Diabetic Complications - Neuropathy

Clinical manifestations

• Sensorimotor polyneuropathy
  Longer nerve fibers are affected to a greater degree than shorter ones, because nerve conduction velocity is slowed in proportion to a nerve's length. In this syndrome, decreased sensation and loss of reflexes occurs first in the toes bilaterally, then extends upward. It is usually described as glove-stocking distribution of numbness, sensory loss, dysesthesia and nighttime pain.
• Autonomic neuropathy
  The autonomic nervous system is composed of nerves serving the heart, gastrointestinal system and urinary-genital system. Autonomic neuropathy can affect any of these organ systems. The most commonly recognized autonomic dysfunction in diabetics is orthostatic hypotension, or the uncomfortable sensation of fainting when a patient stands up. In the case of diabetic autonomic neuropathy, it is due to the failure of the heart and arteries to appropriately adjust heart rate and vascular tone to keep blood continually and fully flowing to the brain.
• Cranial neuropathy
  When cranial nerves are affected, oculomotor (3rd) neuropathies are most common. The oculomotor nerve controls all of the muscles that move the eye with the exception of the lateral rectus and superior oblique muscles. It also serves to constrict the pupil and open the eyelid. The onset of a diabetic third nerve palsy is usually abrupt, beginning with frontal or periorbital pain and then diplopia. All of the oculomotor muscles innervated by the third nerve may be affected, except for those that control pupil size.

Pathology and pathogenesis

There are four factors thought to be involved in the development of diabetic neuropathy:

• Microvascular disease,
• Advanced Glycation Endproduct,
• Protein kinase C, and the
• Polyol pathway.

Microvascular disease

Advanced glycated end products

Elevated intracellular levels of glucose cause a non-enzymatic covalent bonding with proteins, which alters their structure and destroys their function. Some of these glycosylated proteins have been implicated in the pathology of diabetic neuropathy and other long term complications of diabetes.

Protein kinase C (PKC)

PKC is implicated in the pathology of diabetic neuropathy. Increased levels of glucose cause an increase in intracellular diacylglycerol, which activates PKC. PKC inhibitors in animal models will increase nerve conduction velocity by increasing neuronal blood flow.

Polyol pathway

Also called the Sorbitol/Aldose Reductase Pathway, the Polyol Pathway may be implicated in diabetic complications that result in microvascular damage to nervous tissue, and also to the retina and kidney which also have lots of microvasculature themselves.

Source: Wikipedia

All you wanted to know about this hot research subject condensed in a few illustrated pages

Dr A. Gugliucci

What do crust pies, cola drinks, coffee, dulce de leche ice cream and your body proteins have in common, especially if you suffer from diabetes? The brown pigments in these foodstuffs contain Maillard reaction products, which are condensations of sugars and proteins at high temperatures. Similar reactions, but at lower temperatures but over far longer periods of time, occur in our bodies and may be involved in aging and diabetic complications. This is the sour side of sugars, their excess can lead to severe modifications of our proteins and their excess is precisely one of the characteristics of diabetes. We offer here a brief synopsis of the main points regarding this topic.

Peripheral neuropathy: pathogenic mechanisms and alternative therapies

Altern Med Rev. 2006 Dec;11(4):294-329

Head KA.

Peripheral neuropathy (PN), associated with diabetes, neurotoxic chemotherapy, human immunodeficiency virus (HIV)/antiretroviral drugs, alcoholism, nutrient deficiencies, heavy metal toxicity, and other etiologies, results in significant morbidity. Conventional pain medications primarily mask symptoms and have significant side effects and addiction profiles. However, a widening body of research indicates alternative medicine may offer significant benefit to this patient population. Alpha-lipoic acid, acetyl-L-carnitine, benfotiamine, methylcobalamin, and topical capsaicin are among the most well-researched alternative options for the treatment of PN. Other potential nutrient or botanical therapies include vitamin E, glutathione, folate, pyridoxine, biotin, myo-inositol, omega-3 and -6 fatty acids, L-arginine, L-glutamine, taurine, N-acetylcysteine, zinc, magnesium, chromium, and St. John's wort. In the realm of physical medicine, acupuncture, magnetic therapy, and yoga have been found to provide benefit. New cutting-edge conventional therapies, including dual-action peptides, may also hold promise.

Publication Types:

• Review

Publication Types:

• Review