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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to study the effects of improved metabolic control on painful diabetic polyneuropathy, 15 patients were treated with continuous subcutaneous insulin infusion over a 12 month period. Polyneuropathy was assessed by pain score, neurological examinations, nerve conduction studies and determination of sensory thresholds and cardiovascular reflexes. Improved metabolic control was confirmed by significantly improved levels of glycosylated haemoglobin (11.7 +/- 0.3% at entry to the study, to 8.7 +/- 0.3% after 12 months; mean +/- SEM). Symptomatic relief was confirmed by significantly improved pain scores. Thresholds for thermal cutaneous sensation improved significantly from 6.0 +/- 0.8 degrees C at entry to the study to 2.7 +/- 0.7 degrees C after 12 months (mean +/- SEM). These findings suggest a selective improvement of peripheral small nerve fibre function after continuous subcutaneous insulin infusion. The importance of quantitating thermal cutaneous sensation in longitudinal studies of patients with diabetic neuropathy was confirmed.
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PMID:Peripheral nerve function in patients with painful diabetic neuropathy treated with continuous subcutaneous insulin infusion. 368 13

Forty-one diabetic patients with symptomatic diabetic neuropathy were studied together with an equal number of matched diabetic subjects without neuropathy. The acetylator status was determined and HLA-A, B, C and DR antigens were investigated. Metabolic control was assessed by measurement of glycosylated haemoglobin and by the mean of multiple random clinic blood glucose values. No significant difference was observed between the two groups in the proportion of fast and slow acetylators. The distribution of HLA frequencies was similar in subjects with and without neuropathy for both Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients. When compared with diabetic subjects without neuropathy, the neuropathy group had higher levels of both glycosylated haemoglobin (mean +/- SEM: 50.1 +/- 1.4 versus 57.5 +/- 1.8 mmol hydroxymethylfurfural/mol haemoglobin (10.5 +/- 0.3 versus 12.0 +/- 0.4% haemoglobin A1, p less than 0.01) mean blood glucose (9.3 +/- 0.4 versus 11.3 +/- 0.5 mmol/l, p less than 0.005). This study provides no evidence that genetic factors increase the susceptibility of diabetic patients to develop neuropathy. In contrast, the elevated glycosylated haemoglobin and blood glucose levels strengthen the association between hyperglycaemia and diabetic neuropathy.
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PMID:Genetic and metabolic studies in diabetic neuropathy. 670 42

Glucagon release during insulin hypoglycemia was studied in diabetics with autonomic neuropathy (N = 9), diabetics without clinical neuropathy (N =8), and normals (N = 9). With similar hypoglycemic stimulus, growth hormone and plasma cortisol increased in all groups. Plasma glucagon increased threefold in normals (121 +/- 19 vs. 308 +/- 30 pg/ml., mean +/- SEM of baseline vs. hypoglycemic peak) and twofold in nonneuropathic diabetics (128 +/- 13 vs. 209 +/- 30). There was no glucagon rise during hypoglycemia in the neuropathic diabetics (128 +/- 23 vs. 115 +/- 20). Arginine infusion produced glucagon rise in the neuropathic diabetics (106 +/- 16 vs. 523 +/- 103). The study suggests that failure to release glucagon during hypoglycemia is due to diabetic neuropathy. Neuropathy may contribute to metabolic instability.
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PMID:Glucagon response to hypoglycemia in diabetic neuropathy. 692 83

1. In the feet of patients with diabetic neuropathy, total skin blood flow is increased due to an increased shunt flow. The question is, does this increased anastomotic shunt flow lead to either under- or overperfused nutritive capillaries. 2. To solve this question, skin microcirculation tests of the left big toe were performed in 20 healthy control subjects and in 40 insulin-dependent diabetic patients without macroangiopathy, 20 without and 20 with neuropathy. Skin temperature measurements and laser Doppler fluxmetry were performed to record mainly shunt flow and capillaroscopy to study nailfold capillary blood flow. 3. The insulin-dependent diabetic patients with neuropathy had a higher baseline skin temperature (mean +/- SEM; 30.0 +/- 0.6 degrees C) and laser Doppler fluxmetry [26.2 +/- 2.2 perfusion units (pu)] than patients without neuropathy (27.2 +/- 0.8 degrees C, P < 0.01; 16.1 +/- 2.0 pu, P < 0.01) and healthy control subjects (27.9 +/- 0.7 degrees C, P < 0.05; 18.6 +/- 2.8 pu, P < 0.05). Sympathetic stimulation (inspiratory gasp) resulted in a smaller laser Doppler fluxmetry decrease in the neuropathic patients (31.4 +/- 4.6%) compared with non-neuropathic patients (48.2 +/- 5.1%, P < 0.05) and control subjects (49.0 +/- 3.8%, P < 0.05), while no difference between the three groups was seen in the laser Doppler fluxmetry decrease during a postural vasoconstriction test. The number of visible capillaries was highest in the neuropathic patients (10.2 +/- 0.6/0.5 mm2), when compared with non-neuropathic patients (8.7 +/- 1.2/0.5 mm2, P < 0.05) and control subjects (8.3 +/- 0.3/0.5 mm2, P < 0.001). Capillary blood-cell velocity was significantly higher in the neuropathic patients (0.32 +/- 0.05 mm/s) compared with non-neuropathic patients (0.23 +/- 0.03 mm/s, P < 0.05) and control subjects (0.23 +/- 0.02 mm/s, P < 0.01). 4. We conclude that there is an overperfused nutritive capillary circulation in the feet of patients with diabetic neuropathy. This is in contradiction to the capillary steal phenomenon and favours the hyperdynamic hypothesis to explain the decreased healing potential in diabetic neuropathic foot ulceration.
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PMID:Skin microcirculation of the foot in diabetic neuropathy. 894 94

