| Thiazolidinediones and their fluid-related adverse effects: facts, fiction and putative management strategies. | |
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MedLine Citation:
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PMID: 17722967 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thiazolidinediones (TZDs) or glitazones are agents that are widely used for the treatment of type 2 diabetes mellitus. These drugs have a multitude of therapeutic effects including reduction in insulin resistance and hyperglycaemia, anti-inflammatory effects and amelioration of hypertension, microalbuminuria and hepatic steatosis. The TZD molecular target, peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear transcription factor, is expressed diffusely in humans, including many tissues comprising the cardiovascular and renal systems. This suggests a potential for TZDs to elicit perturbing effects on these systems, which are independent of their effects on glucose and lipid metabolism. One of the most common adverse effects of TZDs is fluid retention, which can result in, or exacerbate, oedema and congestive heart failure (CHF). The frequency of peripheral oedema is approximately 5% when TZDs are used in mono- or combination oral therapy, and about 15% when used with insulin. Patients with type 2 diabetes are at high risk of myriad morbid complications, including CHF. The development of CHF, particularly in the elderly, is a harbinger of premature mortality. TZD-induced oedema is largely peripheral, may have its origins in changes in haemodynamics, with some contribution from molecules, which regulate cell and tissue permeability (e.g. vascular endothelial growth factor and protein kinase Cbeta), and remains the preponderant manifestation of TZD-induced fluid retention even in those with existing heart failure. Preclinical and pilot clinical data attest to the fact that at least part of the fluid retention derives from a direct effect of TZDs on sodium reabsorption via the renal medullary collecting duct, a mechanism that is sensitive to diuretic agents that have this nephron segment as their site of action, in whole or in part (spironolactone, amiloride and hydrochlorothiazide). Our review suggests various potential clinical strategies by which TZD-induced fluid retention might be effectively monitored and addressed. |
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Authors:
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Janaka Karalliedde; Robin E Buckingham |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Drug safety : an international journal of medical toxicology and drug experience Volume: 30 ISSN: 0114-5916 ISO Abbreviation: Drug Saf Publication Date: 2007 |
Date Detail:
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Created Date: 2007-08-28 Completed Date: 2008-01-08 Revised Date: 2009-11-03 |
Medline Journal Info:
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Nlm Unique ID: 9002928 Medline TA: Drug Saf Country: New Zealand |
Other Details:
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Languages: eng Pagination: 741-53 Citation Subset: IM |
Affiliation:
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Cardiovascular Division, King's College London School of Medicine, Guy's Hospital, King's College London, London, UK. j.karalliedde@kcl.uk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Diabetes Mellitus, Type 2
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complications,
drug therapy Disease Management Diuretics / therapeutic use Edema / chemically induced, drug therapy, epidemiology Heart Failure / chemically induced, epidemiology, prevention & control Humans Hypoglycemic Agents / adverse effects* Obesity / complications, drug therapy PPAR gamma / agonists Thiazolidinediones / adverse effects* |
| Chemical | |
Reg. No./Substance:
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0/Diuretics; 0/Hypoglycemic Agents; 0/PPAR gamma; 0/Thiazolidinediones |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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