Diabetic neuropathy is a most common and troublesome complication of diabetes mellitus, leading to the greatest morbidity and mortality and resulting in a huge economic burden for diabetes care [1,2]. It is the most common form of neuropathy in the developed countries of the world, accounts for more admission to hospital than all the other diabetic complications combined and is responsible for 50±75 % of non-traumatic amputations [2,3]. Diabetic neuropathy is a set of clinical syndromes that affect distinct regions of the nervous system, singly or combined. It can be silent and go undetected, while exercising its ravages, or be present with clinical symptoms and signs that although non-specific and insidious with slow progression also mimic those seen in many other diseases. It is, therefore, diagnosed by exclusion.Diabetic neuropathy is a heterogeneous disorder that encompasses a wide range of abnormalities affecting proximal and distal peripheral sensory and motor nerves as well as the autonomic nervous systems. For these reasons, it has been difficult to obtain precise estimates of the true prevalence and reports vary from 10 to 90 % in diabetic patients, depending on the criteria and methods used to define neuropathy [1±5]. From patients attending a diabetes clinic 25 % reported symptoms; 50 % were found to have neuropathy after a simple clinical test such as the ankle jerk or vibration perception test; almost 90 % tested positive to sophisticated tests of autonomic function or peripheral sensation [6]. Neurologic complications occur equally in Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus and additionally in various forms of acquired diabetes [5]. The major morbidity associated with somatic neuropathy is foot ulceration, the precursor of gangrene and limb loss. Neuropathy increases the risk of amputation 1.7-fold; 12-fold, if there is deformity (itself a consequence of neuropathy), and 36-fold, if there is a history of previous ulceration [7]. There are 65,000 amputations in the United States each year, one every 10 min, and neuropathy is considered to be the major contributor in 87 % of cases. It is also the most life-spoiling of the diabetic complications and has tremendous ramifications for the quality of life of the person with diabetes. Once autonomic neuropathy sets in, life can become quite dismal and the mortality rate approximates 25±50 % within 5±10 years [8,9]. In this review we present and discuss the most recent approaches to the diagnosis and treatment of diabetic neuropathy and the prospects on the horizon. ClassificationDiabetic neuropathy is not a single entity but a number of different syndromes, ranging from subclinical to clinical manifestations depending on the classes of nerve fibres involved. According to the San Antonio Convention [10], the main groups of neurologic disturbance in diabetes mellitus include: (1) subclinical neuropathy, determined by abnormalities in electrodiagnostic and quantitative sensory testing, (2) dif- Diabetologia (2000) 43:...

Diabetic neuropathy is a common complication of diabetes that may be associated both with considerable morbidity (painful polyneuropathy, neuropathic ulceration) and mortality (autonomic neuropathy). The epidemiology and natural history of diabetic neuropathy is clouded with uncertainty, largely caused by confusion in the definition and measurement of this disorder. We have reviewed various clinical manifestations associated with somatic and autonomic neuropathy, and we herein discuss current views related to the management of the various abnormalities. Although unproven, the best evidence suggests that near-normal control of blood glucose in the early years after diabetes onset may help delay the development of clinically significant nerve impairment. Intensive therapy to achieve normalization of blood glucose also may lead to reversibility of early diabetic neuropathy, but again, this is unproven. Our ability to manage successfully the many different manifestations of diabetic neuropathy depends ultimately on our success in uncovering the pathogenic processes underlying this disorder. The recent resurgence of interest in the vascular hypothesis, for example, has opened up new avenues of investigation for therapeutic intervention. Paralleling our increased understanding of the pathogenesis of diabetic neuropathy, refinements must be made in our ability to measure quantitatively the different types of defects that occur in this disorder. These tests must be validated and standardized to allow comparability between studies and more meaningful interpretation of study results.

Patterns of peripheral vasomotion are clearly disordered in diabetes. The loss of low-frequency oscillations observed here suggests a peripheral vascular abnormality that extends past the capillary network to arterial vessels. It is uncertain whether the accompanying small unmyelinated nerve C-fiber dysfunction is a cause or consequence of the impaired microvascular function. Measurement of vasomotion may prove useful as a novel test for peripheral neurovascular function.

To determine the diagnostic value of various cutaneous sensory modalities in diabetic neuropathy, we studied cutaneous perception at the dominant hallux of 113 subjects (32 normal healthy controls and 81 diabetic subjects). The cutaneous sensory perception tests included warm and cold thermal perception, vibration, touch-pressure sensation, and current perception testing (CPT). The sensitivity of each modality when specificity is held greater than 90% was as follows: warm = 78%, cold = 77%, vibration = 88%, tactile-pressure = 77%, 5-Hz CPT = 52%, 250-Hz CPT = 48%, and 2000-Hz CPT = 56%. Combination thermal and vibratory gave optimum sensitivity (92-95%) and specificity (77-86%). We conclude that vibratory and thermal testing should be the primary screening tests for diabetic peripheral neuropathy. Other modalities may be of use only in specific situations.

The purpose of this study was to determine whether peripheral neuropathy explains the apparent association between diabetes and disability in old age, and to evaluate the utility of lower extremity function tests in older diabetic adults with and without neuropathy. We evaluated 39 adults, aged 70-79 years, for pressure sensation (log(10)g), vibration perception threshold (VPT; microns), and electrophysiologic function of the peroneal nerve. The subjects included patients with established diabetic neuropathy (DN; n = 14), diabetic controls without neuropathy (DC; n = 13), and nondiabetic controls (NDC; n = 12). Nonparametric statistical methods were used to relate neuropathy measures to performance in tests of walking speed, static and dynamic balance, coordination, and ankle strength (kilograms). Significant age-adjusted correlations were observed between measures of sensory neuropathy and a variety of performance measures, and electrophysiologic measures were related to static balance. DN subjects had significantly higher pressure sensation than NDC (5.17 vs 3.38g, P < 0.05), higher VPT (62.5 vs 21.7 microm, P < 0.05), and lower peroneal motor response amplitudes at multiple sites. Pressure sensation and nerve conduction measures did not differ between DC and NDC. Compared with NDC, DN subjects performed significantly worse on tests of walking speed (0.99 vs 1.34 m/s; P < 0.05), static balance (4.9 vs 20.4 s; P < 0.05), dynamic balance (9.23 vs 25.52 s; P < 0.05), and coordination (6.73 vs 4.76 s; P < 0.05). No differences were observed in these measures between DC and NDC. Observed differences in physical abilities between older diabetic and nondiabetic adults may have been due to the subset of diabetic individuals with peripheral neuropathy. Quantitative measures of sensory and motor nerve function have distinct effects on physical performance. Interventions aimed at reducing the impact of diabetes-associated disability in old age may have the greatest impact among people with peripheral neuropathy.