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

Abstract

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.

Obstructive Sleep Apnea and Retinopathy in Patients with Type 2 Diabetes. A Longitudinal Study

“…In addition, endothelial dysfunction plays an important role in the development of DR and maculopathy. We and others have previously shown that OSA (and its associated cyclical oxygen desaturations and disruptions in sleep architecture) can lead to the activation of poly(ADP-ribose) polymerase, protein kinase C, and the polyol pathway, as well as increased advanced glycation end product production, inflammation, and oxidative and nitrosative stress, all of which can lead to endothelial dysfunction and could have contributed to the observed associations between OSA and DR in our study (10,30,31).…”

Elevated obstructive sleep apnoea risk score is associated with poor healing of diabetic foot ulcers: a prospective cohort study

“…In patients with diabetes and OSA, intermittent hypoxia increases sympathetic activation and thereby oxidative stress, impaired microvascular function and inflammation, which could all contribute to poorer diabetic foot ulcer outcomes [8]. In a cross-sectional study in people with Type 2 diabetes, OSA was associated with diabetic foot ulcers, and this association was independent of risk factors such as peripheral artery disease, BMI, age, diabetes duration and HbA 1c level [9]. In a recent case series of three people with diabetic foot ulcers, the authors hypothesized that undiagnosed or untreated severe OSA contributed to failure of diabetic foot ulcer healing and reported that initiation of OSA treatment improved ulcer healing [18].…”

“…In another cross-sectional study in people with Type 2 diabetes, 64% were diagnosed with co-existent OSA and the authors observed a more than threefold higher prevalence of a history of diabetic foot ulcers in those with OSA (26.2% vs 7.1%) as compared to those without OSA [8]. The same group also described increased activation of markers of oxidative stress, pro-inflammatory cytokines and lower intra-epidermal nerve fibre density in patients with OSA [9]. In parallel, intermittent hypoxia and subsequent reoxygenation may lead to hypoxia/reperfusion injury with resultant increased oxidative stress and production of vascular growth factors which can further impair wound healing [8,10].…”

The Epidemiology of Sleep and Diabetes

“…Evidence for a cross-sectional association between OSA and diabetic neuropathy in type 2 diabetes is mixed with more consistent evidence for an association in type 1 diabetes [127]. Nevertheless, one study found OSA is associated with foot ulcers in type 2 diabetes [128]. No randomized trials have yet evaluated whether treating OSA can prevent or improve microvascular complications.…”