Diabetic neuropathies

Abstract

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:...

Evidence of Nerve Conduction Defects in Type-II Diabetic Patients without Neuropathic Symptoms

“…Severe decline in conduction velocity is most often detected in sural nerve. This is in accordance with the well-known fact that DPN mostly involves lower limb sensory nerves 19 . Relating to the conduction velocities of motor nerves, the statistically significant difference between asymptomatic and symptomatic groups is observed for median nerve in the upper limb with a 'p' value of <0.05 and peroneal nerve in the lower limb with a 'p' value of 0.025.…”

Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathy

“…The polyol pathway is thought to play a major metabolic role in the development of diabetic neuropathy (Greene & Sima, 1992;Sima & Sugimoto, 1999;Zochodne, 1999;Vinik, Pittenger, McNitt, & Stansberry, 2000). Persistent hyperglycemia increases the polyol pathway activity in conjunction with accumulation of sorbitol and fructose in nerves, and this is accompanied by a reduction in myo-inositol uptake and inhibition of Na + /K + -ATPase, resulting in Na + retention, edema, myelin swelling, axoglial disjunction, and nerve degeneration (Greene, Lattimer, & Sima, 1987;Vinik, Pittenger, McNitt, & Stansberry, 2000).…”

“…Persistent hyperglycemia increases the polyol pathway activity in conjunction with accumulation of sorbitol and fructose in nerves, and this is accompanied by a reduction in myo-inositol uptake and inhibition of Na + /K + -ATPase, resulting in Na + retention, edema, myelin swelling, axoglial disjunction, and nerve degeneration (Greene, Lattimer, & Sima, 1987;Vinik, Pittenger, McNitt, & Stansberry, 2000). Moreover, an increase in the activity of aldose reductase, an enzyme that catalyzes the reduction of glucose to sorbitol in the first step of the polyol pathway, may compete with nitric oxide synthase for NADPH, resulting in a reduction in nitric oxide.…”

Non-Enzymatic Glycosylation and Deglycating Enzymes

“…Diabetes mellitus is a major cause of peripheral neuropathy, manifested as distal symmetrical polyneuropathy (62). Basement membrane thickening and pericyte degeneration have been observed in diabetic neuropathy.…”