Diabetic Neuropathies - Long Term Complications of Diabetes

DIABETIC NEUROPATHIES

Diabetic neuropathy refers to a group of diseases that affect all types of nerves, including peripheral (sensorimotor), autonomic, and spinal nerves. The disorders appear to be clinically diverse and depend on the location of the affected nerve cells. The preva-lence increases with the age of the patient and the duration of the disease and may be as high as 50% in patients who have had di-abetes for 25 years.

Elevated blood glucose levels over a period of years have been implicated in the etiology of neuropathy. The pathogenesis of neuropathy may be attributed to either a vascular or a metabolic mechanism or both, but their relative contributions have yet to be determined. Capillary basement membrane thickening and capillary closure may be present. In addition, there may be de-myelinization of the nerves, which is thought to be related to hyperglycemia. Nerve conduction is disrupted when there are aberrations of the myelin sheaths. Control of blood glucose levels to normal or near-normal levels was shown in the DCCT study to decrease the incidence of neuropathy by 60%.

The two most common types of diabetic neuropathy are sen-sorimotor polyneuropathy and autonomic neuropathy. Cranial mononeuropathies, for example, those affecting the oculomotor nerve, also occur in diabetes, especially among the elderly.

Sensorimotor polyneuropathy is a diabetic neuropathy also called peripheral neuropathy. It most commonly affects the dis-tal portions of the nerves, especially the nerves of the lower ex-tremities. It affects both sides of the body symmetrically and may spread in a proximal direction.

Peripheral Neuropathy

CLINICAL MANIFESTATIONS

Initial symptoms include paresthesias (prickling, tingling, or heightened sensation) and burning sensations (especially at night). As the neuropathy progresses, the feet become numb. In addition, a decrease in proprioception (awareness of posture and movement of the body and of position and weight of ob-jects in relation to the body) and a decreased sensation of light touch may lead to an unsteady gait. Decreased sensations of pain and temperature place patients with neuropathy at in-creased risk for injury and undetected foot infections. Defor-mities of the foot may also occur, with neuropathy-related joint changes producing Charcot joints. These joint deformities re-sult from the abnormal weight distribution on joints due to lack of proprioception.

On physical examination, a decrease in deep tendon reflexes and vibratory sensation is found. For patients who have few or no symptoms of neuropathy, these physical findings may be the only indication of neuropathic changes. For patients with signs or symptoms of neuropathy, it is important to rule out other possible neuropathies, including alcohol-induced or vitamin-deficiency neuropathies.

MANAGEMENT

The results of the DCCT study demonstrate that intensive in-sulin therapy and control of blood glucose levels delay the onset and slow the progression of neuropathy. Pain, particularly of the lower extremities, is a disturbing symptom in some people with neuropathy secondary to diabetes. For some patients, neuro-pathic pain spontaneously resolves within 6 months. For other patients, pain persists for many years. Various approaches to pain management can be tried. These include analgesics (preferably nonopioid); tricyclic antidepressants; phenytoin, carbamazepine, or gabapentin (antiseizure medications); mexiletine (an anti-arrhythmic); or transcutaneous electrical nerve stimulation (TENS).

The use of aldose reductase inhibitors is under study to deter-mine whether they block the damaging effects of hyperglycemia. The topical medication capsaicin (Axscain) also has been shown in preliminary reports to decrease lower-extremity neuropathic pain. Studies of the role of this topical medication in neuropathy continue.

Autonomic Neuropathies

Neuropathy of the autonomic nervous system results in a broad range of dysfunctions affecting almost every organ system of the body. Three manifestations of autonomic neuropathy are related to the cardiac, GI, and renal systems Cardiovascular symptoms range from fixed, slightly tachycardic heart rate; orthostatic hypo-tension; and silent, or painless, myocardial ischemia and in-farction. Delayed gastric emptying may occur with the typical symptoms of early satiety, bloating, nausea, and vomiting. In ad-dition, there may be unexplained wide swings in blood glucose levels related to inconsistent absorption of the glucose from ingested foods secondary to the inconsistent gastric emptying. “Diabetic” constipation or diarrhea (especially nocturnal diarrhea) may occur as a result.

Urinary retention, a decreased sensation of bladder fullness, and other urinary symptoms of neurogenic bladder result from autonomic neuropathy. Patients with a neurogenic bladder are predisposed to developing urinary tract infections due to inability to completely empty the bladder. This is especially true in pa-tients with poorly controlled diabetes, because hyperglycemia impairs resistance to infection

HYPOGLYCEMIC UNAWARENESS

Autonomic neuropathy of the adrenal medulla is responsible for diminished or absent adrenergic symptoms of hypoglycemia. Pa-tients may report that they no longer feel the typical shakiness, sweating, nervousness, and palpitations associated with hypo-glycemia. Strict blood glucose monitoring, including frequent SMBG, is recommended for these patients. Their inability to de-tect and treat these warning signs of hypoglycemia puts them at risk for developing dangerously low blood glucose levels. There-fore, their goals for blood glucose levels may need to be adjusted to reduce the risk for hypoglycemia. The patient and family need to be taught to recognize subtle signs and symptoms of hypo-glycemia (Tkacs, 2002).

SUDOMOTOR NEUROPATHY

This neuropathic condition refers to a decrease or absence of sweating (anhidrosis) of the extremities, with a compensatory in-crease in upper body sweating. Dryness of the feet increases the risk for the development of foot ulcers.

SEXUAL DYSFUNCTION

Sexual dysfunction, especially impotence in men, is a complica-tion of diabetes. The effects of autonomic neuropathy on female sexual functioning are not well documented. Reduced vaginal lubrication has been mentioned as a possible neuropathic effect; other possible changes in sexual function in women with diabetes include decreased libido and lack of orgasm. Vaginal infection, increased in incidence in women with diabetes, may be associated with decreased lubrication and vaginal itching and tenderness. Urinary tract infections and vaginitis may also affect sexual func-tion (Tilton, 1997).

Impotence (inability of the penis to become rigid and sustain an erection adequate for penetration) occurs with greater fre-quency in diabetic men than in nondiabetic men of the same age. However, diabetic neuropathy is not the only cause of impotence in men with diabetes. Medications such as antihypertensive agents, psychological factors, and other medical conditions (eg, vascular insufficiency) that may affect nondiabetic men also play a role in impotence in diabetic men.

Some men with autonomic neuropathy have normal erectile function and can experience orgasm but do not ejaculate. Retro-grade ejaculation occurs: seminal fluid is propelled backward through the posterior urethra and into the urinary bladder. Ex-amination of the urine confirms the diagnosis because of the large number of active sperm present. Fertility counseling is necessary for couples attempting conception.

MANAGEMENT

Management strategies depend on the symptoms. There is no treatment for painless cardiac ischemia, and the prognosis is poor. Detection, however, is important so that education about avoid-ing strenuous exercise can be provided. Orthostatic hypotension may respond to a diet high in sodium, the discontinuation of medications that impede autonomic nervous system responses, the use of sympathomimetics and other agents (eg, caffeine) that stimulate an autonomic response, and the use of lower-body elas-tic garments that maximize venous return and prevent pooling of blood in the extremities.

Treatment of delayed gastric emptying includes a low-fat diet, frequent small meals, close blood glucose control, and use of agents that increase gastric motility (eg, metoclopramide, bethanechol). Treatment of diabetic diarrhea may include bulk-forming laxatives or antidiarrheal agents. Constipation is treated with a high-fiber diet and adequate hydration; medications, lax-atives, and enemas may be necessary when constipation is severe.

Treatment of sudomotor dysfunction focuses on education about skin care and heat intolerance.