Diabetes and Peripheral Nerve Disease.

It is increasingly recognized that diabetic neuropathy is associated with early diabetes, prediabetes, and the metabolic syndrome. Early detection and diagnosis are important to slow progression and prevent complications. Although strict glucose control is an effective treatment in type 1 diabetes, it is less effective in type 2 diabetes. There is a growing body of literature that lifestyle interventions may be able to prevent or slow progression of neuropathy in type 2 diabetes. In addition to the typical distal symmetric polyneuropathy, there are many types of "atypical" diabetic neuropathies that are important to recognize.

Is there cardiac autonomic neuropathy in prediabetes?

Although there is considerably more data showing an association between type 2 diabetes mellitus (T2DM) and autonomic neuropathy, accumulating evidence indicates that cardiovascular autonomic neuropathy (CAN) is common in persons with impaired glucose tolerance (IGT). Furthermore, CAN may occur early after a metabolic insult and obesity, especially among mean, and seems to play an important role in the early pathogenesis of CAN. Autonomic symptoms are common in subjects with IGT. In addition to defects in CAN, in subjects with IGT, there is impaired sudomotor function and abnormalities of endothelial peripheral vasoreactivity. At the present time, the only interventions that may be effective in preventing or reversing IGT associated autonomic neuropathy are lifestyle improvement. These include a tailored diet and exercise program. Other approaches that may be beneficial include modulation of oxidative stress and improvement of metabolic regulation in subjects with IGT. Interventions are most likely to be effective early in the course of disease and therefore it is extremely important to have early diagnosis of IGT and autonomic neuropathy.

Physical activity and dietary interventions in diabetic neuropathy: a systematic review.

PURPOSE: Diabetic neuropathy is a common and disabling disorder, and there are currently no proven effective disease-modifying treatments. Physical activity and dietary interventions in patients with diabetes and diabetic neuropathy have multiple beneficial effects and are generally low risk, which makes lifestyle interventions an attractive treatment option. We reviewed the literature on the effects of physical activity and dietary interventions on length-dependent peripheral neuropathy and cardiac autonomic neuropathy in diabetes. METHODS: The electronic database PubMed was systematically searched for original human and mouse model studies examining the effect of either dietary or physical activity interventions in subjects with diabetes, prediabetes, or metabolic syndrome. RESULTS: Twenty studies are included in this review. Fourteen studies were human studies and six were in mice. Studies were generally small with few controlled trials, and there are no widely agreed upon outcome measures. CONCLUSIONS: Recent research indicates that dietary interventions are effective in modifying diabetic neuropathy in animal models, and there are promising data that they may also ameliorate diabetic neuropathy in humans. It has been known for some time that lifestyle interventions can prevent the development of diabetic neuropathy in type 2 diabetes mellitus subjects. However, there is emerging evidence that lifestyle interventions are effective in individuals with established diabetic neuropathy. In addition to the observed clinical value of lifestyle interventions, there is emerging evidence of effects on biochemical pathways that improve muscle function and affect other organ systems, including the peripheral nerve. However, data from randomized controlled trials are needed.

Neuropathic Pain.

PURPOSE OF REVIEW: Neuropathic pain is a frequently encountered condition that is often resistant to treatment and is associated with poor patient satisfaction of their treatment. Several medications have been shown to be effective in treating neuropathic pain associated with diabetic neuropathy and postherpetic neuralgia, and these medications are often used to treat neuropathic pain associated with other conditions as well. This article summarizes the diagnosis and assessment of patients with neuropathic pain as well as available pharmacologic and interventional treatment options. RECENT FINDINGS: Evidence-based recommendations for the treatment of neuropathic pain have been published, and first-line medications include antidepressants, anticonvulsants, topical agents, as well as opioid analgesics. Interventional options include anesthetic and steroid injections, nerve blocks, and spinal cord stimulation. Essential to the treatment algorithm of neuropathic pain is the assessment and treatment of psychosocial comorbidities and the utilization of a multidisciplinary team approach, including cognitive-behavioral and rehabilitative therapies. Questions remain about the comparative effectiveness of various medications and combination therapies. Increasing interest also exists in the optimization and personalization of pharmacotherapy based upon the underlying mechanism(s) of neuropathic pain according to the quality of the patient's symptoms. SUMMARY: The management of chronic neuropathic pain is challenging and is best achieved with the use of a multidisciplinary team. Pain is a subjective experience, and it is important to validate a patient's pain, address psychosocial comorbidities, and set realistic treatment goals. Evidence-based guidelines are available to guide treatment, but frequently, high-quality evidence-based recommendations are lacking.

