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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic neuropathy is a common and disabling complication of diabetes mellitus whose pathogenesis remains unknown. Insulin-like growth factors (IGFs) have been recently implicated in the development and maintenance of the peripheral nervous system, and circulating IGF levels are decreased in experimental and clinical diabetes. Therefore, we tested the hypothesis that IGF gene expression is reduced in peripheral nerves early after the onset of diabetes. Sciatic nerves from nondiabetic and streptozotocin-treated rats were removed 5-7 days after the induction of diabetes. RNA was isolated and analyzed by Northern and slot blots. IGF-I mRNA content was significantly decreased per milligram wet weight nerve (P < 0.025) as well as per poly(A)+ RNA (P < 0.01) in diabetic vs nondiabetic nerves. Likewise, the amount of IGF-II mRNA was significantly decreased per milligram wet weight nerve (P < 0.01) as well as per poly(A)+ RNA (P < 0.005). These effects were selective because histone 3.3 mRNA content, as well as poly(A)+ mRNA content, per milligram nerve were unchanged. Insulin treatment partially prevented this decline in IGF-I and IGF-II mRNA levels. The diminished IGF mRNA content is one of the earliest biochemical abnormalities to be observed in the diabetic nerve, supporting the hypothesis that a reduction in IGF activity in diabetic nerves precedes and contributes to the development of neuropathy.
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PMID:Early reduction in insulin-like growth factor gene expression in diabetic nerve. 782 85

Diabetic neuropathy is a major complication of diabetes mellitus affecting to an equal extent type 1 and type 2 patients. Various mechanisms including metabolic and vascular abnormalities have been proposed to explain the progressive pathological changes that occur in peripheral nerve. Regardless of the precise mechanisms, structural abnormalities lead to functional changes which eventually result in the clinical manifestations of diabetic neuropathy. Possible interventions that may influence the progressive disease process include intensive insulin therapy and aldose reductase inhibitors. This article reviews the proposed pathogenetic mechanisms underlying diabetic neuropathy, their effects on nerve histomorphometric changes and ultrastructure typical of diabetic neuropathy, and potential therapeutic interventions and their impact on disease progression.
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PMID:Pathological definition and evaluation of diabetic neuropathy and clinical correlations. 787 8

Diabetic polyneuropathy is a complex disease of progressive nerve fiber loss. Initial screening and diagnosis in clinical practice usually depend on assessment of subjective complaints. A need exists for objective, simple, and reproducible assessment tools that can be readily used in clinical practice. The importance of early diagnosis is highlighted by the recent North American Diabetes Control and Complications Trial where intensive insulin therapy reduced the risk of developing diabetic neuropathy by 61%. At the University of Michigan, we have developed an outpatient neuropathy program. Patients are given a questionnaire and a brief screening examination, designated the Neuropathy Screening Instrument. Diabetic neuropathy is confirmed and staged in patients with a positive Neuropathy Screening Instrument, by a quantitative neurologic examination and nerve conduction studies, designated the Diabetic Neuropathy Score. The Michigan program has been compared with well-established instruments and has been found to be sensitive and reproducible for screening and diagnosis. We believe the program provides a valuable tool for the clinician in the practice setting and should allow diagnosis and intervention earlier in the course of diabetic neuropathy.
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PMID:Clinical testing in diabetic peripheral neuropathy. 787 10

To evaluate whether cerebral glucose metabolism is impaired in diabetes the [18F]-2-deoxy-2-fluoro-D-glucose method and positron emission tomography were used to determine the regional cerebral metabolic rate of glucose in 12 healthy subjects, 8 newly diagnosed Type 1 diabetic patients 6 Type 1 diabetic subjects without peripheral neuropathy, and 7 Type 1 diabetic patients with symptomatic peripheral neuropathy, all of whom were men. In addition, multimodal evoked potentials were assessed. Cerebral glucose consumption was significantly reduced in the group with neuropathy as compared with the newly diagnosed diabetic patients and the healthy subjects (26.9 +/- 1.0 vs 33.9 +/- 1.9 and 32.5 +/- 1.1 mumol 100 g-1 min-1; p < 0.05), while in the patients without neuropathy it was 30.2 +/- 2.5 mumol 100 g-1 min-1 (NS vs the remaining groups). There were no significant differences between the groups regarding brainstem auditory and visual evoked potentials. No relationship was noted between cerebral glucose metabolism and P300 latency of event-related potentials as an index of cognitive function, but there was an inverse correlation with age (r = -0.42; p < 0.05) and duration of diabetes (r = -0.67; p < 0.05). These results suggest that cerebral glucose metabolism is normal at the time of diagnosis of Type 1 diabetes, but may become altered with both increasing duration of diabetes and age in the absence of central conduction deficits or cognitive dysfunction. Diabetic neuropathy may constitute a possible additional correlate of reduced cerebral glucose consumption.
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PMID:Cerebral glucose metabolism in type 1 diabetic patients. 820 Feb 8

