However, the epidemiology of the diabetic neuropathies has been difficult to establish with precision because the criteria for diagnoses vary, epidemiologic studies are limited to patients receiving medical care, and diabetes remains undiagnosed in a large population of subjects. Therefore, diabetic neuropathy may be implicated in 50% to 75% of non-traumatic amputations of lower limbs.
However, the epidemiology of the diabetic neuropathies has been difficult to establish with precision because the criteria for diagnoses vary, epidemiologic studies are limited to patients receiving medical care, and diabetes remains undiagnosed in a large population of subjects. Therefore, diabetic neuropathy may be implicated in 50% to 75% of non-traumatic amputations of lower limbs.
Neuropathic pain is defined by the International Association for the Study of Pain as “pain initiated or caused by a primary lesion or dysfunction of the nervous system”.1 Neuropathic pain can be thought of as pain that arises from abnormal nervous system physiology with diverse clinical manifestations and can affect virtually every tissue of the body.Members of an International Consensus agreed on a simple definition of diabetic neuropathy as the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes.
Approximately 10% of peripheral neuropathy in diabetes appears to be of non-diabetic etiology. For this reason, it is very important to conduct a careful clinical examination and always consider that absence of symptoms must never be equated with absence of neuropathy.
Several randomized controlled clinical trials completed over recent years have demonstrated the effect of improved glycemic control on microvascular and neurological complications of diabetes. Among the most representative in type 1 diabetes is the Diabetes Control and Complications Trial (DCCT) trial and the most representative in type 2 diabetes is the UK Prospective Diabetes Study (UKPDS).The DCCT shows us that the intensive treatment group achieved a median glycosylated hemoglobin (Hb) A1C of 7.2% during a mean follow-up of 6.5 years and a dramatic 64% reduction for confirmed clinical neuropathy. The UKPDS failed to support a similar correlation between incidence of neuropathy and glycemic control in type 2 diabetes patients, but the progression of diabetic neuropathy is dependent on glycemic control. In one of the largest trials to date, the Rochester Diabetic Neuropathy Cohort, two-thirds of patients had type 1 diabetes and one-third type 2 diabetes. Peripheral neuropathy of some type was found by objective testing in 66% of patients with type 2 diabetes, though only 15% had symptoms at the moment of clinical assessment.The diabetic neuropathies comprise several different clinical syndromes that may occur in isolation or in varying combinations. In this study, distal symmetric polyneuropathy was the must common neuropathy in type 2 diabetes, affecting 54% of patients, and only 13% were symptomatic.Median mononeuropathy at the wrist (carpal tunnel syndrome) was second, affecting 33%.
Current understanding of the pathophysiology is complicated and incomplete, but recently numerous competing and/or pathological pathways have begun to intersect and complement each other opening the future development of new potential therapeutic targets (see Figure 1).The biochemical alterations that have been studied more are the formation of advanced glycation end-products, oxidant stress, the polyol pathway, and protein kinase C (PKC).
Recently, endothelial function has gained increasing attention in understanding vascular health and disease.The endothelium plays a vital role in vascular homeostasis, regulating vascular tone, vascular smooth muscle cell (VSMC) proliferation, transendothelial leukocyte migration, and thrombolysis. Endothelial dysfunction has also been considered an important event in the development of diabetic neuropathy.
Diagnosis
No single test can demonstrate that the primary cause of nerve injury is diabetes. Consequently, diabetic neuropathy is both a clinical diagnosis and a diagnosis of exclusion.A careful history and physical examination are critical and often reveal patterns conforming to a single known diabetic syndrome or some combination of the known syndromes (see Table 1).
The possibility that the diabetic patient may also develop a neuropathy from a cause other than diabetes is always present. On the other hand, in patients with neuropathy but no previous diagnosis of diabetes, a glucose tolerance test may be useful to exclude diabetes (see Table 2).
The diagnosis of the various forms of neuropathy requires awareness of the differing manifestations of these abnormalities, with sensory neuropathy causing numbness as a late manifestation and excessive function with prickling, stabbing, or burning symptoms characteristically seen earlier. Motor neuropathy leads to wasting and weakness, typically found late in the clinical course and usually less severe as clinical manifestations than the sensory abnormalities (see Table 3).
Chronic Sensorimotor Neuropathy
Chronic sensorimotor neuropathy is the most common presentation of neuropathy in diabetes; up to 50% of patients may experience symptoms, most frequently burning pain, electrical or stabbing sensations, paresthesia, hyperesthesia, and deep aching pain (see Table 4). Many patients are asymptomatic, and a neurological deficit may be discovered during a routine neurological clinical examination.
Acute Sensory Neuropathy
Acute sensory neuropathy is rare, tends to follow periods of poor metabolic control or sudden changes, and is characterized by the acute onset of severe sensory symptoms (see Table 4).
