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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is difficult to establish predictors for diabetic neuropathy because no generally accepted criteria of its diagnosis exist. In previous investigations risk factors profiles for neuropathy differ markedly. The aim of this study was to assess risk predictors for diabetic neuropathy in relation to different criteria of its diagnosis. Ninety-five diabetic patients entered the study. The exclusion criteria included uremia, alcohol abuse and radiculopathy. Control group consisted of 43 healthy volunteers. All patients underwent the clinical assessment, instrumental evaluation of superficial and deep sensation, tests of cardiovascular autonomic function and nerve conduction studies. According to the performed assessment patients were classified into following groups: without neuropathy, suspicion of neuropathy, neuropathy confirmed in clinical examination, neuropathy confirmed in electrophysiological testing, autonomic neuropathy. Analysis showed that the most important predictors in patients with subjective symptoms were type 2 diabetes mellitus, diabetes duration and age of patients. When neuropathy was diagnosed according to the clinical examination, predictors included type 2 diabetesmellitus and duration of the disease. In the cases of neuropathy confirmed by electrophysiological studies and autonomic neuropathy, only diabetes duration appeared to be a significant predictor. Our study demonstrated that predictors for diabetic neuropathy varied in relation to different diagnostic criteria and where the most important predictor for all forms of neuropathy is duration of diabetes. This result indicates the need for frequent screening tests in patients with long duration of the disease, irrespective of its metabolic control, patients' age or type of diabetes.
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PMID:[Predictors for diabetic neuropathy according to applied criteria of its diagnosis]. 1271 13

Diabetes is a major cause of mortality and morbidity due to the long term microvascular complications of this disease. There is now convincing evidence to show that genetic factors together with elevated blood glucose play an important role in the susceptibility to diabetic nephropathy as well as retinopathy. The polyol pathway is thought to play an important role in the pathogenesis of diabetic microvascular complications. Aldose reductase is the first and rate-limiting enzyme of the polyol pathway. Polymorphisms in the promoter region as well as elsewhere in the gene have been associated with susceptibility to nephropathy, retinopathy as well as diabetic neuropathy. These associations have been replicated in patients with either type 1 or type 2 diabetes mellitus as well as across ethnic groups. These polymorphisms in the promoter region are also associated with expression of the gene. Although clinical trials using inhibitors of aldose reductase to treat diabetic microvascular complications have largely been unsuccessful, the identification of the susceptibility genes may help in the design of future drug regimens.
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PMID:Polymorphisms of the aldose reductase gene and susceptibility to diabetic microvascular complications. 1287 Nov 36

We investigated the chronic effect of a new antidiabetic agent, trans-4-(methylcyclohexyl)-4-oxobutyric acid (JTT-608), in Goto-Kakizaki rats, a genetic model of non-obese type II diabetes mellitus. The rats were fed a liquid meal, three times a day, for 12 weeks. The rats were treated orally with JTT-608 (10-100 mg/kg) 10 min before each meal. Fasting blood glucose, triglyceride and hemoglobin A1c levels were reduced by JTT-608 at all dose levels during the experimental period. Blood glucagon-like peptide-1 level with 100 mg/kg JTT-608 increased at the end of the treatment period. JTT-608 (30-100 mg/kg) reduced urinary protein levels after administration for 5-12 weeks. In Goto-Kakizaki rats showing slight diabetic renal lesions, pathological examination revealed that JTT-608 reduced the incidence of vacuolation in renal tubules. JTT-608 (30-100 mg/kg) ameliorated the reduced motor nerve conduction velocities observed in the Goto-Kakizaki rats after administration for 12 weeks. We conclude that chronic administration of JTT-608 produces good blood glucose control and gradually arrests the development of diabetic neuropathy and nephropathy.
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PMID:Antidiabetic effect of chronic administration of JTT-608, a new hypoglycemic agent, in diabetic Goto-Kakizaki rats. 1296 61

During treatment for type 2 diabetes with a diabetic diet (without medication), a 61-year-old Japanese man suddenly developed hyposmia. The fasting plasma glucose was 208 mg/dl and haemoglobin A1c was 8.6%. On investigation, there were no indications of disease of the brain, or the nasal or paranasal sinuses. The intravenous olfaction test yielded no response, indicating suspected neural hyposmia. After 6 months, the symptoms of hyposmia improved without medication, and the intravenous olfaction test results were normal. This clinical course is very similar to that seen with diabetic neuropathy of the third and sixth cranial nerves. We speculate that hyposmia in this case may have been caused by diabetic mononeuropathy of the first cranial nerve.
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PMID:Acute hyposmia in type 2 diabetes. 1458 16