Diabetic neuropathy (DN) is one of the most frequent and severe long-term complications in elderly diabetes. Most scientists believe that onset of chronic complications in diabetics is due to prolonged glycometabolic imbalance. Recently aldose reductase inhibitors (ARI) have been used in the treatment of DN. We studied 100 elderly subjects affected by diabetes mellitus who were treated with tolrestat, an ARI, for a year and a control group who received a placebo. All subjects underwent the following examinations at the start of treatment and then at 8, 24, 42 and 52 weeks: 1. electromyography of the lower and upper limbs', 2. biotensiometric evaluation of the vibratory perception threshold (VPT), 3. glycosylated hemoglobin, 4. hourly glycemic profile, azotemia, creatininemia, hemochrome, cholesterol, triglycerides, bilirubin, electrolytes, protidogram, urine. The patients on tolrestat showed: increased nerve conduction velocity (mean values 2.3 m/sec) of the ulnar nerve; increased nerve conduction velocity (mean values 3.9 m/sec) of the peroneal nerve; reduced VPT at the right and left first toe (mean values 5 and 7 volts respectively); reduced VPT at the right and left malleoli (mean values 10 and 8 volts respectively). The authors recommend prompt, long term ARI treatment be initiated before the onset of evident signs of neuropathy in elderly subjects.
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PMID:[Treatment with an aldose reductase inhibitor in peripheral neuropathy in elderly diabetic patients]. 824 17

Diabetic neuropathy results from progressive nerve fibre damage with blunted nerve regeneration and repair and may be complicated by nerve hyperexcitability resulting in pain. The naturally occurring amino acid taurine functions as an osmolyte, inhibitory neurotransmitter, and modulator of pain perception. It is also known to have neurotrophic actions. The compatible osmolyte hypothesis proposes that levels of intracellular organic osmolytes including taurine and myo-inositol, respond co-ordinately in response to changes in intracellular sorbitol or external osmolality to maintain the intracellular milieu. We hypothesize that glucose-induced sorbitol accumulation in diabetes mellitus will result in taurine depletion in peripheral nerve which may potentially impair nerve regeneration and precipitate neuronal hyperexcitability and pain. This study explored the relationships of taurine, myo-inositol and sorbitol in the rat nerve and their effects on nerve conduction velocity. Osmolyte levels and nerve conduction velocity were determined in sciatic nerve from non-diabetic and streptozotocin-induced diabetic rats, with or without dietary taurine or myo-inositol supplementation. Taurine levels decreased by 31% (p < 0.01) and myo-inositol decreased by 37% (p < 0.05) in diabetic nerve as sorbitol accumulated. Taurine supplementation of diabetic animals did not affect nerve conduction velocity but further reduced nerve myo-inositol levels. Prevention of sorbitol accumulation with the aldose reductase inhibitor sorbinil increased nerve taurine levels by 22% (p < 0.05) when compared with untreated diabetic animals. Thus, we have demonstrated an interdependence of organic osmolytes within the nerve. Abnormal accumulation of one osmolyte results in reciprocal depletion of others. Diabetic neuropathy may be an example of maladaptive osmoregulation, nerve damage and instability being aggravated by taurine depletion.
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PMID:Osmotically-induced nerve taurine depletion and the compatible osmolyte hypothesis in experimental diabetic neuropathy in the rat. 835 77

Diabetic neuropathy is the most frequent complication of diabetes and the leading cause of polyneuropathy in the Western world. A distal symmetric predominantly sensory polyneuropathy is the most common of the diverse neuropathies that occur secondary to diabetes. Pain is often the most bothersome and difficult to treat symptom of diabetic neuropathy. Autonomic neuropathy is a frequent feature of diabetic neuropathy and the source of many significant problems including postural hypotension, gastroparesis, diarrhea, constipation, neurogenic bladder, and male impotence. Physicians need to be familiar with the multiple, less common forms of diabetic neuropathy, as these often mimic other medical or neurologic conditions. The cause of diabetic neuropathy is not determined, but abundant evidence suggests that both metabolic and ischemic nerve injury are likely factors. These should not be considered mutually exclusive causes of diabetic neuropathy as both factors likely operate to different degrees to produce the clinical spectrum of neuropathies that are seen in diabetes. Although no effective treatment exists to cure diabetic neuropathy, improvement is possible with glycemic control and symptomatic therapy.
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PMID:Neuropathies associated with diabetes. 841 16

