Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now increasingly being appreciated that a substantial proportion of subjects with prediabetes may exhibit peripheral neuropathy and/or neuropathic pain. The reverse is also true, inasmuch as examining patients with idiopathic peripheral neuropathy will frequently reveal prediabetes. In the general population, the prevalence of neuropathy in prediabetes is intermediate between overt diabetes and subjects with normoglycemia. This prediabetic neuropathy is, generally, milder in comparison to diabetic neuropathy and mainly affects small fibers mediating sensory function. Hyperglycemia, microangiopathy, dyslipidemia and the metabolic syndrome have been implicated as pathogenic mechanisms. In practice, therapy of prediabetic neuropathy should be addressed towards normoglycemia and correction of cardiovascular risk factors. However, additional work is needed to establish the long-term results of this approach.
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PMID:Prediabetic neuropathy: does it exist? 2256 52

Dyslipidemia has been identified as an important pathogenic risk factor for diabetic neuropathy, but current animal models do not adequately reproduce the lipid profile observed in human diabetics (increased triglycerides with an elevated LDL-cholesterol and reduced HDL-cholesterol). High fat feeding of mice produces hyperlipidemia, but mice are resistant to increases in the LDL to HDL ratio, reducing the potential for peripheral lipid deposits to impact neuropathy, as is postulated to occur in human subjects. Genetic manipulations provide an alternative approach to reproducing a neuropathic plasma lipid profile. Based on findings from the atherosclerosis literature, we began with knockout of ApoE. Since knockout of ApoE alone only partially mimics the human diabetic lipid profile, we examined the impact of its combination with a well-characterized model of type 2 diabetes exhibiting neuropathy, the db/db mouse. We added further gene manipulations to increase hyperlipidemia by using mice with both ApoE and ApoB48 knockout on the ob/+ (leptin mutation) mice. In all of these models, we found that either the db/db or ob/ob genotypes had increased body weight, hyperlipidemia, hyperglycemia, and evidence of neuropathy compared with the control groups (db/+ or ob/+, respectively). We found that ApoE knockout combined with leptin receptor knockout produced a lipid profile most closely modeling human dyslipidemia that promotes neuropathy. ApoE knockout combined with additional ApoB48 and leptin knockout produced similar changes of smaller magnitude, but, notably, an increase in HDL-cholesterol. Our data suggest that the overall effects of ApoE knockout, either directly upon nerve structure and function or indirectly on lipid metabolism, are insufficient to significantly alter the course of diabetic neuropathy. Although these models ultimately do not deliver optimal lipid profiles for translational diabetic neuropathy research, they do present glycemic and lipid profile properties of value for future therapeutic investigations.
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PMID:Apolipoprotein E knockout as the basis for mouse models of dyslipidemia-induced neuropathy. 2393 75

Diabetes is associated with a variety of chronic and acute neuropathies. In this article, the authors summarize the clinical features of the most common diabetic neuropathies, focusing on those for which therapy is available or under active investigation. Distal symmetric polyneuropathy (DSP) is the most common form. Potential treatments for DSP are discussed in four broad themes: (1) medication and lifestyle therapy to improve hyperglycemia, insulin resistance, and attendant features of metabolic syndrome, including obesity and dyslipidemia; (2) pharmacologic therapy to alter neuropathy natural history aimed at rational targets from known pathophysiology; (3) symptomatic relief of neuropathic pain; and (4) treatment to prevent complications of neuropathy, including stasis ulcers and falls. The approach to the most common acute diabetic neuropathies is also reviewed.
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PMID:The diabetic neuropathies: practical and rational therapy. 2311 44

There is accumulating evidence for the mutual relationship between peripheral neuropathy and impaired glucose tolerance (IGT). The key factor in the pathogenesis of neuropathy in IGT is postprandial hyperglycemia, which induces increased oxidative stress, endothelial dysfunction, and activation of both protein kinase C and the polyol pathway, leading to impaired neuronal metabolism and DNA damage. Other pathogenic factors include dyslipidemia and the metabolic syndrome. The cornerstone of management is improved glycemic control, although a long sustainable effect has not been documented yet, calling for further supportive trials. Secondary therapeutic targets encompass hypolipidemic and antihypertensive treatment, smoking cessation and weight loss. The increasing awareness of peripheral neuropathy in IGT is expected to improve healthcare provision in subjects with this condition.
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PMID:Polyneuropathy in impaired glucose tolerance: is postprandial hyperglycemia the main culprit? A mini-review. 2320 96

