2型糖尿病患者阻塞性睡眠呼吸暂停与表皮内神经纤维密度、PARP激活及足部溃疡之间的关系。

The relationship between obstructive sleep apnea and intra-epidermal nerve fiber density, PARP activation and foot ulceration in patients with type 2 diabetes.

作者信息

Altaf Quratul-Ain Altaf, Ali Asad, Piya Milan K, Raymond Neil T, Tahrani Abd A

机构信息

Department of Diabetes and Endocrinology, Heart of England NHS Foundation Trust, Birmingham, UK; Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

Department of Respiratory Medicine, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK.

出版信息

J Diabetes Complications. 2016 Sep-Oct;30(7):1315-20. doi: 10.1016/j.jdiacomp.2016.05.025. Epub 2016 Jun 2.

DOI:10.1016/j.jdiacomp.2016.05.025

PMID:27324704

Abstract

BACKGROUND

Obstructive sleep apnea (OSA) is associated with increased nitrosative stress, endothelial dysfunction, and peripheral neuropathy in patients with type 2 diabetes. We hypothesized that OSA is associated with Poly ADP ribose polymerase (PARP) activation, lower intra-epidermal nerve fiber density (IENFD), and diabetic foot ulceration (DFU).

METHODS

A cross-sectional study of adults with type 2 diabetes recruited from a secondary care hospital in the UK. OSA was assessed by multi-channel home-based cardio-respiratory device (Alice PDX, Philips Respironics). DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI). IENFD and % PAR stained nuclei were assessed using immunohistochemistry staining on skin biopsies. DFU was assessed based on MNSI.

RESULTS

Skin biopsies and DFU data were available from 52 and 234 patients respectively. OSA was associated with lower IENFD (12.75±1.93 vs. 10.55±1.62 vs. 9.42±1.16 fibers/mm of epidermis for no OSA, mild OSA and moderate to severe OSA respectively, p<0.001). Following adjustment, mild (B=-2.19, p=0.002) and moderate to severe OSA (B=-3.45, p<0.001) were independently associated with IENFD. The apnea hypopnea index (AHI) was associated with IENFD following adjustment (B=-2.45, p<0.001). AHI was associated with percentage of PAR stained nuclei following adjustment (B=13.67, p=0.025). DFU prevalence was greater in patients with OSA (7.1% vs. 28.1% vs. 26.2% for patients with no OSA, mild OSA and moderate to severe OSA respectively, p=0.001). Following adjustment, OSA was associated with DFU (OR 3.34, 95% CI 1.19-9.38, p=0.022).

CONCLUSIONS

OSA is associated with lower IENFD, PARP activation and DFU in patients with type 2 diabetes. Our findings suggest that OSA is associated with small fiber neuropathy. PARP activation is a potential mechanisms linking OSA to DPN and endothelial dysfunction in patients with type 2 diabetes. Whether OSA treatment will have a favorable impact on these parameters and DFU requires interventional studies.

摘要

背景

阻塞性睡眠呼吸暂停（OSA）与2型糖尿病患者的亚硝化应激增加、内皮功能障碍和周围神经病变有关。我们假设OSA与聚ADP核糖聚合酶（PARP）激活、表皮内神经纤维密度（IENFD）降低和糖尿病足溃疡（DFU）有关。

方法

对从英国一家二级护理医院招募的成年2型糖尿病患者进行横断面研究。通过多通道家庭心肺设备（Alice PDX，飞利浦伟康）评估OSA。使用密歇根神经病变筛查工具（MNSI）评估糖尿病周围神经病变（DPN）。通过对皮肤活检进行免疫组织化学染色来评估IENFD和PAR染色细胞核的百分比。基于MNSI评估DFU。

结果

分别有52例和234例患者获得了皮肤活检和DFU数据。OSA与较低的IENFD相关（无OSA、轻度OSA和中度至重度OSA患者的表皮神经纤维分别为12.75±1.93、10.55±1.62和9.42±1.16根/mm，p<0.001）。调整后，轻度（B=-2.19，p=0.002）和中度至重度OSA（B=-3.45，p<0.001）与IENFD独立相关。调整后，呼吸暂停低通气指数（AHI）与IENFD相关（B=-2.45，p<0.001）。调整后，AHI与PAR染色细胞核百分比相关（B=13.67，p=0.025）。OSA患者的DFU患病率更高（无OSA、轻度OSA和中度至重度OSA患者的DFU患病率分别为7.1%、28.1%和26.2%，p=0.001）。调整后，OSA与DFU相关（OR 3.34，95%CI 1.19-9.38，p=0.022）。