stiffness); ii) prevalent nephropathy, retinopathy and cardiovascular disease (CVD) in type 1 diabetes; and iii) the potential mediating roles of LGI, ED and PP therein.
This was a cross-sectional nested case-control study of 463 patients (226 women; mean age 40±10 years) with type 1 diabetes from the EURODIAB Prospective Complications Study. We used linear and binary or multinomial logistic regression analyses adjusted for traditional risk factors.
Serum Ln-HMGB1 levels were positively associated with LGI and ED (standardised β=0.07 (95% confidence interval (CI): 0.02-0.12) and β=0.08 (95% CI: 0.02-0.14) respectively), but not with PP. Higher Ln-HMGB1 (per unit) was associated with greater odds of micro- and macroalbuminuria: odds ratio (OR)=1.24 (95% CI: 0.90-1.71) and OR=1.61 (95% CI: 1.15-2.25) respectively, P for trend=0.004. Further adjustments for LGI or ED did not attenuate these associations. No such associations were found between Ln-HMGB1 and estimated glomerular filtration rate (eGFR), retinopathy or CVD, however.
In type 1 diabetes, higher serum HMGB1 levels are associated with greater prevalence and severity of albuminuria, though not with eGFR, retinopathy and CVD. Prospective studies are needed to clarify the causal role of HMGB1, if any, in the pathogenesis of vascular complications in type 1 diabetes.
高迁移率族蛋白 B1（HMGB1）是一种促炎细胞因子，可能与糖尿病中常见的微血管和大血管并发症的发病机制有关。我们研究了 HMGB1 是否与以下因素相关：i）低度炎症（LGI）和内皮功能障碍（ED）和脉压（PP，动脉僵硬度的标志物）标志物；ii）1 型糖尿病中的普遍肾病、视网膜病变和心血管疾病（CVD）；以及 iii）LGI、ED 和 PP 在此类疾病中的潜在介导作用。
这是一项横断面嵌套病例对照研究，纳入了来自 EURODIAB 前瞻性并发症研究的 463 例（226 例女性；平均年龄 40±10 岁）1 型糖尿病患者。我们使用线性和二项式或多项逻辑回归分析，调整了传统危险因素。
血清 Ln-HMGB1 水平与 LGI 和 ED 呈正相关（标准化β=0.07（95%置信区间（CI）：0.02-0.12）和β=0.08（95%CI：0.02-0.14）），但与 PP 无关。Ln-HMGB1 （单位）较高与微量白蛋白尿和大量白蛋白尿的几率较高相关：比值比（OR）=1.24（95%CI：0.90-1.71）和 OR=1.61（95%CI：1.15-2.25），趋势 P 值=0.004。进一步调整 LGI 或 ED 并不能减弱这些关联。然而，在 Ln-HMGB1 与估算肾小球滤过率（eGFR）、视网膜病变或 CVD 之间未发现这种关联。
在 1 型糖尿病中，较高的血清 HMGB1 水平与白蛋白尿的患病率和严重程度增加相关，但与 eGFR、视网膜病变和 CVD 无关。需要前瞻性研究来阐明 HMGB1 是否在 1 型糖尿病血管并发症的发病机制中具有因果作用。
