Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prediabetes is associated with a length-dependent polyneuropathy that typically is sensory predominant and painful. A diagnosis of prediabetes should be sought in patients with otherwise idiopathic sensory-predominant neuropathy by doing a 2-hour oral glucose tolerance test. Fasting plasma glucose of 100 to 125 mg/dL or 2-hour glucose 140 to 199 mg/dL (impaired glucose tolerance) constitutes prediabetes. Most patients with neuropathy associated with prediabetes (NAP) are obese and show metabolic manifestations of insulin resistance, including hyperlipidemia and hypertension. Appropriate treatment addresses hyperglycemia, insulin resistance, and neuropathic pain. Professionally administered individualized diet and exercise counseling (modeled on the Diabetes Prevention Program) has been shown to be more effective than glucose-lowering medications in preventing progression from impaired glucose tolerance to diabetes, and is the mainstay of treatment for all patients with NAP. The goals of this therapy should be a 5% to 7% reduction in weight and an increase to 30 minutes of moderate exercise five times weekly. Patients with prediabetes are at increased risk for myocardial infarction, stroke, and peripheral vascular disease. Therefore, risk reduction with control of hypertension and hyperlipidemia is essential. Neuropathic pain troubles nearly every patient with NAP, and often limits aerobic exercise. No trials have specifically addressed the patient population with NAP, and neuropathic pain treatment closely follows recommendations for diabetic neuropathy. Gabapentin, lamotrigine, and tricyclic antidepressants are well-validated first-line therapies. Adjunctive therapy with opioids, nonsteroidal anti-inflammatory drugs often are necessary. Diet and exercise seem to reduce neuropathic pain in patients with NAP.
 ...
PMID:Polyneuropathy with Impaired Glucose Tolerance: Implications for Diagnosis and Therapy. 1561 Jul 5

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factor belonging to a nuclear hormone receptor superfamily, containing three isoforms (alpha, beta/delta, and gamma). PPARs play a critical physiological role as a primary lipid sensor and regulator of lipid metabolism. Thus, its ligands are clinically used for treatment of type 2 diabetes and hyperlipidemia. On the other hand, PPAR ligands exert the antineuroinflammatory activity through preventing upregulation of inflammatory mediators in animal models for neurodegenerative disease and autoimmune disease. Neuropathic pain and inflammatory pain, clinically important one, are chronically progressed and underlain by neuroinflammation. In a few years, some studies using experimental models emerge that administration of PPAR ligands reduces inflammatory pain and neuropathic pain. PPAR ligands repress expression of genes for inflammatory mediators involved in both pains, such as proinflammatory cytokines, by a molecular mechanism termed ligand-dependent direct transrepression. Alternative mechanism is independent of transcriptional regulation of target genes, such as inhibition of activity of ion channels involved in the development of inflammatory pain and neuropathic pain, and therefore the analgesic effect occurs with rapid onset. The effects of PPAR ligands on neuroinflammation in animal models suggest their possible use for treating human inflammatory pain and neuropathic pain.
 ...
PMID:PPAR and Pain. 1960 69

Approximately one in three people with diabetes is affected by diabetic distal symmetric sensorimotor polyneuropathy (DSPN), which represents a major health problem as it may present with excruciating neuropathic pain and is responsible for substantial morbidity, increased mortality and impaired quality of life. Neuropathic pain causes considerable interference with sleep, daily activities, and enjoyment of life. Treatment is based on four cornerstones: (1) intensive diabetes therapy and multifactorial risk intervention; (2) treatment based on pathogenetic mechanisms; (3) symptomatic treatment; and (4) avoidance of risk factors and complications. Recent experimental studies suggest a multifactorial pathogenesis of diabetic neuropathy. From the clinical point of view, it is important to note that, based on these pathogenetic mechanisms, therapeutic approaches could be derived, some of which are currently being evaluated in clinical trials. Management of chronic painful DSPN remains a challenge for the physician and should consider the following practical rules: the appropriate and effective drug has to be tried and identified in each patient by carefully titrating the dosage based on efficacy and side effects; lack of efficacy should be judged only after 2-4 weeks of treatment using an adequate dosage. Analgesic combination therapy may be useful, and potential drug interactions have to be considered given the frequent polypharmacy in people with diabetes. Not only increased alcohol consumption but also the traditional cardiovascular risk factors such as visceral obesity, hypertension, hyperlipidemia and smoking have a role in the development and progression of diabetic neuropathy and hence need to be prevented or treated.
 ...
PMID:Current concepts in the management of diabetic polyneuropathy. 2153 20