Nerve growth factor (NGF) is reduced in epidermal keratinocytes in human diabetic skin, and this decrease has been related to dysfunction of cutaneous sensory fibres. In vitro studies show that keratinocytes express both NGF and its high-affinity receptor, trkA, and that NGF may increase keratinocyte proliferation and its own expression via an autocrine loop. However, the level of trkA expression in vivo by keratinocytes in normal and diabetic skin is unknown. We have therefore measured trkA expression in calf skin biopsies from patients with early subclinical diabetic neuropathy and control subjects, using in situ hybridisation combined with image analysis quantification. Expression of trkC was also studied, as its endogenous ligand neurotrophin-3 (NT-3) is related to NGF, and is present in human epidermis. Hybridisation signal was seen for both trkA and trkC localised throughout the epidermal layer of control skin, with a higher density of silver grain deposition observed for trkA mRNA. However, in diabetic epidermis there was a significant increase (P < 0.001) for both trk A (control, 0.178 +/- 0.013; diabetic, 0.304 +/- 0.032; mean silver grain counts/microm2 +/- SEM) and trkC expression (controls, 0.059 +/- 0.004; diabetics, 0.191 +/- 0.010). The up-regulation of epidermal trk receptors may result from decreased autocrine neurotrophin action, and could represent a compensatory mechanism.
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PMID:trkA and trkC expression is increased in human diabetic skin. 919 81

In order to assess the relationship between chronic painful diabetic neuropathy and current--or lifetime--smoking habits, the smoking history of 49 diabetic patients was investigated and compared with that of 23 diabetic patients without chronic pain (age 51.0 +/- 1.9 years, mean +/- SEM). Current level of nicotine intake was measured using urinary cotinine (a nicotine metabolite), and expressed as cotinine/creatinine ratio (COT/Cr), and lifetime smoking load by pack years (20 cigarettes per day for 1 year equals 1 pack year). Current pain intensity was evaluated using a visual analogue scale (VAS). The presence of chronic painful diabetic neuropathy was based on clinical history and examination. Of those patients with painful neuropathy, 26% were current smokers (age 54.2 +/- 3.2 years, mean +/- SEM), 31% ex-smokers (age 57.0 +/- 2.9 years), and 43% lifelong nonsmokers (age 58.0 +/- 2.9 years). Pain duration and intensity were similar in all three groups. COT/Cr levels were similar in current diabetic smokers with pain [5.0 (0.2-10.6) micrograms/mg] and the diabetic control group of smokers without pain [6.8 (1.8-13.3) micrograms/mg, NS]. There was no relationship between VAS and either COT/Cr levels or pack years in current smokers, or between duration of pain and pack years in diabetic current or ex-smokers. In conclusion, we found no relationship between current or previous levels of smoking and severity or duration of chronic painful diabetic neuropathy.
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PMID:Smoking habits and painful diabetic neuropathy. 936 74

Neurotrophin-3 (NT-3), a member of the neurotrophin family, has been shown to be necessary for the development of muscle spindle and Merkel cell afferent nerve fibres in animal models. The presence of NT-3 in the suprabasal epidermis, where many unmyelinated sensory fibres terminate, has been shown for the first time. As these fibres are affected in early diabetic neuropathy and a clinical trial of recombinant human NT-3 in diabetic neuropathy is in progress, the concentrations of endogenous NT-3 in skin of 24 patients at different stages of diabetic polyneuropathy have been investigated. NT-3 concentrations, measured with a specific immunoassay, were significantly higher in affected skin biopsies from patients with diabetic neuropathy than matched control skin (diabetic skin 6.32 (1.18) pg/mg v control skin 1.28 (0.05) (mean (SEM)); p<0.004, Mann-Whitney U test), particularly in the later stages. The optical density of NT-3-immunostaining was also significantly greater in the epidermis in diabetic patients (diabetic epidermis 0.30 (0.06) v controls 0.24 (0.01); p<0.02). No correlation was found between individual quantitative sensory tests and the increase of NT-3 concentration. The increase of NT-3 seems to reflect the degree of skin denervation in diabetic neuropathy, and may represent a compensatory mechanism. The concentrations of NT-3 in other peripheral targets deserve study in diabetic neuropathy.
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PMID:Neurotrophin-3 is increased in skin in human diabetic neuropathy. 972 60

Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. The experiments were performed in control rats and streptozotocin-diabetic rats fed standard or 1% T-supplemented diets for 6 weeks. All measurements were performed in the sciatic nerve. Malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HA) were quantified with N-methyl-2-phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse-phase HPLC, and NGF by ELISA. MDA plus 4-HA concentration (mean +/- SEM) was increased in diabetic rats (0.127 +/- 0.006 vs 0.053 +/- 0.003 micromol/g in controls, P < 0.01), and this increase was partially prevented by T (0.096 +/- 0.004, P < 0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSSG levels were similar in control and diabetic rats but were lower in diabetic rats treated with T (P < 0.05 vs controls). AA levels were decreased in diabetic rats (0.133 +/- 0.015 vs 0.219 +/- 0.023 micromol/g in controls, P < 0.05), and this deficit was prevented by T. DHAA/AA ratio was increased in diabetic rats vs controls (P < 0.05), and this increase was prevented by T. T levels were decreased in diabetic rats (2.7 +/- 0.16 vs 3.8 +/- 0.1 micromol/g in controls, P < 0.05) and were repleted by T supplementation (4.2 +/- 0.3). NGF levels were decreased in diabetic rats (2.35 +/- 0.20 vs 3.57 +/- 0.20 ng/g in controls, P < 0.01), and this decrease was attenuated by T treatment (3.16 +/- 0.28, P < 0.05 vs diabetic group). In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN.
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PMID:Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy. 1168 53