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)

L-Carnitine (LC) and acetyl-L-carnitine (ALC) play major roles in cell energy and lipid metabolism. Supplementation with these nutrients, which are highly popular in USA, has been associated with favorable effects, including anti-oxidant action, neuro- and cardioprotection, immunomodulation, and cognitive enhancement. Patients with HIV infection and undergoing highly active antiretroviral therapy (HAART) often develop complications, such as polyneuropathy, skeletal myopathy, dyslipidemia and lipodystrophy, which have been linked to mitochondrial dysfunction. Moreover, these patients are often LC-deficient. Thus, they may benefit from LC and ALC supplementation. Indeed, oral, i.v., or i.m. administration of large doses of LC and/or ALC to HIV positive subjects untreated/treated with HAART was shown to: (1) increase the number of CD4 cells and reduce lymphocyte apoptosis; (2) improve symptoms of polyneuropathy; (3) prevent cardiovascular damage from wasting and diarrhea syndromes; (4) decrease serum levels of triglycerides and TNFalpha. No significant toxicities were associated with LC and ALC treatment. Although promising, most of these findings derive from small uncontrolled clinical trials. Further research is warranted to prove the efficacy and safety of LC and ALC supplementation in patients with complications of HIV infection and HAART.
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PMID:L-Carnitine and acetyl-L-carnitine in the treatment of complications associated with HIV infection and antiretroviral therapy. 1612 Mar 81

Metabolic syndrome (MS) encompasses a series of diseases which, when combined, increase vascular risk more than the sum of their individual risks. Insulin resistance (IR) is one of the basic components of MS. - Abdominal fat distribution is an IR marker and is associated to factors increasing vascular risk such as dyslipidemia, high blood pressure, and hyperglycemia, components of the so-called metabolic syndrome. - IR is related to glomerular sclerosis and renal failure through several mechanisms, Including genetic and environmental factors, and stimulation of the renin-angiotensin-aldosterone system. - IR usually precedes development of DM, and therefore contributes to its early identification. MS increases the risk of chronic complications from DM and is associated to an increased prevalence of cardiovascular disease, particularly coronary heart disease, increasing mortality from this cause. - The presence of MS in DM2 is usually associated to a greater prevalence of microalbuminuria or proteinuria and peripheral polyneuropathy.
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PMID:[Metabolic syndrome and kidney disease]. 1901 36

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

To establish the role of the metabolic state in the pathogenesis of polyneuropathy, an age- and sex-matched, longitudinal study in rats fed high-fat and high-sucrose diets (HFSD) or high-fat, high-sucrose and high-salt diets (HFSSD) relative to controls was performed. Time courses of body weight, systolic blood pressure, fasting plasma glucose (FPG), insulin, free fatty acids (FFA), homeostasis model assessment-insulin resistance index (HOMA-IR), thermal and mechanical sensitivity and motor coordination were measured in parallel. Finally, large and small myelinated fibers (LMF, SMF) as well as unmyelinated fibers (UMF) in the sciatic nerves and ascending fibers in the spinal dorsal column were quantitatively assessed under electron microscopy. The results showed that early metabolic syndrome (hyperinsulinemia, dyslipidemia, and hypertension) and prediabetic conditions (impaired fasting glucose) could be induced by high energy diet, and these animals later developed painful polyneuropathy characterized by myelin breakdown and LMF loss in both peripheral and central nervous system. In contrast SMF and UMF in the sciatic nerves were changed little, in the same animals. Therefore the phenomenon that high energy diets induce bilateral mechanical, but not thermal, pain hypersensitivity is reflected by severe damage to LMF, but mild damage to SMF and UMF. Moreover, dietary sodium (high-salt) deteriorates the neuropathic pathological process induced by high energy diets, but paradoxically high salt consumption, may reduce, at least temporarily, chronic pain perception in these animals.
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PMID:High energy diets-induced metabolic and prediabetic painful polyneuropathy in rats. 2345 Dec 27

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

Diabetic neuropathies (DNs) differ in clinical course, distribution, fiber involvement (type and size), and pathophysiology, the most typical type being a length-dependent distal symmetric polyneuropathy (DSP) with differing degrees of autonomic involvement. The pathogenesis of diabetic DSP is multifactorial, including increased mitochondrial production of free radicals due to hyperglycemia-induced oxidative stress. Mechanisms that impact neuronal activity, mitochondrial function, membrane permeability, and endothelial function include formation of advanced glycosylation end products, activation of polyol aldose reductase signaling, activation of poly(ADP ribose) polymerase, and altered function of the Na(+)/K(+)-ATPase pump. Hyperglycemia-induced endoplasmic reticulum stress triggers several neuronal apoptotic processes. Additional mechanisms include impaired nerve perfusion, dyslipidemia, altered redox status, low-grade inflammation, and perturbation of calcium balance. Successful therapies require an integrated approach targeting these mechanisms. Intensive glycemic control is essential but is insufficient to prevent onset or progression of DSP, and disease-modifying treatments for DSP have been disappointing. Atypical forms of DN include subacute-onset sensory (symmetric) or motor (asymmetric) predominant conditions that are frequently painful but generally self-limited. DNs are a major cause of disability, associated with reduced quality of life and increased mortality.
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PMID:Diabetic neuropathy: mechanisms, emerging treatments, and subtypes. 2495 24

