A Painful Reality: The Vascular Roots of Diabetic Neuropathy

Diabetes mellitus is a major cause of painful diabetic neuropathy (PDN), a distressing condition that makes walking difficult and disrupts sleep. Growing evidence indicates that PDN is closely associated with dysfunction of the microvasculature. Specifically, researchers have found PDN patients often suffer from microangiopathy,¹meaning the walls of the capillaries thicken, blood flow is reduced, and the vessels leak proteins. 

It has long been known that diabetes is implicated in vascular problems, evidenced by increased risk of cardiovascular disease, retinopathy, hypertension, and peripheral vascular disease.^2,3,4  So it is not surprising that the microvasculature, and its degradation resulting from excess blood glucose, is involved in PDN, one of the most common complications suffered by diabetic patients. 

From a clinical perspective, the question is: How best to mitigate the assault on the vasculature unleashed by diabetes?

One answer is to focus on the body’s own “first line of defense.” This is the endothelial glycocalyx (EGX): a microscopically thin, highly dynamic, and semi-permeable matrix that lines the entire endothelium and mediates contact with the flowing blood. Comprised of proteoglycans, glycoproteins, and glycosaminoglycans, the EGX mediates the passage of contents of the blood through the vessel walls, while ensuring the integrity of the endothelium.⁵

The endothelial glycocalyx

The EGX performs several functions that are specifically relevant to diabetic neuropathy. It triggers the endothelium to produce nitric oxide, which is an essential vasodilator. It houses important antioxidant components, especially extracellular superoxide dismutase (exSOD).  Research has indicated a direct correlation between reduced vasodilation and the development of neuropathy.⁶ There is also a correlation with increased oxidative stress.⁷ More broadly, a healthy EGX is essential to a healthy microvasculature: you can’t have one without the other.

The EGX is known to be vulnerable to metabolic insults, in particular an excess of glucose in the blood, so diabetes poses a significant threat to its integrity.⁸

While the EGX may be the first essential structure to fail in the presence of diabetes, it can also be among the first to be restored. This highly dynamic barrier responds quickly to rhamnan sulfate, a polysaccharide found in a rare green seaweed called Monostroma nitidum. This particular polysaccharide is the primary component of Arterosil.

The effectiveness of Arterosil in restoring the EGX has been well established, bringing multiple benefits of a healthier microvasculature.

Learn More

To learn more about Arterosil and new approaches to vascular health, explore this video where Dr. Burke explains the science around and therapeutics for the endothelial glycocalyx.

References

1. Dahl-Jørgensen, K. Diabetic Microangiopathy. Acta Paediatrica, vol. 87, no. s425, 1998, pp. 31–34, doi:10.1111/j.1651-2227.1998.tb01249.x.
2. Donnelly, Richard, et al. Vascular Complications of Diabetes. BMJ, vol. 320, no. 7241, Apr. 2000, pp. 1062–66, doi:10.1136/bmj.320.7241.1062.
3. Cameron, N. E., et al. Vascular Factors and Metabolic Interactions in the Pathogenesis of Diabetic Neuropathy. Diabetologia, vol. 44, no. 11, Nov. 2001, pp. 1973–88
4. Feener, Edward P., and George L. King. Vascular Dysfunction in Diabetes Mellitus. The Lancet, vol. 350, July 1997, pp. S9–13, doi:10.1016/S0140-6736(97)90022-2.
5. Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 2007;454(3):345-359. 
6. Veves, A., et al. Endothelial Dysfunction and the Expression of Endothelial Nitric Oxide Synthetase in Diabetic Neuropathy, Vascular Disease, and Foot Ulceration. Diabetes, vol. 47, no. 3, Mar. 1998, pp. 457–63, 
7. Feldman, Eva L. Oxidative Stress and Diabetic Neuropathy: A New Understanding of an Old Problem. The Journal of Clinical Investigation, vol. 111, no. 4, Feb. 2003, pp. 431–33,
8. Lopez-Quintero, Sandra V., et al. High Glucose Attenuates Shear-Induced Changes in Endothelial Hydraulic Conductivity by Degrading the Glycocalyx. PLOS ONE, vol. 8, no. 11, Nov. 2013, p. e78954, doi:10.1371/journal.pone.0078954.

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