Thus, small blood vessel dysfunction occurs early in diabetes, parallels the progression of neural dysfunction, and may be sufficient to support the severity of structural, functional, and clinical changes observed in diabetic neuropathy. Advanced glycated end products
Elevated levels of glucose within cells cause a non-enzymatic covalent bonding with proteins, which alters their structure and inhibits their function. Some of these glycated proteins have been implicated in the pathology of diabetic neuropathy and other long-term complications of diabetes. Polyol pathway
Also called the sorbitol/aldose reductase pathway, the polyol pathway appears to be implicated in diabetic complications, especially in microvascular damage to the retina, kidney, and nerves. Diagnosis
Diabetic peripheral neuropathy can be diagnosed with a history and physical examination. The diagnosis is considered in people who develop pain or numbness in a leg or foot with a history of diabetes. Muscle weakness, pain, balance loss, and lower limb dysfunction are the most common clinical manifestations. Physical exam findings may include changes in appearance of the feet, presence of ulceration, and diminished ankle reflexes. The most useful physical examination finding for large fiber neuropathy is an abnormally decreased vibration perception to a 128-Hz tuning fork (likelihood ratio (LR) range, 16–35) or pressure sensation with a 5.07 Semmes-Weinstein monofilament (LR range, 11–16). Normal results on vibration testing (LR range, 0.33–0.51) or monofilament (LR range, 0.09–0.54) make large fiber peripheral neuropathy from diabetes less likely.
These patients cannot feel when they are stepping on a foreign body, like a splinter, or when they are developing a callus from an ill-fitting shoe. Consequently, they are at risk of developing ulcers and infections on the feet and legs, which can lead to amputation. Similarly, these patients can get multiple fractures of the knee, ankle or foot, and develop a Charcot joint. Loss of motor function results in dorsiflexion, contractures of the toes, loss of the interosseous muscle function that leads to contraction of the digits, so-called hammer toes. These contractures occur not only in the foot but also in the hand where the loss of the musculature makes the hand appear gaunt and skeletal. The loss of muscular function is progressive. Autonomic neuropathy
The autonomic nervous system is composed of nerves serving the heart, lungs, blood vessels, bone, adipose tissue, sweat glands, gastrointestinal system and genitourinary system. Autonomic neuropathy can affect any of these organ systems. One commonly recognized autonomic dysfunction in diabetics is orthostatic hypotension, or becoming dizzy and possibly fainting when standing up due to a sudden drop in blood pressure. 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. This symptom is usually accompanied by a loss of respiratory sinus arrhythmia – the usual change in heart rate seen with normal breathing.