I. Introduction
Diabetes is on the rise in the United States and the resultant health problems are leading to visits to physicians’ offices and hospitals more than ever before. Diabetic neuropathy, a debilitating nerve disorder which can affect almost any part of the nervous system, occurs in nearly 50 percent of patients with diabetes. Diabetic peripheral neuropathy is found in 12 percent of insulin dependent diabetics and 32 percent of those who are not, equaling approximately 3 million people in the United States. (Chen et al. 2007) The number of patients with other neuropathies, such as autonomic, proximal, and focal, comprises the other 1 million diabetic neuropathy patients, most of whom suffer in pain from the dysfunction of the nervous system. (Chen et al. 2007) This disorder’s elusive nature is such that it can not only present in any part of the body but it can be completely without symptoms that the average patient would report to their physician. Since the patients themselves are less likely to naturally disclose their suffering through their assumption that their symptoms are not relevant to their diabetic condition, the physician’s role in the diagnosis and recognition of this disorder is even more critical.

II. Definition and Types of Diabetic Neuropathy
The most common type of diabetic neuropathy is peripheral, considered, more generally, sensorimotor. Peripheral neuropathy causes pain or loss of feeling in the toes, feet, legs, hands, and arms. (NIDDKD 2002) Specifically, distal symmetric polyneuropathy is the most common of peripheral types, causing nerve damage away from the center of the nervous system but equally on both sides of the body and in multiple places. Thus, the extremities are most affected. Peripheral neuropathy may cause not only pain but muscle weakness and early fatigue and loss of reflexes. Foot deformities, such as hammertoes and the collapse of the instep, are not uncommon. As parts of the foot become numb, blisters and sores may occur where pressure or injury are no longer noticed. (NIDDKD 2002) Of other types of sensorimotor neuropathies, proximal and focal are also possible in the diabetic patient. Proximal neuropathy often presents as pain in the thighs, hips, or buttocks. Weakness in the legs is also symptomatic of a proximal neuropathic condition. Focal neuropathy (known as diabetic mononeuropathy), which refers to damage to an asymmetric nerve or group of nerves, can cause muscle weakness or pain in any nerve of the body. (NIDDKD 2002, Aring et al. 2005) Autonomic neuropathies, although less common than sensorimotor, present in the vital areas of the body. They are generally classified by the affected system, such as the endocrine, gastrointestinal, genitourinary, and cardiovascular. (Aring et al. 2005) Autonomic neuropathy leads to disruption in digestion, bowel and bladder function, perspiration, and sexual response. It can also damage the nerves that control both the heart rate and blood pressure. Autonomic neuropathy can also lead to patient unawareness of the onset of hypoglycemia (low blood sugar), leading to life threatening situations and possible diabetic shock or coma. (Aring et al. 2005) In clinical studies, researchers have found that autonomic nerve damage may include exercise intolerance, no variation in heart rate during activities, persistent sinus tachycardia, and bradycardia. (Aring et al. 2005)

III. A Diabetes-Neuropathy Causation Analysis
It is clear from clinical results that diabetic patients suffer neuropathies in much larger numbers than the general population. The causal connection between these two disorders is due to a number of factors, all hinging on the presence of sustained high blood glucose. Therefore, neuropathies present more often in patients who remain undiagnosed for a period of time. It also presents in patients who have been suffering from diabetes for a number of years. The nerve damage itself is caused by some combination of the following factors, as outlined by the National Institute of Diabetes and Digestive and Kidney Diseases: “…metabolic factors, such as high blood glucose, long duration of diabetes, possibly low levels of insulin, and abnormal blood fat levels; neurovascular factors, leading to damage to the blood vessels that carry oxygen and nutrients to the nerves; autoimmune factors that cause inflammation in nerves; mechanical injury to nerves, such as carpal tunnel syndrome; inherited traits that increase susceptibility to nerve disease; lifestyle factors such as smoking or alcohol use.” (NIDDKD 2002) Sensory nerve damage occurs first in the nerves with the longest axons, resulting in a stocking-and-glove distribution. The sensation of temperature, light touch, pinprick, and pain is caused by small fiber damage. Large fiber damage is responsible for changes in vibratory sensation, sense of positionality, muscle strength, discrimination between sharp and dull pain sensations, and two-point discrimination. (Aring et al. 2005) Some data suggests that certain nerve fibers are more susceptible to damage than others. Particularly, the small caliber or unmyelinated fibers appear in trials to be the most vulnerable, while others with larger diameters and myelination may be spared, because they can withstand the velocities of normal conduction more readily. In this regard, impaired insulin as well as the altered glucose metabolism might be the disruptive agent in the functioning of the nodes of some larger nerve fibers affected by neuropathy. (Miscio et al. 2006)

