What Emerging Research Reveals About Hyperglycemia And Vascular Imbalances

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Although more than half of patients with diabetes will develop neuropathy, such as the patient shown above, the author says not much is known about the epidemiology and natural history of diabetic neuropathy. (Photo courtesy of Stephen Barrett, DPM)
What Emerging Research Reveals About Hyperglycemia And Vascular Imbalances
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Author(s): 
By Javier La Fontaine, DPM

      Research is an essential part of medicine when it comes to the ongoing improvement of patient care. Although podiatry is still very early into its development of consistent research contributions, research in diabetes has an impact in what we do daily. Research on topics such as diabetic neuropathy, vascular disease, wound care, the management of diabetes and offloading should be of interest.

      Diabetic neuropathy has been identified as an important risk factor for foot problems in the diabetic patient. The cost of diabetic neuropathy and its consequences to the U.S. healthcare system amount to approximately $13.7 billion dollars annually. About 50 to 60 percent of patients with diabetes will develop neuropathy and 15 percent of patients with diabetes will develop an ulcer in their lifetimes.

      Patients with diabetic neuropathy do not always have pain but for those who do, the Food and Drug Administration (FDA) has approved duloxetine (Cymbalta, Eli Lilly) and pregabalin (Lyrica, Pfizer) for the management of painful diabetic neuropathy. These are the only two drugs with an indication to treat this entity.

      However, little is known about the epidemiology and natural history of diabetic neuropathy. Many researchers have spent their entire careers investigating the etiology of neuropathy, and have concluded that hyperglycemia is the most important factor leading to the development and severity of neuropathy.

      That is not to say that other etiologies may play a role. The Rochester Neuropathy Study demonstrated that the cause of the neuropathy in 10 percent of the diabetic patients was due to other etiologies than diabetes.1
Deficiency of growth factors, advanced glycosylated end product accumulation, immune mechanisms, glucose auto-oxidation, and PKC-inhibition activation are among other etiologies advocated in the medical literature.

      However, it is clear that hyperglycemia plays a central role in creating the vascular imbalances that are so unique to the diabetic process. Glucose does not directly cause adverse changes to the vascular system. These changes are accomplished indirectly through the alteration of multiple metabolic pathways. This sequence of events leads to early changes in functional flow and pressure as well as late structural changes that ultimately compromise the ability of the microvasculature, namely the endothelium, to carry out its functions in an ever changing vascular environment. These disturbances eventually may involve capillary closure, extinction, thrombosis or non-perfusion.

      Peripheral vascular disease is present in approximately 15 percent of patients who have a 10-year history of diabetes and in 45 percent of patients who have a greater than 20-year history of diabetes. Vascular insufficiency accounts for 10 to 15 percent of diabetic ulcers.2 A lack of blood flow inhibits the ability to fight infection by decreasing oxygen, nutrient and antibiotic delivery to the site of the infection/ulcer.

Understanding The Impact Of Microvascular And Macrovascular Diseases In Patients With Diabetes

      Macrovascular diseases such as atherosclerosis are also common among those with diabetes. Patients with diabetes may present with a spectrum of lower extremity vascular disease in both the macrovasculature and microvasculature. This spectrum correlates with the duration and degree of diabetes, the presence of comorbid risk factors, such as dyslipidemia, obesity, hypertension and smoking, family history and anatomic location (i.e. proximal versus distal).

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