The role of endoneural edema in the pathogenesis of diabetic neuropathy

Average endoneurial area was correlated with measurements of myelinated fiber density in sural nerves from diabetics and controls. Although, in general, myelinated fiber density decreased with increasing endoneurial area, this relationship was not significant for diabetic nerves. The increase in endoneurial area was attributed to expansion of the endoneurial space as a result of endoneurial edema. A possible role for such edema in the pathogenesis of diabetic neuropathy is considered.     

糖网病发病机理的研究进展

糖尿病视网膜病变是致盲的常见原因 ,因而最引人注意。多年来 ,国内外学者对糖网病进行了大量实验性和应用性研究 ,取得了一定的进展。本文在简要回顾糖网病病理变化的基础上 ,对其发病机制 ,诸如高血糖与糖网病、糖网病与糖代谢异常的学说以及血管生成因子的作用等作一综述。     

Morphology of diabetic neuropathy

The morphological findings in peripheral nerves in diabetic subjects are reviewed. Diabetes is probably the most frequent cause of neuropathy. However it does not constitute a single nosological entity but is comprised of a variety of clinical and morphological changes. These are considered to be the consequences of metabolic derangements resulting from chronic hyperglycemia. Distal symmetrical neuropathies, which are most common, are characterized by axonal degeneration and segmental demyelination with loss of nerve fibres and fibrosis. Remyelination and axonal sprouting occur. Microvascular changes consist of thickening and hyalinization of the walls of the vessels. On electron microscopy these vessels appear thickened and show reduplication of the basal lamina that surrounds the endothelial cells and pericytes. The morphological bases of proximal symmetrical motor neuropathy, as well as of focal and multifocal neuropathies are briefly described. The synopsis of current knowledge can be helpful in diagnosis and differential diagnosis of disorders of the peripheral nervous system.     

Experimental diabetic autonomic neuropathy.

The regular occurrence of autonomic neuropathy, colonic dilatation, and loss of fecal consistency was investigated in streptozotocin-diabetic, age-matched control, and pancreatic-islet--transplanted rats using ultrastructural, histochemical, and biochemical methods. Degenerating unmyelinated axons were observed by electron microscopy in the colonic submucosa and muscularis, ileal mesentery, and splenic pedicle in 5--7 months diabetic animals; similar changes were not found in control rats or animals subjected to islet transplantation three weeks after induction of diabetes and sacrificed 4--6 months later (colon only). Regenerative changes, including axons with identifiable growth cones, were demonstrated in the mesenteric nerves of chronically diabetic animals. Formaldehyde-induced catecholamine fluorescence and cholinesterase histochemistry suggested deficiencies in colonic adrenergic and cholinergic innervation; histochemical findings in islet-transplanted animals were comparable to those of untreated control animals. Biochemical measurements of the adrenergic and cholinergic nervous system marker enzymes dopamine-beta-hydroxylase and choline acetyltransferase, respectively, in colon and spleen confirm a deficit in adrenergic (colon and spleen) and cholinergic (colon) innervation in chronically diabetic animals.     

Pro-nociceptive role of the activation of mineralocorticoid receptor in the pathogenesis of painful diabetic neuropathy

Patients with diabetic neuropathy may develop severe pain which persists over several years, resulting from impaired nerve endings in the skin, which originate the pain signals of diabetic neuropathy. Inflammatory processes have been implicated in the genesis and maintenance of chronic pain. The activation of the mineralocorticoid receptor (MR) is believed to promote classical inflammation features such as high levels of oxidative metabolites and proinflammatory cytokines, tissue destruction. Selectively blocking MR’s can prevent the development of pain behaviors induced by neuroinflammation. Since proinflammatory cytokines and mediators were found to have increased in diabetic skin, we propose MR activation may play a pro-nociceptive role in diabetic neuropathy through local inflammation of the skin. Research methods examining MR overexpression in normal skin and selectively blocking MR in the diabetic skin are useful in identifying whether MR activation may bring cutaneous nerve insult and to explain whether MR activation is involved in the progression of painful diabetic neuropathy. If proven, this hypothesis would indicate the MR may potentially act as a novel target for pain therapeutics.     

Electrodiagnostic criteria in CIDP: comparison with diabetic neuropathy

This study examines current criteria for CIDP by comparing the electrodiagnostic data from 17 patients who have biopsy proven CIDP with 29 patients with diabetic neuropathy. The groups were comparable in age. Data were examined using four sets of published criteria for primary demyelination. Two sets (A & B) defined demyelination based on distal motor latencies, F-wave latencies, motor conduction velocities, and temporal dispersion or conduction block. The other two sets defined demyelination based on slowing of motor conduction velocity < 70% of the lower limit of normal (LLN) in either 2 nerves (set C), or in a single nerve (set D). Using set A, 3/17 patients with CIDP met the criteria for a demyelinating neuropathy, while this was true in 2/29 of the patients with diabetic neuropathy. For sets B and C, data consistent with a demyelinating neuropathy were identified in 2/17 and 1/29 patients, respectively. Using set D criteria for demyelination was met in 6/17 of the patients with CIDP and in 5/29 of the diabetic patients. None of the criteria sets showed a significant difference between CIDP and diabetic neuropathy (p = 0.3 to 0.5). Though electrodiagnosis is an important element in the diagnosis of CIDP, current electrodiagnostic criteria alone are insufficient for defining many cases of CIDP.     