IV. Diagnosis and Symptoms
The symptoms of distal symmetric polyneuropathy include variable pain, nerve palsies, motor dysfunction, ulcers, burns, infections, gangrene, and Charcot's disease. It is also possible for patients to develop neuropathic cachexia syndrome, including anorexia, depression, and weight loss. (Aring et al. 2005) The onset of distal symmetric polyneuropathy can be a slow process, building over a number of years. (NIDDKD 2002) Diabetic mononeuropathy, on the other hand, is often acute from the start and presents asymmetrically. The nerves involved are cranial, truncal, or peripheral. This neuropathy, though acute, often resolves spontaneously in less than a year, although in some cases, it can last much longer. (Aring et al. 2005) Symptoms of autonomic damage, such as in the cardiovascular system, can include a change in the body’s ability to adjust blood pressure and heart rate. If blood pressure should drop sharply, for instance, after sitting or standing, the person may experience dizziness and loss of consciousness. Damage to the nerves that control heart rate can cause the heart rate to stay high, rather than rising and falling in a normal fashion. (NDDKD 2002) Nerve damage to the digestive system typically causes constipation, although gastroparesis and diarrhea can also occur. Gastroparesis can cause dangerous fluctuations in blood glucose levels because of the abnormal food digestion. (NDDKD 2002) In addition, most autonomic neuropathy causes damage to the nerves in the organs that control urination and sexual function. (NDDKD 2002) Symptoms of focal neuropathy are: “inability to focus the eye, double vision, aching behind one eye, or paralysis on one side of the face (Bell’s palsy).” (NDDKD 2002) The pain of diabetic neuropathy is most often that of spontaneous burning pain, numbness, and allodynia in the lower extremities. These symptoms commonly exacerbate during sleep, preventing restorative rest and leading to fatigue, irritability, and myofascial dysfunction. (Chen et al. 2004) It is also the case that some patients have no symptoms at all at neuropathy’s onset. For many, the onset of numbness, tingling, or slight pain in the feet comes later in the course of diabetes and may be the first symptoms they experience. Sometimes, a person experiences both pain and numbness together. Often, symptoms begin as fairly minor discomfort, escalating over time, and these mild cases may remain undiagnosed for years. (NDDKD 2002) Regular physician visits is the foundation of any and all neuropathic diagnoses. During these visits, a diabetic should always receive a comprehensive foot exam to assess the health of the skin, circulation, and the ability to sense stimulus. Beyond this, physicians have at their disposal several types of tests to confirm their initial findings. Nerve conduction studies can be conducted to check the transmission of electrical current through a nerve suspected of damage. The image of the nerve that is conducting the electrical signal is projected onto a screen, and a damaged nerve’s impulses will appear slower or weaker than usual. Quantitative sensory testing (QST) is also available, which uses the nerve’s response to stimuli, whether it be pressure, vibration, or temperature, to check for damage. (NDDKD 2002) The primary care physician should also assess the nature and extent of the patient’s pain. Individual pain assessment is largely subjective, so that physicians may use an informal scale to rate their patient’s pain. A pain diagram enables the physician to pinpoint the patient’s experience and locality of pain and allows it to be monitored more precisely. Pain diaries can also be reviewed periodically by the physician which will encourage patient involvement and facilitate outcome assessments. A detailed history of the onset and nature of pain is also important in the process of diagnosis. (Chen et al. 2004) It is also possible for the symptoms and the entire condition of chronic neuropathy to resolve itself without intervention. “The neuropathic pain of CPDN can resolve completely over time in a minority (23%). In these cases, the neuropathy may never return, provided the patient is careful in monitoring and controlling blood glucose levels. [However], in those in whom painful neuropathic symptoms have persisted over 5 years, no significant improvement in pain intensity has been observed.” (Daousi et al. 2006) Despite all the improvements in treatment modalities for chronic pain in recent years, these patients with CPDN may continue to suffer some degree of pain indefinitely.