Diabetes and Cognitive Impairment.

Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with reduced performance on multiple domains of cognitive function and with evidence of abnormal structural and functional brain magnetic resonance imaging (MRI). Cognitive deficits may occur at the very earliest stages of diabetes and are further exacerbated by the metabolic syndrome. The duration of diabetes and glycemic control may have an impact on the type and severity of cognitive impairment, but as yet we cannot predict who is at greatest risk of developing cognitive impairment. The pathophysiology of cognitive impairment is multifactorial, although dysfunction in each interconnecting pathway ultimately leads to discordance in metabolic signaling. The pathophysiology includes defects in insulin signaling, autonomic function, neuroinflammatory pathways, mitochondrial (Mt) metabolism, the sirtuin-peroxisome proliferator-activated receptor-gamma co-activator 1α (SIRT-PGC-1α) axis, and Tau signaling. Several promising therapies have been identified in pre-clinical studies, but remain to be validated in clinical trials.

Clinical neuropathy scales in neuropathy associated with impaired glucose tolerance.

AIMS: Disagreement exists on effective and sensitive outcome measures in neuropathy associated with impaired glucose tolerance (IGT). Nerve conduction studies and skin biopsies are costly, invasive and may have their problems with reproducibility and clinical applicability. A clinical measure of neuropathy that has sufficient sensitivity and correlates to invasive measures would enable significant future research. METHODS: Data was collected prospectively on patients with IGT and symptomatic early neuropathy (neuropathy symptoms <2years) and normal controls. The seven scales that were examined were the Neuropathy Impairment Score of the Lower Limb (NIS-LL), Michigan Diabetic Neuropathy Score (MNDS), modified Toronto Clinical Neuropathy Scale (mTCNS), Total Neuropathy Score (Clinical) (TNSc), The Utah Early Neuropathy Scale (UENS), the Early Neuropathy Score (ENS), and the Neuropathy Disability Score (NDS). RESULTS: All seven clinical scales were determined to be excellent in discriminating between patients with neuropathy from controls without neuropathy. The strongest discrimination was seen with the mTCNS. The best sensitivity and specificity for the range of scores obtained, as determined by using receiver operating characteristic curves, was seen for the mTCNS followed by the TNSc. Most scales show a stronger correlation with measures of large rather than small fiber neuropathy. CONCLUSIONS: All seven scales identify patients with neuropathy. For the purpose of screening potential patients for a clinical study, the mTCNS followed by the TNSc would be most helpful to select patients with neuropathy.

Diabetic neuropathies.

PURPOSE OF REVIEW: This article provides an overview for understanding the diagnosis, pathogenesis, and management of diabetic neuropathy. RECENT FINDINGS: New information about the pathogenesis of diabetic neuropathy continues to emerge, which will lead to identifying new drug targets. It is clear that the natural history of diabetic neuropathy is changing and the rate of progression is slowing. This is likely because of a combination of earlier diagnosis, improved glycemic management, and improved control of related complications such as hyperlipidemia and hypertension. Early diagnosis is critical, and small fiber neuropathy or subclinical diabetic neuropathy may be reversed or significantly improved with appropriate intervention. The American Academy of Neurology recently published guidelines for the treatment of painful diabetic neuropathy. SUMMARY: Diabetic neuropathy is common and can present with varied clinical presentations discussed in this article. Although treatment currently focuses on pain management, attention should be paid to potential risk factors for neuropathy. For example, glycemic control, hyperlipidemia, and hypertension should be managed with diet, exercise, and medications. Class I or II clinical studies indicate that pregabalin, duloxetine, amitriptyline, gabapentin, and opioids are effective in the management of diabetic neuropathic pain.