Sympathetic skin response in diabetic neuropathy

Sympathetic function test was undertaken using the sympathetic skin response (SSR), a technique for assessment of sudomotor activity, in 67 diabetics, and the results were compared with those from 45 age-matched normal subjects. The SSR was readily elicitable in normal subjects, but absent in six patients with diabetes. In 28 patients, the SSR was preserved, but their amplitude was below the normal range. The decrease in the SSR amplitude correlated well with a fall in motor and sensory conduction velocity. The SSR magnitude correlated well to the impaired R-R interval variation during deep breathing and the heart rate increase and the blood pressure change on standing, indicating a close correlation between the disturbance of sudomotor function and that of other sympathetic and parasympathetic functions. Most of the patients with clinical evidence of dysautonomia and with insulin treatment revealed diminished or absent SSR.     

Sympathetic skin response in diabetic neuropathy

Autonomic neuropathy is a complication of diabetes mellitus (DM) in substantial proportion of cases and may cause definite autonomic symptoms. Because conventional electrophysiological methods do not assess the autonomic nervous system, simple reproducible tests were developed. One of them is sympathetic skin response (SSR) which provides useful information about the status of sympathetic postganglionic function. The aim of this study is to perform SSR in diabetic patients to see whether this test can be used as an electrophysiological method for the diagnosis and confirmation of diabetic autonomic neuropathy. 20 diabetic patients who had electrophysiologically confirmed polyneuropathy but showed no symptoms or signs referable to autonomic system dysfunction were included. 14 (70%) patients demonstrated abnormal SSR. 2 abnormal patterns were observed. An absent response in at least one tested lower extremity (50%) and prolonged foot with normal hand latency (20%). 6 patients (30%) demonstrated no abnormalities. Foot and hand latencies in diabetics did not differ significantly from those of normal controls (p: 0.4, p: 0.1) and no correlation could be found with latencies and duration of sickness, patient's age and HbA1c values. We believe latency measurement is an objective measure of conduction in multineural pathways and can detect subclinical involvement of sympathetic nervous system in diabetics who do not manifest symptoms or signs referable to autonomic system dysfunction.     

Auditory neuropathy in streptozotocin-induced diabetic mouse

An investigation of the mechanism of damage to the peripheral nervous system and central nervous system in diabetes mellitus (DM) is highly important in current neurological research. Auditory neuropathy is a hearing disorder in which the auditory brainstem evoked potential is absent or severely abnormal. This study investigated auditory neuropathy caused by streptozotocin in mouse model. In order to assess diabetic auditory neuropathy, we evaluated auditory brainstem response (ABR) for the evaluation of sensorineural function in peripheral auditory nerve. Auditory middle latency response (AMLR) was employed to assess the middle response in the midbrain. STZ groups significantly increased the absolute latencies IV and the interpeak latencies I-III and I-IV of ABR compared with STZ 0 group. Pa latency of AMLR also significantly increased in proportion to STZ dosage. Taken together, our results demonstrate that STZ-induced DM may impair the auditory pathway from peripheral auditory nerve to midbrain in the mouse model. We suggest that the STZ-induced diabetic mouse model may be useful for the evaluation of auditory pathway impairment by using ABR and AMLR tests.     

Oral zinc therapy in diabetic neuropathy

The present double blind randomized study was conducted on 50 subjects; 20 age and sex matched healthy controls (Group--I); 15 patients of diabetes mellitus with neuropathy who received placebo for 6 weeks (Group--IIA); and 15 patients of diabetes mellitus with neuropathy who were given supplemental zinc sulphate (660 mg) for 6 weeks (Group--IIB). Serum zinc level, fasting blood sugar (FBS) and post prandial blood sugar (PPBS) levels and motor nerve conduction velocity (MNCV) were estimated on day 0 and after 6 weeks in all subjects. Serum zinc levels were significantly low (p < 0.001) in group IIA and IIB as compared to healthy controls (Group--I) at baseline. After 6 weeks the change in pre and post therapy values of FBS, PPBS and MNCV (median and common peroneal nerve) were highly significant (P = < 0.001) for group IIB alone with insignificant change (P = > 0.05) in group IIA. No improvement (P = > 0.05) in autonomic dysfunction was observed in either groups. Therefore, oral zinc supplementation helps in achieving better glycemic control and improvement in severity of peripheral neuropathy as assessed by MNCV.