Diabetic neuropathy affects both sensory and autonomic peripheral nerve fibres. Vasoactive intestinal polypeptide (VIP) is present in autonomic fibres which modulate sweat secretion, while calcitonin gene-related peptide (CGRP) is localized to cutaneous sensory fibres. In this study, immunohistochemistry and image analysis were used to assess changes of VIP and CGRP, and of the pan-neuronal marker protein gene-product (PGP)-9.5, in skin biopsies of 18 patients affected by type 1 diabetes (age range 18-46 years) and from seven aged-matched controls. Patients were divided into three groups: group 1 (n = 6), with diabetes for 6 months to 3 years; group 2 (n = 5), with the disease for 5-10 years; and group 3 (n = 7), with diabetes for more than 10 years. VIP immunoreactivity (IR) and PGP-9.5-IR were significantly reduced around sweat glands (P < 0.005) in groups 2 and 3. Epidermal CGRP-IR and PGP-9.5-IR were significantly reduced in group 3 (P < 0.05). Twenty-eight per cent (5/18) of all patients showed high VIP-IR around sweat glands (> 95 per cent confidence limits of controls) and all of these patients had diabetes for less than 3 years. Conversely, 55 per cent (10/18) of patients had low VIP-IR (< 5 per cent confidence limit of controls). The latter, compared with the former, showed a significantly longer duration of diabetes (Fisher exact test P = 0.002), presence of clinical autonomic neuropathy (Fisher exact test P = 0.04), and a reduced sural nerve conduction velocity (Fisher exact test P = 0.04). These results suggest that quantitative immunohistochemical analysis of peptide-containing cutaneous nerves allows an objective evaluation of nerve fibre alterations at early stages of diabetes than is currently possible with neurophysiological functional tests.
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PMID:Early increase precedes a depletion of VIP and PGP-9.5 in the skin of insulin-dependent diabetics--correlation between quantitative immunohistochemistry and clinical assessment of peripheral neuropathy. 844 92

Diabetic neuropathy may cause an alteration of the function of the muscles of the sole of the foot. This is at the origin of the chronic dislocation of the articular heads, mainly of the little metatarsal bones (neuro diabetes arthropathy), with formation of areas of pathological pressure. The tissues below being chronically under pressure are affected by trophic lesions called "plantar perforating disease". Recovery may be obtained by not exposing the injured area of the foot to pressure and through careful local therapy. This doesn't prevent disease from appearing again, even though some specially conceived soles are being used, aiming at a correct weight redistribution on the sole of the foot. The clinical case we are describing applies to a man affected by insulin dependent diabetes mellitus, with relapsing diabetic foot ulcers, in spite of him using a specifically designed sole. Such lesion is aggravated by a serious infection which, by gradually penetrating in depth, leads to osteomyelitis, affecting the 5th Metatarsal head. The bone area, dislocated by neuroarthropathy, was presumably responsible for the persisting plantar lesion. The amputation of this infected necrotic structure, has led to the overcoming of the serious septic problem. By eliminating the bone link responsible for the transmission of the pathological pressure, the plantar lesion the patient had been suffering from for a long time, has consequently disappeared.
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PMID:[Diabetic foot. A clinical case]. 850 59

Skin microcirculation was investigated in 45 patients with long term diabetes and with severe, moderate or no neuropathy, and in 15 controls. Transcutaneous oxygen pressure (tcPO2) measurements on the forefoot were performed at 37 degrees C to assess local capillary flow at rest, during leg dependency and reactive hyperaemia, and also at 44 degrees C, including the response to oxygen inhalation. TcPO2 (37 degrees C) at rest was significantly elevated with an increasing degree of neuropathy (Controls: 4.8 +/- 3.7; patients without neuropathy: 4.2 +/- 2.9; with moderate neuropathy: 6.0 +/- 2.9 (p < 0.01); with severe neuropathy: 7.2 +/- 4.2 mmHg (p < 0.001)). Leg dependency resulted in a decrease of tcPO2 in the controls, while an increase was observed in 18.6% of the measurements in patients, reflecting a disturbed vasoconstrictor response. Regardless of neuropathy, absolute tcPO2 values during reactive hyperaemia were reduced in all patient groups as well as tcPO2 (44 degrees C) and its increase during oxygen breathing. Diabetic neuropathy is likely to increase local capillary flow, while the other differences to healthy controls may be contributed to a microcirculation disorder independent of neuropathy.
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PMID:Influence of diabetic neuropathy on skin microcirculation assessed by transcutaneous oxymetry. 853 44


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