Diabetic polyneuropathy is the most common complication of diabetes mellitus. Several interactive pathogenetic mechanisms have been identified mainly in streptozotocin-induced diabetes in rats and have been ascribed to hyperglycemia. Over the last number of years it is becoming increasingly clear that diabetic neuropathy differs in type 1 and type 2 diabetes in humans and in murine models that more accurately mimic the human disorders. Beside hyperglycemia, attention is increasingly being paid to the pathogenetic roles of insulin and C-peptide deficiencies, particularly in type 1 diabetic neuropathy. There is now evidence to suggest that insulin and C-peptide deficiencies are mainly responsible for perturbations of neurotrophic factors and contribute to oxidative stress in diabetic nerve. This may also be true for apoptotic phenomena afflicting both the peripheral and central nervous systems in diabetes. The new data have lead to re-evaluations of pathogenetic components in this complex disorder, and their further exploration is likely to form a more refined basis for future therapeutic and preventive measures.
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PMID:New insights into the metabolic and molecular basis for diabetic neuropathy. 1462 88

Diabetic neuropathy develops as a result of hyperglycemia-induced local metabolic and microvascular changes in both type I and type II diabetes mellitus. Diabetic neuropathy shows slower impulse conduction, axonal degeneration, and impaired regeneration. Diabetic neuropathy affects peripheral, central, and visceral sensorimotor and motor nerves, causing improper locomotor and visceral organ dysfunctions. The pathogenesis of diabetic neuropathy is complex and involves multiple pathways. Lack of success in preventing neuropathy, even with successful treatment of hyperglycemia, suggests the presence of early mediators between hyperglycemia-induced metabolic and enzymatic changes and functional and structural properties of Schwann cells (SCs) and axons. It is feasible that once activated, such mediators can act independently of the initial metabolic stimulus to modulate SC-axonal communication. Neuropoietic cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), tumor necrosis factor alpha (TNF-alpha), and transforming growth factor beta (TGF-beta), exhibit pleiotrophic effects on homeostasis of glia and neurons in central, peripheral, and autonomic nervous system. These cytokines are produced locally by resident and infiltrating macrophages, lymphocytes, mast cells, SCs, fibroblasts, and sensory neurons. Metabolic changes induced by hyperglycemia lead to dysregulation of cytokine control. Moreover, their regulatory roles in nerve degeneration and regeneration may potentially be utilized for the prevention and/or therapy of diabetic neuropathy.
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PMID:Role of neuropoietic cytokines in development and progression of diabetic polyneuropathy: from glucose metabolism to neurodegeneration. 1466 51

Neuropathy is one of the most debilitating complications of both type 1 and type 2 diabetes, with estimates of prevalence between 50-90% depending on the means of detection. Diabetic neuropathies are heterogeneous and there is variable involvement of large myelinated fibers and small, thinly myelinated fibers. Many of the neuronal abnormalities in diabetes can be duplicated by experimental depletion of specific neurotrophic factors, their receptors or their binding proteins. In experimental models of diabetes there is a reduction in the availability of these growth factors, which may be a consequence of metabolic abnormalities, or may be independent of glycemic control. These neurotrophic factors are required for the maintenance of the neurons, the ability to resist apoptosis and regenerative capacity. The best studied of the neurotrophic factors is nerve growth factor (NGF) and the related members of the neurotrophin family of peptides. There is increasing evidence that there is a deficiency of NGF in diabetes, as well as the dependent neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) that may also contribute to the clinical symptoms resulting from small fiber dysfunction. Similarly, NT3 appears to be important for large fiber and IGFs for autonomic neuropathy. Whether the observed growth factor deficiencies are due to decreased synthesis, or functional, e.g. an inability to bind to their receptor, and/or abnormalities in nerve transport and processing, remains to be established. Although early studies in humans on the role of neurotrophic factors as a therapy for diabetic neuropathy have been unsuccessful, newer agents and the possibilities uncovered by further studies should fuel clinical trials for several generations. It seems reasonable to anticipate that neurotrophic factor therapy, specifically targeted at different nerve fiber populations, might enter the therapeutic armamentarium.
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PMID:Nerve growth factor and diabetic neuropathy. 1466 49