The metabolic effect of bariatric surgery is well-established and is considered to be self-evident in morbidly obese patients with a body mass index (BMI) > 40 kg/m(2). Metabolic surgery performed on patients with obesity grades II (BMI 35-40 kg/m(2)) and I (BMI 30-35 kg/m(2)) according to the World Health Organization (WHO) has increased in recent years; however, the indications for metabolic surgery in obesity grades I and II are currently under debate due to insufficient evidence. In the last 5 years several highly qualified randomized clinical trials have been published which evaluated the effect of metabolic surgery in patients with obesity grades I and II in comparison to conservative therapy. Based on these data the efficacy of metabolic surgery in short-term follow-up (12-36 months) is unquestionable when compared to conservative therapy according to the current guidelines. Besides improved glycemic control and remission of diabetes, metabolic surgery has the potential to have a positive influence on diabetic complications, such as diabetic retinopathy, nephropathy and polyneuropathy, as well as on comorbidities, such as arterial hypertension and dyslipidemia. Future clinical trials should address the long-term (> 36 months) effects of metabolic surgery, patient selection criteria and choice of procedure.
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PMID:[Clinical evidence for metabolic surgery]. 2531 39

Diabetic distal symmetric sensorimotor polyneuropathy (DSPN) represents a major health problem, associated with excruciating neuropathic pain, increased morbidity and impaired quality of life. The understanding of its epidemiology is difficult due to methodological issues. Inconsistency in the selection of diagnostic procedures renders comparison between studies problematic. Further problems arise from selection bias due to the inclusion of hospital-based populations. DSPN affects approximately 30% of hospital-based populations, 20% of community-based samples, and 10% of the diabetic population identified by screening. Chronic painful DSPN is present in 13-26% of diabetic patients. Between 25% and 62% of patients with idiopathic peripheral neuropathy have prediabetes. Among pre-diabetic subjects, 11-25% exhibit peripheral neuropathy and 13-26% neuropathic pain. Evidence from population-based studies indicates that there is a gradient in the prevalence of neuropathy. Indeed, the highest frequency is found in patients with manifest diabetes mellitus, followed by individuals with impaired glucose tolerance, then impaired fasting glucose and, finally, those with normoglycemia. The most important etiologic factors are poor glycemic control, age, diabetes duration, visceral obesity, height, hypertension, age, smoking, hypoinsulinemia, and dyslipidemia. Clinic-based data suggest that DSPN is associated with increased mortality in diabetes, but confirmatory prospective population-based studies are required.
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PMID:Epidemiology of polyneuropathy in diabetes and prediabetes. 2541 Feb 10

Distal symmetric sensorimotor polyneuropathy (DSPN) is the most common neurological manifestation in diabetes. Major risk factors of DSPN include diabetes duration, hyperglycemia, and age, followed by prediabetes, hypertension, dyslipidemia, and obesity. Height, smoking, insulin resistance, hypoinsulinemia, and others represent an additional risk. Importantly, hyperglycemia, hypertension, dyslipidemia, obesity, and smoking are modifiable. Stringent glycemic control has been shown to be effective in type 1, but not to the same extent in type 2 diabetes. Antilipidemic treatment, especially with fenofibrate, and multi-factorial intervention have produced encouraging results, but more experience is necessary. The major comorbidities of DSPN are depression, autonomic neuropathy, peripheral arterial disease, cardiovascular disease, nephropathy, retinopathy, and medial arterial calcification. Knowledge of risk factors and comorbidities has the potential to enrich the therapeutic strategy in clinical practice as part of the overall medical care for patients with neuropathy. This article provides an updated overview of DSPN risk factors and comorbidities.
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PMID:Risk Factors and Comorbidities in Diabetic Neuropathy: An Update 2015. 2667 61

The purpose of current study aims to investigate the development and progression of diabetic retinopathy (DR) in patients with diabetic nephropathy (DN) in a nationwide population-based cohort in Taiwan. Newly diagnosed DN patients and age- and sex-matched controls were identified from the Taiwanese Longitudinal Health Insurance Database from 2000 to 2010. We studied the effects of age, sex, hypertension, dyslipidemia, diabetic polyneuropathy (DPN), and medications on the development of nonproliferative DR (NPDR), proliferative DR (PDR), and diabetic macular edema (DME) in patients with DN. Cox proportional hazard regression analyses were used to estimate the adjusted hazard ratios (HRs) of the development of DR. Our results show that the adjusted HRs of NPDR and PDR were 5.01 (95% confidence interval (CI) = 4.68-5.37) and 9.7 (95% CI = 8.15-11.5), respectively, in patients with DN as compared with patients in the non-DN cohort. At 5-year follow-up, patients with DN showed an increased HR of NPDR progression to PDR (HR = 2.26, 95% CI = 1.68-3.03), and the major comorbidities were hypertension (HR = 1.23, 95% CI = 1.10-1.38 with NPDR; HR = 1.33, 95% CI = 1.02-1.72 with PDR) and DPN (HR = 2.03, 95% CI = 1.72-2.41 in NPDR; HR = 2.95, 95% CI = 2.16-4.03 in PDR). Dyslipidemia increased the HR of developing NPDR but not PDR or DME. Moreover, DN did not significantly affect DME development (HR = 1.47, 95% CI = 0.87-2.48) or progression (HR = 0.37, 95% CI = 0.11-1.20). We concluded that DN was an independent risk factor for DR development and progression; however, DN did not markedly affect DME development in this study, and the potential association between these disorders requires further investigation.
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PMID:Diabetic Retinopathy in Patients with Diabetic Nephropathy: Development and Progression. 2756 83


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