Interactions between and Shared Molecular Mechanisms of Diabetic Peripheral Neuropathy and Obstructive Sleep Apnea in Type 2 Diabetes Patients

Abstract

Type 2 diabetes (T2D) accounts for about 90% of all diabetes patients and incurs a heavy global public health burden. Up to 50% of T2D patients will eventually develop neuropathy as T2D progresses. Diabetic peripheral neuropathy (DPN) is a common diabetic complication and one of the main causes of increased morbidity and mortality of T2D patients. Obstructive sleep apnea (OSA) affects over 15% of the general population and is associated with a higher prevalence of T2D. Growing evidence also indicates that OSA is highly prevalent in T2D patients probably due to diabetic peripheral neuropathy. However, the interrelations among diabetic peripheral neuropathy, OSA, and T2D hitherto have not been clearly elucidated. Numerous molecular mechanisms have been documented that underlie diabetic peripheral neuropathy and OSA, including oxidative stress, inflammation, endothelin-1, vascular endothelial growth factor (VEGF), accumulation of advanced glycation end products, protein kinase C (PKC) signaling, poly ADP ribose polymerase (PARP), nitrosative stress, plasminogen activator inhibitor-1, and vitamin D deficiency. In this review, we seek to illuminate the relationships among T2D, diabetic peripheral neuropathy, and OSA and how they interact with one another. In addition, we summarize and explain the shared molecular mechanisms involved in diabetic peripheral neuropathy and OSA for further mechanistic investigations and novel therapeutic strategies for attenuating and preventing the development and progression of diabetic peripheral neuropathy and OSA in T2D.

Thinning of Macular Neuroretinal Layers Contributes to Sleep Disorder in Patients With Type 2 Diabetes Without Clinical Evidences of Neuropathy and Retinopathy

“…In patients with type 2 diabetes, sleep disorder, especially obstructive sleeping apnea, is associated with diabetic peripheral neuropathy (11) and autonomic neuropathy (41). The altered median nerve amplitude, CVR-R, and beading structures of corneal nerve fibers were associated with the increased PSQI-J scores.…”

“…Although the temporal structures of daily life influence sleep, their impacts on the macular neuroretinal layer thickness had never been reported. Diabetic retinopathy and neuropathy influence the thickness of the macular neuroretinal layers (8,9) and sleep disorder (10,11); however, these have not been investigated in detail. Recently, Dumpala et al (12) reported that the thinning and dysfunction of the outer retina in the small number of patients with type 2 diabetes may contribute to poor sleep behavior.…”

Therapeutic effects of moxibustion simultaneously targeting Nrf2 and NF-κB in diabetic peripheral neuropathy

“…According to the World Health Organization (WHO), the prevalence of diabetes mellitus is predicted to increase by 170% between 1995 and 2025 [1]; furthermore, 353 million individuals will suffer from diabetes mellitus by 2030 [2]. Diabetic neuropathy is the most common complication associated with peripheral neuropathy; this condition may be caused by diseases, nerve trauma, or side effects induced by systemic illness [3]. Diabetic neuropathy also results in large disease burdens, such as incapacity to work, poor quality of life, and consumption of health care resources [4].…”

Inspiratory Muscle Training in Obstructive Sleep Apnea Associating Diabetic Peripheral Neuropathy: A Randomized Control Study

“…In addition, mechanisms including oxidative stress, inflammation, AGEs, and PKC signaling contributed to DPN and OSA. These underlying mechanisms may occur simultaneously in patients with T2D leading to DPN and OSA [19][20][21].…”