Autophagy in the posterior interosseous nerve of patients with type 1 and type 2 diabetes mellitus: an ultrastructural study

Abstract

Aims/hypothesis We addressed the question of whether the autophagy pathway occurs in human peripheral nerves and whether this pathway is associated with peripheral neuropathy in diabetes mellitus. Methods By using electron microscopy, we evaluated the presence of autophagy-related structures and neuropathy in the posterior interosseous nerve of patients who had undergone carpal tunnel release and had type 1 or type 2 diabetes mellitus, and in patients with no diabetes (controls). Results Autophagy-related ultrastructures were observed in the samples taken from all patients of the three groups. The number of autophagy-associated structures was significantly higher ( p<0.05) in the nerves of patients with type 1 than type 2 diabetes. Qualitative and quantitative evaluations of fascicle area, diameter of myelinated and unmyelinated nerve fibres, the density of myelinated and unmyelinated fibres and the gratio of myelinated fibres were performed. We found degeneration and regeneration of a few myelinated axons in controls, and a well-developed neuropathy with the loss of large myelinated axons and the presence of many small ones in patients with diabetes. The pathology in type 1 diabetes was more extensive than in type 2 diabetes. Conclusions/interpretation The results of this study show that the human peripheral nerves have access to the autophagy machinery, and this pathway may be regulated differently in type 1 and type 2 diabetes; insulin, presence of extensive neuropathy, and/or other factors such as duration of diabetes and HbA 1c level may underlie this differential regulation.

Longitudinal study of neuropathy, microangiopathy, and autophagy in sural nerve: Implications for diabetic neuropathy

“…However, in the present study we show no difference in the density of autophagy structures in subjects with NGT, IGT, and T2DM at baseline, which is in agreement with our recent study showing no difference in autophagy structures in the posterior interosseous nerve of patients with T2DM (Osman et al, 2015). Furthermore, in the current study, we demonstrate a significant decrease in autophagy structures in the myelinated axons of patients with T2DM at follow-up, despite increasing severity of neuropathy evidenced by worsening neurophysiology and nerve fiber pathology.…”

“…Thus, experimental data suggests that autophagic turnover may help to maintain healthy mitochondria and energyderived metabolic processes, limiting cellular death pathways, oxidative stress, and protein aggregation in diabetic neuropathy (Yerra, Gundu, Bachewal, & Kumar, 2016). Indeed, we have recently reported a more severe loss of large myelinated nerve fibers and increased unmyelinated fiber regeneration with a significant increase in autophagy structures in the posterior interosseous nerve of patients with type 1 compared to type 2 diabetes (Osman, Dahlin, Thomsen, & Mohseni, 2015).…”

Open carpal tunnel release and diabetes: a retrospective study using PROMs and national quality registries

“…Even though small numbers, patients with type 1 diabetes reported similar outcome as patients with type 2 diabetes, despite longer duration of diabetes, higher prevalence of retinopathy and higher HbA1c levels. Neuropathy in peripheral nerves is more severe in type 1 diabetes than in type 2 diabetes,49 which would indicate a higher risk for developing CTS and for an unfavourable outcome. However, QuickDASH scores were higher in the type 2 diabetes patients before surgery, indicating worse symptoms of CTS.…”

Improved metabolic control using glucose monitoring systems leads to improvement in vibration perception thresholds in type 1 diabetes patients

“…It is estimated that prevalence of DSPN in patients with type 1 diabetes (T1DM) is at least 20% after 20 years of disease duration [1]. Although DSPN is often considered irreversible, some studies suggest that both peripheral neuropathy and autonomous neuropathy can be reversed in specific cases [2][3][4][5], even if structural changes are present with degeneration and regenerative clusters [6]. Normalization of blood glucose by pancreas transplantation can improve nerve function in T1DM patients with DSPN [2], although severe nerve fibre loss seems to be irreversible [7].…”