Serum high mobility group box-1 and osteoprotegerin levels are associated with peripheral arterial disease and critical limb ischemia in type 2 diabetic subjects

血清高迁移率族蛋白 B1 和骨保护素水平与 2 型糖尿病患者的外周动脉疾病和严重肢体缺血有关

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作者:Silvia Giovannini, Giovanni Tinelli, Federico Biscetti, Giuseppe Straface, Flavia Angelini, Dario Pitocco, Luciana Mucci, Raffaele Landolfi, Andrea Flex

Background

High mobility group box-1 (HMGB-1) is a nuclear protein also acting as inflammatory mediator, whilst osteoprotegerin (OPG), member of tumor necrosis factor receptor superfamily, is indicated as marker of vascular calcification. Peripheral artery disease (PAD) and type 2 diabetes (T2D) are clinical conditions characterized by elevated serum inflammatory markers and vascular calcification enhancement. The

Conclusions

In T2D patients HMGB-1 and OPG serum levels are higher in patients affected by PAD and independently associated with its occurrence and clinical severity.

Methods

In this retrospective observational study, we have analyzed HMGB-1, OPG and inflammatory cytokines serum levels in 1393 type 2 diabetic patients with PAD and without PAD (WPAD).

Results

HMGB-1 (7.89 ± 15.23 ng/mL), OPG (6.54 ± 7.76 pmol/L), HsCRP (15.6 ± 14.4 mg/L) and IL-6 (56.1 ± 28.6 pg/mL) serum levels were significantly higher in patients with PAD than in those WPAD (3.02 ± 8.12 ng/mL, P ˂ 0.001; 2.98 ± 2.01 pmol/L, P < 0.001; 7.05 ± 4.4 mg/L, P < 0.001; 37.5 ± 20.2 pg/mL, P < 0.001 respectively). Moreover HMGB-1 (P < 0.001), OPG (P < 0.001), HsCRP (P < 0.001) and IL-6 (P < 0.001) serum levels were positively correlated with clinical severity of PAD. HMGB-1 (adjusted OR 12.32; 95% CI 3.56-23.54, P = 0.023) and OPG (adjusted OR 3.53; 95% CI 1.54-6.15, P = 0.019) resulted independent determinants of PAD in patients with T2D after adjusting for the conventional cardiovascular risk factor and established inflammatory mediators. Conclusions: In T2D patients HMGB-1 and OPG serum levels are higher in patients affected by PAD and independently associated with its occurrence and clinical severity.

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