The incidence of diabetes is escalating worldwide and, consequently, this has become a major health care problem. Moreover, both type 1 and type 2 diabetes are associated with significantly accelerated rates of microvascular complications, including retinopathy, nephropathy, and neuropathy, as well as macrovascular complications such as atherosclerotic cardiovascular and hypertensive diseases. Key factors have been implicated in leading to these complications, including hyperglycemia, insulin resistance, dyslipidemia, advanced glycation end products, growth factors, inflammatory cytokines/chemokines, and related increases in cellular oxidant stress (including mitochondrial) and endoplasmic reticulum stress. However, the molecular mechanisms underlying the high incidence of diabetic complications, which often progress despite glycemic control, are still not fully understood. MicroRNAs (miRNAs) are short noncoding RNAs that have elicited immense interest in recent years. They repress target gene expression via posttranscriptional mechanisms and have diverse cellular and biological functions. Herein, we discuss the role of miRNAs in the pathobiology of various diabetic complications, their involvement in oxidant stress, and also the potential use of differentially expressed miRNAs as novel diagnostic biomarkers and therapeutic targets.
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PMID:MicroRNAs: potential mediators and biomarkers of diabetic complications. 2377 Jan 98

Emerging clinical evidence now suggests that dyslipidemia may be strongly linked with the development and progression of neuropathy in diabetic patients, and dyslipidemia is considered an important risk factor for the development of diabetic neuropathy. However, because of important species differences, current animal models fall short of accurately replicating human diabetic dyslipidemia. Rodents resist expansion in low-density lipoprotein cholesterol (LDL-C) and typically maintain or increase high-density lipoprotein cholesterol (HDL-C), despite prolonged high-fat feeding. Here, we discuss the findings of Hinder et al., in which they utilized novel genetic experimental approaches to develop a diabetic mouse model with human-like dyslipidemia. The authors created a mouse with an apolipoprotein E (ApoE) knockout in conjunction with a leptin receptor mutation. A triple mutant mouse with both ApoE and apolipoprotein B48 knockout and leptin deficiency was also created in an effort to generate a model of diabetic dyslipidemia that better mimics the human condition. The long-term goal of these studies is to develop more faithful models to address how hyperglycemia and hyperlipidemia may drive the development and progression of neuropathy. Hinder and colleagues were successful at creating a diabetic mouse model with severe hypertriglyceridemia, hypercholesterolemia, and a significant increase in the total cholesterol to HDL-C ratio. This work was successful in establishing a model of diabetic dyslipidemia that more closely emulates the poor lipid profile observed in human diabetic patients with neuropathy. This commentary will also review current models used to study the effects of dyslipidemia on diabetic neuropathy and highlight a proposed mechanism for the role of dyslipidemia in the pathogenesis of diabetic neuropathy.
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PMID:Chewing the fat: genetic approaches to model dyslipidemia-induced diabetic neuropathy in mice. 2305 59

In recent years, there is growing evidence that plant-foods polyphenols, due to their biological properties, may be unique nutraceuticals and supplementary treatments for various aspects of type 2 diabetes mellitus. In this article we have reviewed the potential efficacies of polyphenols, including phenolic acids, flavonoids, stilbenes, lignans and polymeric lignans, on metabolic disorders and complications induced by diabetes. Based on several in vitro, animal models and some human studies, dietary plant polyphenols and polyphenol-rich products modulate carbohydrate and lipid metabolism, attenuate hyperglycemia, dyslipidemia and insulin resistance, improve adipose tissue metabolism, and alleviate oxidative stress and stress-sensitive signaling pathways and inflammatory processes. Polyphenolic compounds can also prevent the development of long-term diabetes complications including cardiovascular disease, neuropathy, nephropathy and retinopathy. Further investigations as human clinical studies are needed to obtain the optimum dose and duration of supplementation with polyphenolic compounds in diabetic patients.
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PMID:Dietary polyphenols as potential nutraceuticals in management of diabetes: a review. 2393 49