Sensory neuropathy is a prominent component of diabetic neuropathy. It is not entirely clear how diabetes influences skin innervation, and whether these changes are correlated with clinical signs and laboratory findings. To investigate these issues, we performed skin biopsies on the distal leg of 38 consecutive type 2 diabetic patients with sensory symptoms in lower limbs (25 males and 13 females, aged 56.2 +/- 9.4 years) and analysed the correlations of intraepidermal nerve fibre (IENF) densities in skin with glycaemic status (duration of diabetes, HbA1C, and fasting and post-prandial glucose levels), and functional parameters of small fibres (warm and cold thresholds) and large fibres (vibratory threshold and parameters of nerve conduction studies). Clinically, 23 patients (60.5%) had signs of small-fibre impairment, and 19 patients (50.0%) had signs of large-fibre impairment. IENF densities were much lower in diabetic patients than in age- and gender-matched controls (1.794 +/- 2.120 versus 9.359 +/- 3.466 fibres/mm, P < 0.0001), and 81.6% (31/38) of diabetic patients had reduced IENF densities. IENF densities were negatively associated with the duration of diabetes (standardized coefficient: -0.422, P = 0.015) by analysis with a multivariate linear regression model. Abnormal results of functional examinations were present in 81.6% (warm threshold), 57.9% (cold threshold), 63.2% (vibratory threshold) and 49% (amplitude of sural sensory action potential) of diabetic patients. Among the three sensory thresholds, the warm threshold temperature had the highest correlation with IENF densities (standardized coefficient: -0.773, P < 0.0001). On nerve conduction studies in lower-limb nerves, there were abnormal responses in 54.1% of sural nerves, and 50.0% of peroneal nerves. Of neurophysiological parameters, the amplitude of the sural sensory action potential had the highest correlation with IENF density (standardized coefficient: 0.739, P < 0.0001). On clinical examination, 15 patients showed no sign of small-fibre impairment, but seven of these patients had reduced IENF densities. In conclusion, small-fibre sensory neuropathy presenting with reduced IENF densities and correlated elevation of warm thresholds is a major manifestation of type 2 diabetes. In addition, the extent of skin denervation increases with diabetic duration.
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PMID:Skin denervation in type 2 diabetes: correlations with diabetic duration and functional impairments. 1556 91

Na+,K(+)-ATPase is an ubiquitous membrane enzyme that allows the extrusion of three sodium ions from the cell and two potassium ions from the extracellular fluid. Its activity is decreased in many tissues of streptozotocin-induced diabetic animals. This impairment could be at least partly responsible for the development of diabetic complications. Na+,K(+)-ATPase activity is decreased in the red blood cell membranes of type 1 diabetic individuals, irrespective of the degree of diabetic control. It is less impaired or even normal in those of type 2 diabetic patients. The authors have shown that in the red blood cells of type 2 diabetic patients, Na+,K(+)-ATPase activity was strongly related to blood C-peptide levels in non-insulin-treated patients (in whom C-peptide concentration reflects that of insulin) as well as in insulin-treated patients. Furthermore, a gene-environment relationship has been observed. The alpha-1 isoform of the enzyme predominant in red blood cells and nerve tissue is encoded by the ATP1A1 gene. A polymorphism in the intron 1 of this gene is associated with lower enzyme activity in patients with C-peptide deficiency either with type 1 or type 2 diabetes, but not in normal individuals. There are several lines of evidence for a low C-peptide level being responsible for low Na+,K(+)-ATPase activity in the red blood cells. Short-term C-peptide infusion to type 1 diabetic patients restores normal Na+,K(+)-ATPase activity. Islet transplantation, which restores endogenous C-peptide secretion, enhances Na+,K(+)-ATPase activity proportionally to the rise in C-peptide. This C-peptide effect is not indirect. In fact, incubation of diabetic red blood cells with C-peptide at physiological concentration leads to an increase of Na+,K(+)-ATPase activity. In isolated proximal tubules of rats or in the medullary thick ascending limb of the kidney, C-peptide stimulates in a dose-dependent manner Na+,K(+)-ATPase activity. This impairment in Na+,K(+)-ATPase activity, mainly secondary to the lack of C-peptide, plays probably a role in the development of diabetic complications. Arguments have been developed showing that the diabetes-induced decrease in Na+,K(+)-ATPase activity compromises microvascular blood flow by two mechanisms: by affecting microvascular regulation and by decreasing red blood cell deformability, which leads to an increase in blood viscosity. C-peptide infusion restores red blood cell deformability and microvascular blood flow concomitantly with Na+,K(+)-ATPase activity. The defect in ATPase is strongly related to diabetic neuropathy. Patients with neuropathy have lower ATPase activity than those without. The diabetes-induced impairment in Na+,K(+)-ATPase activity is identical in red blood cells and neural tissue. Red blood cell ATPase activity is related to nerve conduction velocity in the peroneal and the tibial nerve of diabetic patients. C-peptide infusion to diabetic rats increases endoneural ATPase activity in rat. Because the defect in Na+,K(+)-ATPase activity is also probably involved in the development of diabetic nephropathy and cardiomyopathy, physiological C-peptide infusion could be beneficial for the prevention of diabetic complications.
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PMID:C-peptide, Na+,K(+)-ATPase, and diabetes. 1519 70

Diabetic amyotrophy is a distinctive form of diabetic neuropathy usually characterized by the abrupt onset of pain and asymmetric proximal leg weakness and wasting. Involvement of the upper limbs is unusual, and prognosis is said to be good. We describe two patients, each with type II diabetes mellitus, who presented with diabetic amyotrophy progressing to severe quadriparesis. One patient remains severely disabled. The clinical spectrum of diabetic amyotrophy includes progression to severe quadriparesis.
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PMID:Diabetic amyotrophy progressing to severe quadriparesis. 1537 38


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