Diabetic neuropathies are the most prevalent chronic complications of diabetes. This heterogeneous group of conditions affects different parts of the nervous system and presents with diverse clinical manifestations. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons: 

1. Diabetic neuropathy is a diagnosis of exclusion. Nondiabetic neuropathies may be present in patients with diabetes and may be treatable by specific measures.

2. A number of treatment options exist for symptomatic diabetic neuropathy.

3. Up to 50% of diabetic peripheral neuropathies may be asymptomatic. If not recognized and if preventive foot care is not implemented, patients are at risk for injuries to their insensate feet.

4. Recognition and treatment of autonomic neuropathy may improve symptoms, reduce sequelae, and improve quality of life.

Among the various forms of diabetic neuropathy, distal symmetric polyneuropathy (DSPN) and diabetic autonomic neuropathies, particularly cardiovascular autonomic neuropathy (CAN), are by far the most studied (1–4). There are several atypical forms of diabetic neuropathy as well (1–4). Patients with prediabetes may also develop neuropathies that are similar to diabetic neuropathies (5–10). Table 1 provides a comprehensive classification scheme for the diabetic neuropathies.

View this table:

Table 1 
Classification for diabetic neuropathies



Due to a lack of treatments that target the underlying nerve damage, prevention is the key component of diabetes care. Screening for symptoms and signs of diabetic neuropathy is also critical in clinical practice, as it may detect the earliest stages of neuropathy, enabling early intervention. Although screening for rarer atypical forms of diabetic neuropathy may be warranted, DSPN and autonomic neuropathy are the most common forms encountered in practice. The strongest available evidence regarding treatment pertains to these forms.

This Position Statement is based on several recent technical reviews, to which the reader is referred for detailed discussion …

/pdf/diabetic-neuropathy-a-position-statement-by-the-american-2213pwegte.pdf

Diabetic Neuropathy: A Position Statement by the American Diabetes Association

Diabetic peripheral neuropathy is a prevalent, disabling disorder. The most common manifestation is distal symmetrical polyneuropathy (DSP), but many patterns of nerve injury can occur. Currently, the only effective treatments are glucose control and pain management. While glucose control substantially decreases the development of neuropathy in those with type 1 diabetes, the effect is probably much smaller in those with type 2 diabetes. Evidence supports the use of specific anticonvulsants and antidepressants for pain management in patients with diabetic peripheral neuropathy. However, the lack of disease-modifying therapies for diabetic DSP makes the identification of new modifiable risk factors essential. Growing evidence supports an association between components of the metabolic syndrome, including prediabetes, and neuropathy. Studies are needed to further explore this association, which has implications for the development of new treatments for this common disorder.

/pdf/diabetic-neuropathy-clinical-manifestations-and-current-4johxrwimw.pdf

Diabetic neuropathy: clinical manifestations and current treatments

In patients with diabetes, nerve injury is a common complication that leads to chronic pain, numbness and substantial loss of quality of life. Good glycemic control can decrease the incidence of diabetic neuropathy, but more than half of all patients with diabetes still develop this complication. There is no approved treatment to prevent or halt diabetic neuropathy, and only symptomatic pain therapies, with variable efficacy, are available. New insights into the mechanisms leading to the development of diabetic neuropathy continue to point to systemic and cellular imbalances in metabolites of glucose and lipids. In the PNS, sensory neurons, Schwann cells and the microvascular endothelium are vulnerable to oxidative and inflammatory stress in the presence of these altered metabolic substrates. This Review discusses the emerging cellular mechanisms that are activated in the diabetic milieu of hyperglycemia, dyslipidemia and impaired insulin signaling. We highlight the pathways to cellular injury, thereby identifying promising therapeutic targets, including mitochondrial function and inflammation.

Diabetic neuropathy: cellular mechanisms as therapeutic targets.

We report the first nationwide survey of the impact of neuropathic pain, as opposed to nonneuropathic pain, on quality of life and health care utilization in the French general population. A postal questionnaire was sent to a representative sample of 4554 respondents from an initial nationwide survey of 30,155 subjects with or without chronic pain. It included pain characteristics (Neuropathic Pain Symptom Inventory, DN4), quality of life (Medical Outcomes Short Form 12, SF-12), sleep, anxiety/depressive symptoms (Hospital Anxiety and Depression Scale) and health care utilization. In total, 3899 (85.6%) questionnaires were returned, 3816 (97.9%) could be assessed and 3165 subjects (82.9%) confirmed their pain status. Subjects reporting pain and neuropathic characteristics based on the DN4 displayed a higher degree of impairment of all dimensions relating to quality of life and sleep and had higher anxiety/depression scores than those reporting pain without neuropathic characteristics and those without pain (P<.01). They also made greater use of health care facilities, particularly as concerned neurological treatments and visits to neurologists (21% vs 9%; P<.01). Multivariate analyses showed that the neuropathic characteristics of pain made an independent contribution to quality-of-life impairment (P<.0001 and P=.0005 for the physical and mental scores of the SF-12 respectively). Our study indicates that the disease burden of chronic pain depends on the nature of the pain, independently of its intensity and duration.

The specific disease burden of neuropathic pain: results of a French nationwide survey.

Diabetic peripheral neuropathy eventually affects nearly 50% of adults with diabetes during their lifetime and is associated with substantial morbidity including pain, foot ulcers, and lower limb amputation. This review summarizes the epidemiology, risk factors, and management of diabetic peripheral neuropathy and related lower extremity complications. The prevalence of peripheral neuropathy is estimated to be between 6 and 51% among adults with diabetes depending on age, duration of diabetes, glucose control, and type 1 versus type 2 diabetes. The clinical manifestations are variable, ranging from asymptomatic to painful neuropathic symptoms. Because of the risk of foot ulcer (25%) and amputation associated with diabetic peripheral neuropathy, aggressive screening and treatment in the form of glycemic control, regular foot exams, and pain management are important. There is an emerging focus on lifestyle interventions including weight loss and physical activity as well. The American Diabetes Association has issued multiple recommendation statements pertaining to diabetic neuropathies and the care of the diabetic foot. Given that approximately 50% of adults with diabetes will be affected by peripheral neuropathy in their lifetime, more diligent screening and management are important to reduce the complications and health care burden associated with the disease.

Epidemiology of Peripheral Neuropathy and Lower Extremity Disease in Diabetes.

Prevalence and impact on quality of life of peripheral neuropathy with or without neuropathic pain in type 1 and type 2 diabetic patients attending hospital outpatients clinics

https://www.internationaljournalofcardiology.com/article/S0167-5273(05)01248-9/pdf

K. Matthys

Papers

Prevalence and impact on quality of life of peripheral neuropathy with or without neuropathic pain in type 1 and type 2 diabetic patients attending hospital outpatients clinics

Coronary risk factors and inflammation in patients with coronary artery disease and internal cardioverter defibrillator implants

Intensive lipid-lowering therapy and ventricular arrhythmias in patients with coronary artery disease and internal cardioverter defibrillator implants

260 prevalence of polyneuropathy with or without neuropathic pain in type 1 and 2 diabetic patients