The metabolic dysregulation associated with DM causes secondary pathophysiologic changes in multiple organ systems that impose a tremendous burden on the individual with diabetes and on the health care system. The two broad categories of DM are designated type 1 and type 2. ALA has been shown to be useful in type 2 diabetes mellitus, and in order to understand the mechanism of action of ALA in control of DM and DM-associated complicating conditions, such as, neuropathy, it is important to understand the pathophysiologic and biochemical mechanism of these conditions (Boulton, 2005).
A prominent biochemical feature of type 2 DM is insulin resistance. This group of disorders is characterised by a pathogenic process that leads to hyperglycemia through variable degrees of insulin resistance, impaired insulin secretion, and increased glucose production. Type 2 DM is characterized by three pathophysiologic abnormalities: impaired insulin secretion, increasing peripheral insulin resistance, and excessive hepatic glucose production. Obesity, particularly visceral or central as evidenced by the hip-waist ratio, is very common in type 2 DM. Adipocytes secrete a number of biologic products, namely, leptin, TFN-alpha, free fatty acids, resistin, and adiponectin that modulate insulin secretion, insulin action, and body weight and may contribute to the insulin resistance. As expected, in the early stage of the disease, glucose tolerance remains normal despite insulin resistance since the pancreatic beta cells compensate by increasing the output of insulin. As insulin resistance and compensatory hyperinsulinemia progress, the pancreatic islets in certain individuals are unable to sustain the hyperinsulinemic state (Huebschmann et al., 2006).
Diabetic neuropathy occurs in approximately 50% of individuals with long-standing type 1 and type 2 DM. It may manifest as polyneuropathy, mononeuropathy, and/or autonomic neuropathy. As with other complications of DM, the development of neuropathy correlates with the duration of diabetes and glycemic control; both myelinated and unmyelinated nerve fibers are lost. Because the clinical features of diabetic neuropathy are similar to those of other neuropathies, the diagnosis of diabetic neuropathy should be made only after other possible etiologies are excluded (Boulton et al., 2004).
The most common form of diabetic neuropathy is distal symmetric polyneuropathy. It most frequently presents with distal sensory loss. Hyperesthesia, paresthesia, and dysesthesia also occur. Any combination of these symptoms may develop as neuropathy progresses. Symptoms include a sensation of numbness, tingling, sharpness, or burning that begins in the feet and spreads proximally. Neuropathic pain develops in some of these individuals, occasionally preceded by improvement in their glycemic control. Pain typically involves the lower extremities, is usually present at rest, and worsens at night. Both an acute and a chronic form of painful diabetic neuropathy have been described. As diabetic neuropathy progresses, the pain subsides and eventually disappears, but a sensory deficit in the lower extremities persists. Physical examination reveals sensory loss,