Diabetes is a complex endocrine/metabolic disease with many related complications including micro-vascular and macrovascular problems such as cardiomyopathy, nephropathy, neuropathy and retinopathy. Generally, type-1 diabetes is caused by autoimmune- mediated destruction of pancreatic beta cells leading to insulin deficiency. This is usually accompanied by dyslipidemia, enhanced hyperglycemia-mediated oxidative stress, endothelial-cell dysfunction and apoptosis. For decades, type-1 diabetes has been traditionally known as insulin-dependent, while type-2 as non-insulin dependent diabetes. However, it is becoming increasingly clear that insulin deficiency and insulin resistance are manifested in both forms of diabetes at different stages. Thus, it may be time revisit the nomenclature and adjust it to reflect these observations of insulin deficiency and insulin resistance in both forms of diabetes to avoid ambiguity when discussing forms of diabetes. Emerging evidence indicates that the heme-oxygenase (HO) system and related products including carbon monoxide, ferritin and biliverdin are capable of suppressing immune/inflammatory response, and abate oxidative stress and apoptosis. More importantly, upregulating the HO-system increases pancreatic beta-cell insulin release and reduce hyperglycemia in different diabetic models. Similarly, carbon monoxide, a product of the HO-catalyzed degradation of heme also enhances insulin production and improves glucose metabolism. Since excessive immune/inflammatory responses coupled to elevated apoptosis are among the cardinal pathophysiological features of type-1 diabetes, this review highlights the role of the HO-system and related products such as carbon monoxide and bilirubin in the modulation of apoptosis and immune response, and the beneficial effects of the HO-system in the pathogenesis of type-1 diabetes and related cardiometabolic complications.
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PMID:The heme oxygenase system and type-1 diabetes. 2397 2

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is associated with both microvascular (neuropathy, nephropathy and retinopathy) and macrovascular complications [coronary artery disease (CAD), stroke, carotid artery disease and peripheral artery disease (PAD)]. Apart from acting on diabetic dyslipidemia, statins were shown to exert beneficial effects on several diabetic complications as well as other cardiovascular (CVD) risk predictors such as endothelial dysfunction, inflammation, oxidative stress, chronic kidney disease (CKD), non-alcoholic fatty liver disease (NAFLD), metabolic syndrome (MetS), obstructive sleep apnea syndrome (OSAS) and hyperuricemia. Several clinical trials involving T2DM patients have reported significant reductions in coronary and cerebrovascular events following statin treatment. However, a modest statin-related risk of new-onset diabetes (NOD) has been reported but that did not [corrected] outweigh the benefit of CVD risk reduction in high-risk individuals. Overall, statin use is beneficial and should be recommended in diabetic patients to target their increased CVD risk.
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PMID:The role of statins in the treatment of type 2 diabetes mellitus: an update. 2404 Aug 75

One of the tissues or organs affected by diabetes is the nervous system, predominantly the peripheral system (peripheral polyneuropathy and/or painful peripheral neuropathy) but also the central system with impaired learning, memory and mental flexibility. The aim of this study was to test the hypothesis that the pre-diabetic or diabetic condition caused by a high-fat diet (HFD) can damage both the peripheral and central nervous systems. Groups of C57BL6 and Swiss Webster mice were fed a diet containing 60% fat for 8 months and compared to control and streptozotocin (STZ)-induced diabetic groups that were fed a standard diet containing 10% fat. Aspects of peripheral nerve function (conduction velocity, thermal sensitivity) and central nervous system function (learning ability, memory) were measured at assorted times during the study. Both strains of mice on HFD developed impaired glucose tolerance, indicative of insulin resistance, but only the C57BL6 mice showed statistically significant hyperglycemia. STZ-diabetic C57BL6 mice developed learning deficits in the Barnes maze after 8 weeks of diabetes, whereas neither C57BL6 nor Swiss Webster mice fed a HFD showed signs of defects at that time point. By 6 months on HFD, Swiss Webster mice developed learning and memory deficits in the Barnes maze test, whereas their peripheral nervous system remained normal. In contrast, C57BL6 mice fed the HFD developed peripheral nerve dysfunction, as indicated by nerve conduction slowing and thermal hyperalgesia, but showed normal learning and memory functions. Our data indicate that STZ-induced diabetes or a HFD can damage both peripheral and central nervous systems, but learning deficits develop more rapidly in insulin-deficient than in insulin-resistant conditions and only in Swiss Webster mice. In addition to insulin impairment, dyslipidemia or adiponectinemia might determine the neuropathy phenotype.
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PMID:Role of insulin signaling impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice. 2476 91


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