V. Treatment Options
Unfortunately, advanced understanding of the mechanisms of diabetic neuropathy and its resulting painful symptoms has not led to an ideal treatment model. (Chen et al. 2004) The Diabetes Control Complications Trial (DCCT) recommends tight glycemic control as the best defense, resulting in as much as a 60 percent reduction in the risk of developing clinical neuropathy. (Aring et al. 2005) Normalizing blood glucose levels is the first step in preventing further nerve damage. (NDDKD 2002), adding to the urgency in early diagnosis of diabetes. Historically, neuropathic pain has responded poorly to traditional analgesics. (Chen et al. 2004) However, pharmacological treatments which restore endogenous inhibitory systems, for example, those drugs that mimic descending or local inhibitory pathways (clonidine, tricyclic antidepressants [TCAs], opioids, GABA agonists), have shown some effectiveness in patients. Nonpharmacological techniques such as spinal cord stimulation (SCS), transcutaneous electrical nerve stimulation (TENS), massage, acupuncture, and therapeutic exercise also hold some promise for the relief of pain as well. (Chen et al. 2004) Useful medications exist, though none can be held above the rest as the definitive answer to neuropathic pain. Antidepressants are often prescribed for the more severe symptoms. The possible reasons for this are that antidepressants tend to block the sodium channels and facilitate the endogenous inhibition of pain. Their efficiency then, is not simply a result of the patient experiencing less coincidental depression. (Chen et al. 2004) Antiepileptics are also useful in the treatment of neuropathy because they modulate both peripheral and central mechanisms of impulse reception. (Chen et al. 2004) In treatment of autonomic damage, the ACE inhibitor class of medications appears to protect to some degree against microvascular complications and organ damage from diabetes. (Chong et al. 2007)

VI. The Future of Diabetic Neuropathy
Generally, diabetic neuropathy is most common in people who have had problems controlling their blood glucose levels, in overweight people, in those with high levels of blood fat and elevated blood pressure, those who smoke, as well as in people over the age of 40. (NIDDKD 2002) With the growing problems of obesity and diabetes, in addition to our aging population, the number of patients with glucose-intolerant painful neuropathy can be expected to rise. (Chong et al. 2007) In response, physicians are best armed with a contemporary management approach which relies not only on pharmacological but on nonpharmacological and interventional strategies as well. (Chen et al. 2004) Additionally, interventional strategies such as patient education are crucial to increase patient treatment compliance and to diminish their fears. (Chen et al. 2004) Finally, it is important to note that honesty is also very critical between physicians and those suffering from neuropathies. Patients should understand that complete relief may not occur in all cases. These patients should be reassured that the physician will continue to support them in managing their pain and other symptoms, as well as providing them with new information on prevention and treatments as they become available in the future. (Chen et al. 2004)

I. Introduction A. Statistics B. Commonality C. Elusive Nature of Symptoms II. Definition and Types of Diabetic Neuropathy A. Most Common Types B. Other Types III. A Diabetes-Neuropathy Causation Analysis A. Sustained high blood glucose B. Affect of glucose on axons C. Susceptibility of Certain Nerves IV. Diagnosis and Symptoms A. Pain B. Motor Dysfunction C. Organ/System Dysfunction V. Treatment Options A. Pharmacological B. Nonpharmacological C. Interventional Strategies VI. The Future of Treatment

Works Cited Aring, A.M., D.R. Jones, and J.M. Falko. 2005. Evaluation and Prevention of Diabetic Neuropathy. American Family Physician. 71(11): 2123-2130.

Chen, H., T.J. Lamer, R.H. Rho, K.A. Marshall, B.T. Sitzman, S.M. Ghazi, and R.P. Brewer. 2004. Contemporary Management of Neuropathic Pain for the Primary Care Physician. Mayo Clinic Proceedings. 79(12):1533-1545.

Chong, M.S., and J. Hester. 2007. Diabetic Painful Neuropathy: Current and Future Treatment Options. Drugs. 67:5W-585.

Daousi, C., S. J. Benbow, A. Woodward, and I. A. MacFarlane. 2006. The natural history of chronic painful peripheral neuropathy in a community diabetes population. Diabetic Medicine. 23:1021–1024.

Miscio, G., G. Guastamacchia, A. Brunani, L. Priano, S. Baudo, and A. Mauro. 2006. Obesity and peripheral neuropathy risk: a dangerous liaison. Journal of the Peripheral Nervous System. 10:354–358.

National Institute of Diabetes and Digestive and Kidney Diseases. 2002. Diabetic Neuropathies: The Nerve Damage of Diabetes. National Institutes of Health. NIH Publication No. 02–3185.