Diabetes mellitus peripheral neuropathy

Association of Pain, neuropathic pain is defined as pain initiated or caused by a primary lesion, dysfunction in the nervous system". Neuropathy can be divided broadly into peripheral and central neuropathic pain, depending on whether the primary lesion or dysfunction is situated in the peripheral or central nervous system. In the periphery, neuropathic pain can result from disease or inflammatory states that affect peripheral nerves (e.g. diabetes mellitus, herpes zoster, HIV) or alternatively due to neuroma formation (amputation, nerve transection), nerve compression (e.g. tumours, entrapment) or other injuries (e.g. nerve crush, trauma). Central pain syndromes, on the other hand, result from alterations in different regions of the brain or the spinal cord. Examples include tumour or trauma affecting particular CNS structures (e.g. brainstem and thalamus) or spinal cord injury. Both the symptoms and origins of neuropathic pain are extremely diverse. Due to this variability, neuropathic pain syndromes are often difficult to treat. Some of the clinical symptoms associated with this condition include spontaneous pain, tactile allodynia (touch-evoked pain), hyperalgesia (enhanced responses to a painful stimulus) and sensory deficits. 

Peripheral neuropathies maybe widely disseminated or focal. Patients with disseminated polyneuropathy, whether demyelinative or axonal, usually demonstrate distal sensory and/or motor impairment. Multifocal neuropathy, also referred to as mononeuropathy multiplex, is often a consequence of lesions affecting the vasa nervorum, the blood vessels that supply peripheral nerves. The most common diseases to compromise the vasa nervorum and cause infarction of nerve fascicles are diabetes mellitus and periarteritis nodosa. Other frequent causes of mononeuropathy multiplex include infection (e.g. Lyme disease and leprosy) and multiple compression injury (e.g. bilateral carpal tunnel syndrome). When mononeuropathy... 

Diabetes mellitus is the most common cause of peripheral neuropathy in the United States. Approximately half of all diabetics demonstrate evidences of neuropathy. The usual clinical pattern is that of a slowly progressive, mixed sensorimotor and autonomic polyneuropathy. More acute, asymmetrical motor neuropathies are also seen, usually affecting the lumbosacral plexus, particularly in older persons with type 2 (non-insulin-dependent) diabetes mellitus. Patients with diabetes mellitus are also prone to develop isolated palsies of cranial nerve III or VII, and there is a high incidence of asymptomatic focal demyelin-ation in the distal median nerve. 

Older patients have predominantly Type 2 diabetes mellitus, which shares with Type 1 the risk for retinopathy, nephropathy and neuropathy, but carries a greater risk for macrovascular complications such as coronary artery disease, stroke and peripheral vascular disease. Many such patients have associated obesity, hypertension and hyperlipidemia, compounding the risk of cardiovascular disease. The goals of treatment of DM in the elderly are to decrease symptoms related to hyperglycaemia and to prevent long-term complications. Treatment of type 2 DM can improve prognosis. In the UKPDS trial, sulphonylureas, insulin, and metformin were all associated with a reduction in diabetes-related... 

Certain adverse reactions can also be associated with individuals who are carriers of rare disease genes, patients with compromised immune systems, and patients with certain chronic diseases. Peripheral neuropathy from anticancer drugs such as vincristine can be accelerated in specific patients with Charcot-Marie tooth syndrome [38], Park et al. [39] has discussed potential mechanisms that make HIV-positive patients more susceptible to enhanced drug toxicity, and Graham et al. [40] showed that the risk of developing rhab-domyolysis from statin-fibrin combinations increased significantly in older patients with diabetes mellitus. 

Both formulations of alprostadil are considered more invasive than VEDs or phosphodiesterase inhibitors. For this reason, intracavernosal alprostadil is generally prescribed after patients fail to respond to or cannot use the less invasive interventions. Intracavernosal alprostadil is preferred over intraurethral alprostadil because the former is more effective than the latter. Also, intracavernosal alprostadil may be preferred in patients with diabetes mellitus, who are accustomed to injectable drug therapy and may suffer from peripheral neuropathies, which decreases the patient s perception of pain upon injection. Intraurethral alprostadil is generally reserved as a treatment of last resort for patients who fail other less invasive and more effective forms of therapy and also refuse surgery. 

In contrast to other side effects, peripheral neuropathy has only been observed in the presence of predisposing factors , namely diabetes mellitus, anaemia, B-avitaminosis, or whenever electrolyte balance was disturbed. It may also occur if the NPN (serum nonprotein nitrogen) is over 100 mg per... 

The accumulation of sorbitol in muscle and nerve tissues may contribute to the peripheral neuropathy characteristic of patients with poorly controlled diabetes mellitus. This is one of the reasons it is so important for Di Abietes (who has type 1 diabetes mellitus) and Ann Sulin (who has type 2 diabetes mellitus) to achieve good glycemic control. 

Connective tissue, which consists primarily of fibroblasts, produces extracellular matrix materials that surround cells and tissues, determining their appropriate position within the organ (see Chapter 49). These materials include structural proteins (collagen and elastin), adhesive proteins (fibronectin), and glycosaminoglycans (heparan sulfate, chondroitin sulfate). The unique structures of the proteins and carbohydrates found within the extracellular matrix allow tissues and organs to carry out their many functions. A loss of these supportive and barrier functions of connective tissue sometimes leads to significant clinical consequences, such as those that result from the microvascular alterations that lead to blindness or renal failure, or peripheral neuropathies in patients with diabetes mellitus. 

Diabetic neuropathy was defined at the San Antonio Consensus Conference as a descriptive term meaning a demonstrable nerve disorder, either clinically evident or subclinical, that occurs in the setting of diabetes mellitus without other causes for peripheral neuropathy. The neuropathic disorder includes manifestations in the somatic or autonomic parts of the peripheral nervous system ... 

D. Other serious toxicities that develop after chronic use of many of these agents include bone marrow depression, diabetes mellitus, hepatotoxicity, lactic acidosis, lipodystrophy, lipoatrophy, pancreatitis, peripheral neuropathy, renal failure, and seizures. 

B. Chronic intoxication is also associated with multisystemic effects, which may include fatigue and malaise, gastroenteritis, leukopenia and anemia (occasionally megaloblastic), sensory predominant peripheral neuropathy, hepatic transaminase elevation, nonciiihotic portal hypertension, and peripheral vascular insufficiency. Skin disorders and cancer may occur (see below), and a growing body of epidemiological evidence links chronic arsenic ingestion with an increased risk of hypertension, cardiovascular mortality, and diabetes mellitus. 

Previous exposure to potentially neurotoxic chemotherapeutic agents, such as platinum compounds and vinca alkaloids, does not appear to increase the risk of neurotoxicity with paclitaxel [5 ]. However, patients with co-existing medical illnesses associated with peripheral neuropathy, such as diabetes mellitus and alcohol abuse, may be more likely to develop a peripheral neuropathy. 

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